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500 | 31,761,962 | Conclusions These techniques do not seem to affect continence by themselves except in minor cases . | Purpose The introduction of transanal endoscopic or minimally invasive surgery has allowed organ preservation for rectal tumors with good oncological results .
Data on functional and quality -of-life ( QoL ) outcomes are scarce and controversial .
This systematic review sought to synthesize fecal continence , QoL , and manometric outcomes after transanal endoscopic microsurgery ( TEM ) or transanal minimally invasive surgery ( TAMIS ) . | Abstract Introduction Transanal endoscopic microsurgery ( TEM ) is a minimal invasive technique for local excision of rectal tumours . The procedure is performed via a rectoscope with a diametre of 4 cm . The aim of this prospect i ve study was to assess both functional outcome and quality of life after TEM . Patients and methods Between 2004 and 2006 , 47 patients were studied prior to and at least 6 months after TEM . Demographics , operative details and post-operative complications were recorded . Functional outcome was determined using the Faecal Incontinence Severity Index ( FISI ) . Quality of life was measured using the EuroQol EQ-5D question naire and the Faecal Incontinence Quality of Life ( FIQL ) score . Results Six months after surgery , median FISI score was found to be decreased ( p < 0.01 ) , depicting an improvement in faecal continence . This improvement was most significant in tumours within 7 cm from the dentate line ( p = 0.01 ) . From the patients ’ perspective , post-operative quality of life was found to be higher ( p < 0.02 ) . A significant improvement was observed in two of the four FIQLS domains ( embarrassment , p = 0.03 ; lifestyle , p = 0.05 ) . The domains of lifestyle , coping and behaviour and embarrassment were correlated with the FISI ( all p < 0.05 ) . Conclusion This study indicates TEM has no deteriorating effect on faecal continence . Moreover , once the tumour has been excised using TEM , quality of life is improved A prospect i ve study of clinical , manometric and proctographic results in 36 patients presenting for transanal endoscopic microsurgery was performed . Anorectal manometry showed no difference in maximal squeeze pressure before and 12 months after operation , but resting pressures were lower after surgery ( mean(s.e.m . ) preoperative 86.1(27.6 ) mmHg versus postoperative 67.2(23.2 ) mmHg , P<0.05 ) . The rectoanal inhibitory reflex was lost in a significant group of patients ( reflex present in 34 of 36 patients before operation and in 27 of 36 12 months after operation , P<0.05 ) . Proctography , manometry and question naire showed preserved function of most modalities 12 months after operation such that if objective function was impaired clinical function was adequate Background : The aim of this study was to evaluate the feasibility , safety , perioperative morbidity , and short-term outcomes of the transanal minimally invasive surgery ( TAMIS ) technique . Methods : This is a descriptive review of prospect ively collected data from 32 consecutive patients who underwent TAMIS procedures in our colorectal unit over a 40-month period . GelPOINT Path port was used in all cases . Demographic data , indications , tumor characteristics , morbidity , and follow-up data were collected . Primary endpoints included feasibility , safety , perioperative morbidity , and resection quality . Results : Fifteen adenomas , 12 carcinomas , 1 gastrointestinal stromal tumor , and 1 neuroendocrine tumor were locally excised . Additionally , 3 pelvic abscesses were drained transanally using the TAMIS port . Mean distance from the anal verge was 5.6 ± 1.5 cm . Early postoperative complications occurred in 22 % , with only one case of major complication ( 3.1 % ) requiring reoperation , and no postoperative mortality . Four carcinomas were understaged ( 33.3 % ) and 1 adenoma overstaged ( 6.7 % ) preoperatively . Three carcinomas were not suspected preoperatively ( 25 % ) . Microscopic positive lateral margin was found in one case , and no affected deep margin was found . Fragmentation rate was 6.9 % , 2 cases , both lesions over 20 cm2 . In cases of fit patients with high-risk carcinomas , 2 underwent immediate salvage surgery and another 2 refused and were treated with adjuvant radiotherapy . With a median follow-up of 26 months , the overall recurrence rate was 10.3 % , 1 adenoma and 2 carcinomas . Conclusion : TAMIS seems to be a safe and reproducible procedure for local excision of well-selected rectal lesions with low morbidity and good functional outcomes Background Transanal minimally invasive surgery ( TAMIS ) is emerging as an alternative to transanal endoscopic microsurgery . Quality of life ( QOL ) and functional outcome are important aspects when valuing a new technique . The aim of this prospect i ve study was to assess both functional outcome and QOL after TAMIS . Methods From 2011 to 2013 , patients were prospect ively studied prior to and at least 6 months after TAMIS for rectal adenomas and low-risk T1 carcinomas using a single-site laparoscopy port . Functional outcome was determined using the Faecal Incontinence Severity Index ( FISI ) . Quality of life was measured using functional [ Faecal Incontinence Quality of Life ( FIQL ) ] and generic ( EuroQol EQ-5D ) question naires . Results The study population consisted of 24 patients 13 men , median age 59 ( range 42–83 ) with 24 tumours [ median distance from the dentate line 8 cm ( range 2–17 cm ) ; median tumour size 6 cm2 ( range 0.25–51 cm2 ) ; 20 adenomas ; 4 low-risk T1 carcinomas ] . Post-operative complications occurred in one patient ( 4 % ; grade IIIb according to Clavien Dindo classification ) . Compared to baseline , FISI remained unaffected ( 9.8 vs 7.3 ; P = 0.26 ) , FIQL remained unaffected , and EuroQol EQ-5D improved ( EQ-VAS : 77 vs 83 ; P = 0.04 ) . Conclusion There was no detrimental effect of TAMIS on anorectal function . Overall QOL was improved after TAMIS , probably due to removal of the tumour , and at 6 months was equal to the general population PURPOSE : The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose ( 5 × 5 Gy ) radiotherapy reduces local failure rates and improves overall survival . This will have an impact on the primary treatment of rectal cancer . This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection . METHODS : A question naire was answered by 92 percent ( 203/220 ) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years . Thirty-two patients were excluded , mainly because of postoperative stomas and dementia , which left 171 for analysis . RESULTS : Median bowel frequency per week was 20 in the irradiated group ( n=84 ) and 10 in the surgery-alone group ( n=87;P<0.001 ) . Incontinence for loose stools ( P<0.001 ) , urgency ( P<0.001 ) , and emptying difficulties ( P<0.05 ) were all more common after irradiation . Sensory functions such as “ discrimination between gas and stool ” and “ ability to safely release flatus ” did not , however , differ between groups . Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction , compared with 10 percent of the surgery-alone group ( P<0.01 ) . CONCLUSIONS : The study indicates that high-dose radiotherapy influences long-term bowel function , thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques BACKGROUND : Currently , the preferred method for local excision of rectal polyps is transanal endoscopic microsurgery , avoiding rectal resection . Transanal minimally invasive surgery is a relatively new technique using a disposable port in combination with conventional laparoscopic instruments . This method is less expensive as compared with transanal endoscopic microsurgery , relatively easy to learn , and available . Despite wide adoption of transanal minimally invasive surgery , to date only a few series on the implementation and use of this technique are reported , and detailed information on the effect of transanal minimally invasive surgery on fecal continence is not available . OBJECTIVE : The purpose of this work was to prospect ively assess the functional outcome after transanal minimally invasive surgery using the Fecal Incontinence Severity Index preoperatively and postoperatively . DESIGN : This was a prospect i ve cohort study . SETTING S : The study was conducted at a large teaching hospital . PATIENTS : Patients included those who underwent transanal minimally invasive surgery between October 2011 and September 2013 . INTERVENTIONS : Transanal minimally invasive surgery was studied . MAIN OUTCOME MEASURES : We measured postoperative surgical and functional results . RESULTS : A total of 37 patients underwent transanal minimally invasive surgery during our study period . Short-term morbidity rate was 14 % , and positive resection margins were reported in 6 cases ( 16 % ) ; in 1 of these patients , a local recurrence was observed . Overall , there was a significant decline in preoperative and postoperative Fecal Incontinence Severity Index scores ( p = 0.02 ) , indicating an improvement in anorectal function after transanal minimally invasive surgery for patients with impaired preoperative continence . Seventeen patients ( 49 % ) had impaired continence before transanal minimally invasive surgery ( mean Fecal Incontinence Severity Index score = 21 ) . Continence improved in 15 ( 88 % ) of these patients after surgery ; no change was observed in 1 patient ( 6 % ) , and continence further decreased in another . In addition , 18 patients ( 51 % ) had normal preoperative continence ( Fecal Incontinence Severity Index score = 0 ) , of which 83 % had no change in functionality , and continence decreased in 3 . LIMITATIONS : No quality of life was measured . CONCLUSIONS : Short-term functional results of transanal minimally invasive surgery for rectal polyps are excellent and comparable to functional results using the dedicated transanal endoscopic microsurgery equipment . More research on outcome after transanal minimally invasive surgery is needed to assess morbidity rates and oncologic clearance Abstract PURPOSE : There is accumulating evidence , both quantitative and qualitative , that pelvic irradiation adversely affects anorectal function . However , histologic evidence of sphincter injury has not been demonstrated . This study was design ed to perform histologic assessment of collagen deposition and nerve alteration in the internal anal sphincters of rectal cancer patients who underwent abdominoperineal resection after adjuvant chemoradiation therapy and to correlate the degree of histologic changes with the time interval between chemoradiotherapy and abdominoperineal resection . METHODS : Anal canal specimens were prospect ively collected in patients undergoing abdominoperineal resection . Representative slides were cut transversely at the level of the dentate line . Using trichrome and S-100 protein staining , a single pathologist blinded to the patients ’ treatment assessed collagen deposition and nerve fiber densities in the internal anal sphincter , respectively . RESULTS : Twelve patients received radiation for rectal cancer ( chemoradiotherapy group ) and six were treated by surgery alone , including four patients with rectal cancer ( 1 leiomyosarcoma ) and two with Crohn ’s disease ( control group ) . There was a trend toward increased fibrosis ( replacement of > 10 percent of normal structures by collagen ) and nerve density in the chemoradiotherapy group compared with the control group ( P = 0.08 and P = 0.05 , respectively ) . Nerve density significantly increased as chemoradiotherapy to abdominoperineal resection interval increased ( P = 0.04 ) . CONCLUSIONS : Pelvic irradiation results in damage to the myenteric plexus of the internal anal sphincter of patients with rectal cancer ; these alterations seem to be time-dependent . A trend toward increased collagen deposition also was observed . Together , these results provide a morphologic basis , which concurs to previously described physiologic and clinical alterations in the anal sphincter of patients irradiated for rectal cancer PURPOSE Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision ( TME ) . This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME . Also , hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment . PATIENTS AND METHODS Long-term morbidity was assessed in patients from the prospect i ve r and omized TME trial , which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer . Dutch patients without recurrent disease were sent a question naire . RESULTS Results were obtained from 597 patients , with a median follow-up of 5.1 years . Stoma function , urinary function , and hospital treatment rates did not differ significantly between the treatment arms . However , irradiated patients , compared with nonirradiated patients , reported increased rates of fecal incontinence ( 62 % v 38 % , respectively ; P < .001 ) , pad wearing as a result of incontinence ( 56 % v 33 % , respectively ; P < .001 ) , anal blood loss ( 11 % v 3 % , respectively ; P = .004 ) , and mucus loss ( 27 % v 15 % , respectively ; P = .005 ) . Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone . CONCLUSION Although preoperative short-term radiotherapy for rectal cancer results in increased local control , there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone . Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME . Future strategies should be aim ed at selecting patients for radiotherapy who are at high risk for local failure PURPOSE This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy ( SCRT ) followed by transanal endoscopic microsurgery ( TEM ) for T1-T2 N0 extraperitoneal rectal cancer . Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer . METHODS AND MATERIAL S We planned a prospect i ve pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later ( SCRT-TEM ) . Safety , efficacy , and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy ( LCRT ) followed by TEM ( LCRT-TEM ) , TEM alone , or laparoscopic rectal resection with total mesorectal excision ( TME ) at our institution . RESULTS The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM . Median time between SCRT and TEM was 7 weeks ( range : 4 - 10 weeks ) . Although no preoperative complications occurred , rectal suture dehiscence was observed in 7 patients ( 50 % ) at 4 weeks follow-up , associated with an enterocutaneous fistula in the sacral area in 2 cases . One patient required a colostomy . Quality of life at 1-month follow-up , according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score , was significantly worse in SCRT-TEM patients than in LCRT-TEM patients ( P=.0277 ) or TEM patients ( P=.0004 ) , whereas no differences were observed with TME patients ( P=.604 ) . At a median follow-up of 10 months ( range : 6 - 26 months ) , we observed 1 ( 7 % ) local recurrence at 6 months that was treated with abdominoperineal resection . CONCLUSIONS SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous fistula , compared to TEM alone and TEM following LCRT , which forced us to stop the study Abstract Background and aims : This study evaluated the effect of transanal endoscopic microsurgery ( TEM ) on anorectal sphincter functions and determined the risk factors for anorectal dysfunctions ( including incontinence ) . Patients and methods : A study group of 33 patients with small , mobile rectal tumors ( adenoma and carcinoma ) located up to 12 cm from the anal verge underwent anorectal motility studies ( using pull-through anorectal manometry and rectal barostat ) and endoanal ultrasound prior to surgery and 3 weeks and 6 months after TEM ; controls were 20 healthy volunteers . Results : Resting and squeeze anal pressures were reduced 3 weeks after TEM . Resting anal pressure remained reduced 6 months after surgery ; the changes were related to low preoperative levels and to the internal anal sphincter defects rather than to the procedure duration or the type of surgery . High-pressure zone length and vector volume were decreased 3 weeks after TEM and restored 6 months later . Rectoanal inhibitory reflex , reflex sphincter contraction , rectoanal pressure gradients , threshold and maximal tolerable volume of rectal sensitivity , and compliance were significantly changed 3 weeks after TEM ; only rectal wall compliance remained low at 6 months . The rectoanal inhibitory reflex , reflex sphincter contraction , rectal sensitivity , and compliance were related to the extent and type of excision ( partial or full thickness ) . Anal ultrasound revealed internal anal sphincter defects in 29 % of patients studied 3 weeks after TEM . Only 76 % of patients were fully continent . Disturbed anorectal function ( including partial fecal incontinence ) was observed in up to 50 % of patients at 3 weeks . Partial and moderate anorectal dysfunction was found in 21 % patients 6 months after surgery . The main risk factors of anorectal dysfunctions following TEM included : postoperative internal anal sphincter defects , low preoperative resting anal pressure , disturbed rectoanal coordination , extent ( > 50 % of wall circumference ) and the depth ( full thickness ) of tumor excision . Conclusion : TEM has a relevant but temporary effect on anorectal motility . As a result of TEM procedures 21 % of the patients had disturbed anorectal functions , mostly due to the extent or depth of tumor excision ( influencing rectal compliance and rectoanal coordination ) , and to the sphincter defects lowering resting anal pressure . Preoperative anorectal motility studies and anal ultrasound allow the identification of patients with the risk of postoperative anorectal dysfunctions BACKGROUND : Since its inception in 2009 , transanal minimally invasive surgery has been used increasingly in the United States and internationally as an alternative to local excision and transanal endoscopic microsurgery for local excision of neoplasms in the distal and mid rectum . Despite its increasing acceptance , the clinical benefits of transanal minimally invasive surgery have not yet been vali date d. OBJECTIVE : The aim of this study is to assess the adequacy of transanal minimally invasive surgery for the local excision of benign and malignant lesions of the rectum . DESIGN : This is a retrospective analysis of consecutive patients who underwent transanal minimally invasive surgery for local excision of neoplasms at a single institution . SETTING S : The study was conducted by a single group of colorectal surgeons at a tertiary referral center . PATIENTS : Eligible patients with early-stage rectal cancer and benign neoplasms were offered transanal minimally invasive surgery as a means for local excision . Data from these patients were collected prospect ively in a registry . MAIN OUTCOME MEASURES : The primary outcome measures included the feasibility of transanal minimally invasive surgery for local excision , resection quality , and short-term clinical results . RESULTS : Fifty patients underwent transanal minimally invasive surgery between July 2009 and December 2011 . Twenty-five benign neoplasms , 23 malignant lesions , and 2 neuroendocrine tumors were excised . All lesions were excised using transanal minimally invasive surgery without conversion to an alternate transanal platform . The average length of stay was 0.6 days ( range , 0–6 ) , and 68 % of patients were discharged on the day of surgery . The average distance from the anal verge was 8.1 cm ( range , 3–14 cm ) . All lesions were excised completely with only 2 fragmented specimens ( 4 % ) . All specimens were removed with grossly negative margins , although 3 ( 6 % ) were found to have microscopically positive margins on final pathology . There were 2 recurrences ( 4 % ) at 6- and 18-month follow-up . Early complications occurred in 3 patients ( 6 % ) . No long-term complications were observed at a median follow-up of 20 months . LIMITATIONS : The study was limited by its retrospective nature and midterm follow-up . CONCLUSIONS : Transanal minimally invasive surgery is an advanced transanal platform that provides a safe and effective method for resecting benign neoplasms , as well as carefully selected , early-stage malignancies of the mid and distal rectum PURPOSE Local excision is a commonly used technique for many benign and selected malignant rectal lesions . Compared with radical resection , it is associated with decreased morbidity and mortality and improved functional results . Transanal endoscopic microsurgery is gaining popularity because of its ability to access the upper rectum and its precise excision techniques . However , the functional consequences have not been extensively studied . METHODS All patients subject to transanal endoscopic microsurgery prospect ively completed preoperative and postoperative ( 6 weeks ) surveys including Fecal Incontinence Severity Index , Fecal Incontinence Quality of Life , number of bowel movements per 24 hours , and ability to defer defecation . All data were collected by an independent research coordinator . Demographics , operative details , and complications were also collected prospect ively . RESULTS Forty-one patients successfully underwent transanal endoscopic microsurgery . Fourteen patients had malignant lesions and 27 had benign lesions . Two patients required abdominoperineal resection based on postoperative diagnosis . Thirty-nine patients have completed follow-up and were available for review . Mean length of surgery was 64 minutes and length of stay was 0.9 day . Average distance from the anal verge to the proximal tumor margin was 11.4 cm and mean tumor size was 8.75 cm . Twenty-three patients had full-thickness excision with primary closure , ten had full-thickness excision without closure , five had partial-thickness excision , one had an excision of a mass in the anovaginal septum , and one had resection of an anastomotic stricture . Each patient served as his own control . Preoperative and postoperative number of bowel movements per 24 hours were 2.0 and 2.0 , respectively . Preoperative vs. postoperative urgency ( ability to defer defecation less than ten minutes ) was unchanged . Mean preoperative and postoperative Fecal Incontinence Severity Index scores were 2.4 ( range , 0–43 ) and 2.4 ( range , 0–17 ) , respectively ( higher scores indicate worse function ) . In addition , the four parameters measured by the Fecal Incontinence Quality of Life survey were unchanged when preoperative and postoperative data were compared . CONCLUSIONS Transanal endoscopic microsurgery allows precise excision of tumors throughout the rectum . However , it involves inserting a 40-mm-diameter operating proctoscope and significant operating times . Despite this , as measured by ability to defer defecation , number of bowel movements per 24 hours , Fecal Incontinence Severity Index , and Fecal Incontinence Quality of Life survey , transanal endoscopic microsurgery has no detrimental affect on fecal continence Purpose The st and ard treatment of rectal adenocarcinoma is total mesorectal excision ( TME ) , in many cases requires a temporary or permanent stoma . TME is associated with high morbidity and genitourinary alterations . Transanal endoscopic microsurgery ( TEM ) allows access to tumors up to 20 cm from the anal verge , achieves minimal postoperative morbidity and mortality rates , and does not require an ostomy . The treatment of T2 , N0 , and M0 cancers remains controversial . Preoperative chemoradiotherapy ( CRT ) in association with TEM reduces local recurrence and increases survival . The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME . Methods Prospect i ve , multicenter , r and omized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size , staged as T2 or T3-superficial N0-M0 . Patients will be r and omized to two areas : CRT plus TEM or radical surgery ( TME ) . Postoperative morbidity and mortality will be recorded and patients will complete the quality of life question naires before the start of treatment , after CRT in the CRT/TEM arm , and 6 months after surgery in both arms . The estimated sample size for the study is 173 patients . Patients will attend follow-up controls for local and systemic relapse . Conclusions This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2–3s , N0 , M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME).Trial registration Clinical Trials.gov identifier : NCT01308190 . Número de registro del Comité de Etica e Investigación Clínica ( CEIC ) del Hospital universitario Parc Taulí : TAU-TEM-2009 - 01 BACKGROUND / AIMS Most clinical research addresses the technological advances and oncological outcomes of transanal endoscopic microsurgery . Our aim was to examine the functional results . METHODOLOGY From August 1999 to November 2000 , 22 Taiwanese patients ( 14 men , 8 women ; median age , 68 years ) undergoing transanal endoscopic microsurgery were prospect ively examined . Functional question naires and anorectal manometry were assessed before surgery and at 2 weeks , 6 weeks , 3 months , and 1 year . RESULTS The median distance from the anal verge to the tumor was 10 cm . The median tumor diameter was 2.0 cm . The median duration of surgery was 120 minutes . No surgical mortality or morbidity and no local recurrence occurred during a median follow-up of 23 months . The mean stool frequency and consistency were significantly better at 3 months after surgery than before surgery . The maximal resting pressure significantly decreased after surgery . The maximal contraction pressure and maximal tolerated volume were significantly lower at 2 and 6 weeks than before surgery ; these values recovered at 1 year . CONCLUSIONS Transanal endoscopic microsurgery is safe for the cure of benign tumors and the palliative excision of malignant tumors in middle and upper rectum . Anorectal function was preserved and improved , though some anorectal manometric parameters changed over time AIM To evaluate the impact of Transanal Endoscopic Microsurgery ( TEM ) on anorectal function , using clinical and manometric assessment s. To identify subgroups likely to develop incontinence after TEM , by stratifying the sample . METHOD Descriptive , prospect i ve study . Between December 2004 and May 2011 , 222 patients were operated on at our hospital , of whom 21 were excluded from the study . Patients underwent anal manometry and answered a clinical incontinence question naire ( the Wexner scale ) prior to surgery , one month post-surgery , and then at four months post-surgery . RESULTS There were no statistically significant differences between preoperative Wexner question naire scores and values at one month and four months post-surgery . Preoperative baseline pressure ( BP ) values were 64 mmHg±26.18 , falling to 44.26 mmHg±20.11 at one month and to 48.86 mmHg±21.14 at four months . Voluntary Contraction Pressure ( VCP ) reached preoperative values of 200.49 mmHg±88.85 , falling to 169.5 mmHg±84.95 and to 173.6±79 at four months . The differences in BP and VCP were statistically significant . The sample was stratified in order to identify subsets susceptible to incontinence after surgery , but no at-risk subgroups were found . Multivariate analysis did not detect any predictors of incontinence . CONCLUSION The sustained , controlled anal dilatation produced with TEM caused statistically significant decreases in VCP and BP one month and four months after surgery . However , the Wexner question naire scores did not show any association with clinical incontinence . No predictors of postoperative incontinence were observed . We conclude that TEM is a safe technique and does not affect continence Purpose Preoperative radiotherapy improves local control in rectal cancer treatment , but there are few reports on the influence of radiotherapy on anorectal function . The aim of the present study was to assess late effects of short-course , high-dose radiotherapy on anorectal function after low anterior resection for rectal cancer . Methods Sixty-four patients , r and omized within the Stockholm Radiotherapy Trials and operated on with low anterior resection with or without preoperative radiotherapy ( mean , 14 years ) , previously were followed up with quality -of-life question naires , clinical examination , anorectal manometry , and endoanal ultrasound . Twenty-one patients had received preoperative radiotherapy of the rectum and 43 patients had been treated with surgery alone . Results Impaired anorectal function was common after low anterior resection for rectal cancer and the risk was increased after radiotherapy . Irradiated patients had significantly more symptoms of fecal incontinence ( 57 vs. 26 percent , P = 0.01 ) , soiling ( 38 vs. 16 percent , P = 0.04 ) , and significantly more bowel movements per week ( 20 vs. 10 , P = 0.02 ) . At anorectal manometry , irradiated patients had significantly lower resting ( 35 mmHg vs. 62 mmHg , P < 0,001 ) and squeeze pressures ( 104 mmHg vs. 143 mmHg , P = 0.05 ) . At endoanal ultrasound , irradiated patients had significantly more scarring of the anal sphincters ( 33 vs. 13 percent , P = 0.03 ) . There were no significant differences in quality -of-life scores between irradiated and nonirradiated patients ; however , patients with anal incontinence had significantly lower quality -of-life scores compared to continent patients . Conclusions Short-course radiotherapy , including the anal sphincters , impairs anorectal function and increases gastrointestinal symptoms permanently when the anal sphincters are irradiated Laparoscopic colorectal surgery ( LCS ) was first described in the 1990s and for the most part has become the st and ard of care for colorectal surgery . Robotic-assisted colorectal surgery ( RACS ) was described around the year 2000 , and advocates argue that it overcomes many issues associated with laparoscopic surgery , particularly in surgery for rectal cancer . More recently , the bottom-up minimally invasive approach , transanal total mesorectal excision ( TaTME ) , for rectal surgery has gained popularity , and it has perceived advantages over laparoscopic rectal surgery . Minimally invasive surgery has been associated with some short-term benefits , including reduced bleeding and postoperative pain , and better cosmetic outcomes . Despite this , the debate on oncologic outcomes when compared with open surgery is still ongoing [ 1–3 ] . The benefits of one minimally invasive approach over the others form the subject of further debate , and as much of this is driven by proponents of an individual technique , choosing the most appropriate technique can be difficult [ 1 , 2 ] . Despite the enthusiasm of the proponents , many other factors play a part in the choice of technique and these can be broadly described as those related to the patient , surgeon and individual hospital or a country . We compared LCS , RACS and TaTME/TAMIS using the following criteria : ( 1 ) number of studies published in three time frames ( I = within the first 2 years after acceptance of the technique ; II = during the subsequent 3 years ; III = 3 years after II , if available ) ; ( 2 ) number of involved patients ; ( 3 ) predicted/actual trends . We search ed PubMed and only included r and omized controlled trials , clinical trials , observational , case – control and cohort studies ( time frames : laparoscopy — I : 1993–1994 , II : 1995–1997 , III : 1997–2000 ; robotically assisted — I : Dec 2004–2006 , II : 2007–2009 , III : 2010–2012 ; transanal proctectomy — I : 2013–2014 , II : 2015–2016 ) . The findings are summarized in Figs. 1 and 2 . In the early years , the USA contributed majority of publications related to LCS , with China contributing at the lower end of the spectrum . By the II time frame , there were more contributions from Western Europe , Japan and Australia . In the III time frame , there was a notable increase in reporting on LCS with more contributions from the USA and Western Europe as well as the UK and Sc and inavian countries , in addition to Japan , Australia and China . For RACS , in the early time period there were a few manuscripts from the USA and Europe . During the subsequent time frame , reports from the USA continued to increase , whereas there was less reporting from European countries with the exception of the UK . There was also more reporting of robotic surgery from South Korea , while the enthusiasm from Europe was not as strong as that for LCS . The USA and South Korea appear to be leading the charge in this regard . This begs the question whether this is mainly related to the cost of the procedure . The concept of TaTME originated in the USA with some individuals promoting the technique within Europe . During the II time frame , adoption of TaTME mushroomed to include many continental European countries , while adoption of the technique was being introduced rapidly in the USA and UK . Figure 2 shows the trends of LCS , RACS and TaTME in the different time frames . LCS had a gradual but constant increase over time , with an expected further increase probably as experience was disseminated by training a new generation of surgeons . RACS growth was slower during the second time frame , but increased considerably during the third , with an almost threefold increase . TaTME trend sits between these two , in * J. Warusavitarne Purpose Transanal minimally invasive surgery ( TAMIS ) is gaining worldwide popularity as an alternative for the transanal endoscopic microsurgery ( TEMS ) method for the local excision of rectal polyps and selected neoplasms . Data on patient reported outcomes regarding short-term follow-up are scarce ; data on functional outcomes for long-term follow-up is non-existent . Methods We used the fecal incontinence severity index ( FISI ) to prospect ively assess the fecal continence on the intermediate-term follow-up after TAMIS . The primary outcome measure is postoperative fecal continence . Secondary outcome measures are as follows : perioperative and intermediate-term morbidity . Results Forty-two patients ( m = 21:f = 21 ) , median age 68.5 ( range 34–94 ) years , were included in the analysis . In four patients ( 9.5 % ) , postoperative complications occurred . The median follow-up was 36 months ( range 24–48 ) . Preoperative mean FISI score was 8.3 points . One year after TAMIS , mean FISI score was 5.4 points ( p = 0.501 ) . After 3 years of follow-up , mean FISI score was 10.1 points ( p = 0.01 ) . Fecal continence improved in 11 patients ( 26 % ) . Continence decreased in 20 patients ( 47.6 % ) ( mean FISI score 15.2 points , [ range 3–31 ] ) . Conclusions This study found that the incidence of impaired fecal continence after TAMIS is substantial ; however , the clinical significance of this deterioration seems minor . The present data is helpful in acquiring informed consent and emphasizes the need of proper patient information . Functional results seem to be comparable to results after TEMS . Furthermore , we confirmed TAMIS is safe and associated with low morbidity Background : Transanal endoscopic microsurgery is a minimally invasive technique that allows full-thickness resection and suture closure of the defect for large rectal adenomas , selected low-risk rectal cancers , or small cancers in patients who have a high risk for major surgery . Our aim , in the given prospect i ve study was to report our initial clinical experience with TAMIS , and to evaluate its effects on postoperative anorectal functions . Material s and Methods : In 10 patients treated with TAMIS for benign and malignant rectal tumors , preoperative and postoperative anorectal function was evaluated with anorectal manometry and Clevel and Clinic Incontinence Score . Results : The mean distance of the tumors from the anal verge was 5.6 cm , and mean tumor diameter was 2.6 cm . All resection margins were tumor free . There was no difference in preoperative and 3-week postoperative anorectalmanometry findings ; only mean minimum rectal sensory volume was lower at 3 weeks after surgery . The Clevel and Clinic Incontinence Score was normal in all patients except one which resolved by 6 weeks after surgery . The mean postoperative follow-up was 28 weeks without any recurrences . Conclusion : Transanal minimally invasive surgery is a safe and effective procedure for treatment of rectal tumors and can be performed without impairing anorectal functions PURPOSE : Compared with traditional operations , superior results after transanal endoscopic microsurgery ( TEM ) for rectal tumors have been demonstrated in terms of morbidity and mortality . However , no data were available on functional outcome after TEM . We , therefore , studied 42 patients who were undergoing TEM . METHODS : Patients were examined by anorectal manometry and participated in a st and ardized interview preoperatively and three months and one year after surgery . RESULTS : Anorectal function as assessed by manometry was impaired three months after surgery but improved again during the first postoperative year . In parallel , some patients complained of impaired continence or defecation disorders in the interview three months postoperatively . These functions improved during the first year after surgery , too . CONCLUSIONS : Correct comparison of our results with functional outcome after anterior rectal resection is impossible . We feel , however , that functional results after TEM are likely to be superior to those after anterior resection for rectal tumors AIM Endoluminal Loco-Regional Resection ( ELRR ) by Transanal Endoscopic Microsurgery ( TEM ) may be considered a valid alternative surgical treatment in patients with rectal cancer . Aim of this study is to evaluate the short and medium term Quality of Life ( QoL ) from prospect ively collected data in patients who underwent ELRR by TEM . MATERIAL OF STUDY From May 2010 to June 2013 , 31 patients with iT1-iT2-iT3N0 rectal cancer were enrolled in this study . Patients with T1 rectal cancer underwent ELRR by TEM . Patients with iT2-iT3 rectal cancer underwent neoadjuvant radio-chemoterapy ( n- RCT ) before surgery . QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 question naires before surgery and 1 , 6 , and 12 months after surgery . RESULTS Mean distance from the anal verge was 5.4 cm ( range 1 - 10 ) . Mean operative time was 145.8 minutes ( range 60 - 300 ) . Pathological staging was as follows : pT0N0 ( 6 ) , pT1N0 ( 18 ) , pT2N0 ( 7 ) . At 1 month after surgery , in QLQC30 question naire , significant worsening was observed in Global Health Status ( p=0.0028 ) , Physical Functioning ( p=0.0016 ) , Role Functioning ( p=0.0004 ) , Fatigue ( p=0.0024 ) , Pain ( p=0.0003 ) and Dyspnoea ( p=0.0192 ) . In QLQCR38 question naire significant worsening at 1 month was observed in Defecation Problems ( p=0.0005 ) and Weight Loss ( p=0.0008 ) . At six and twelve months after surgery , no significant differences were observed in QLQ-C30 and in QLQCR38 question naires . DISCUSSION QoL evaluation showed worsening results at 1 month after ELRR by TEM , in QLQ-C30 and in QLQCR38 question naires . CONCLUSIONS At 6 and 12 months after surgery , no significant differences in QoL as compared to preoperative status were observed Benign tumours of the rectum may be destroyed by diathermy or cryotherapy , or may be locally excised using a urological resectoscope or by more invasive techniques such as the York‐Mason trans‐sphincteric resection1,2 . Transanal endoscopic microsurgical excision of such tumours has the advantage of allowing a magnified view during excision , which enables resection of an unfragmented specimen with clear margins3 . More proximal lesions can also be resected . However , the technique requires a prolonged period of anal dilatation using a 4‐cm diameter sigmoidoscope , which may compromise sphincter function4,5 . The aim of this prospect i ve study was to examine sphincter function before and after transanal endoscopic microsurgical excision of rectal tumours |
501 | 31,952,507 | Conclusions The results of this study show that compared to conventional fractionated radiotherapy , hypofractionated radiotherapy is not significantly different with respect to efficacy or toxicity in postmastectomy breast cancer . | Purpose To compare the efficacy and toxicity of hypofractionated radiotherapy versus conventional fractionated radiotherapy in postmastectomy breast cancer using meta- analysis . | Summary Background The international st and ard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2·0 Gy over 5 weeks , but there is a long history of non-st and ard regimens delivering a lower total dose using fewer , larger fractions ( hypofractionation ) . We aim ed to test the benefits of radiotherapy schedules using fraction sizes larger than 2·0 Gy in terms of local-regional tumour control , normal tissue responses , quality of life , and economic consequences in women prescribed post-operative radiotherapy . Methods Between 1999 and 2001 , 2215 women with early breast cancer ( pT1 - 3a pN0 - 1 M0 ) at 23 centres in the UK were r and omly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy over 5 weeks or 40 Gy in 15 fractions of 2·67 Gy over 3 weeks . Women were eligible for the trial if they were aged over 18 years , did not have an immediate reconstruction , and were available for follow-up . R and omisation method was computer generated and was not blinded . The protocol -specified principal endpoints were local-regional tumour relapse , defined as reappearance of cancer at irradiated sites , late normal tissue effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . Findings 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group . After a median follow up of 6·0 years ( IQR 5·0–6·2 ) the rate of local-regional tumour relapse at 5 years was 2·2 % ( 95 % CI 1·3–3·1 ) in the 40 Gy group and 3·3 % ( 95 % CI 2·2 to 4·5 ) in the 50 Gy group , representing an absolute difference of −0·7 % ( 95 % CI −1·7 % to 0·9%)—ie , the absolute difference in local-regional relapse could be up to 1·7 % better and at most 1 % worse after 40 Gy than after 50 Gy . Photographic and patient self- assessment s indicated lower rates of late adverse effects after 40 Gy than after 50 Gy . Interpretation A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the st and ard schedule of 50 Gy in 25 fractions OBJECTIVE Concomitant chemo-radiotherapy after modified radical mastectomy for breast cancer is an effective means of achieving high survival rates . In this study different radiotherapy optimization regimens are compared to assess their effectiveness and toxicity rates . PATIENTS AND METHODS 112 patients with modified radical mastectomy participated , and were r and omly assigned to one of three groups , all receiving adjuvant chemotherapy for 4 - 6 weeks prior to radiotherapy : group A received intensity modulated radiotherapy ( radiation dose ( DT ) 50 Gy , 2.0 Gy/fraction , 25 times , during the course of 33 - 35 days ) ; group B received concurrent radio chemotherapy and intensity modulated radiotherapy ; and group C adopted concurrent radio chemotherapy and hypofractionation ( DT of 42.56 Gy , 2.66Gy/fraction , 16 times , during the course of 22 - 24 days ) with 37 cases . The occurrence of acute and chronic radiation injuries , the cancer recurrence and the survival rates were compared , and a dose volume histogram ( DVH ) was created . RESULTS The total prevalence and survival rates of Group C were significantly better than those of the other two groups ( p ≤ 0.05 ) ; in spite of the fact that the local recurrence and distant metastasis rates separately were all statistically the same ( p ≥ 0.05 ) . Also , the total radiation injury occurrence of group C was significantly lower ( p < 0.05 ) ; but no significant differences were found when singling out acute and chronic injury occurrences or injury severity between the three groups . The values of V5 , V10 , V20 and V30 increased gradually in all of the groups , and V5 and V10 in Group C were higher than those in the other two groups , but the comparison between V20 and V30 yielded no statistically significant differences . CONCLUSIONS Based on these results , the concurrence of hypo-fractionation radiotherapy and chemotherapy may be an effective and safe approach for cancer treatment after modified radical mastectomy , and larger studies are warranted given the convenience of the method BACKGROUND 5-year results of the UK St and ardisation of Breast Radiotherapy ( START ) trials suggested that lower total doses of radiotherapy delivered in fewer , larger doses ( fractions ) are at least as safe and effective as the historical st and ard regimen ( 50 Gy in 25 fractions ) for women after primary surgery for early breast cancer . In this prespecified analysis , we report the 10-year follow-up of the START trials testing 13 fraction and 15 fraction regimens . METHODS From 1999 to 2002 , women with completely excised invasive breast cancer ( pT1 - 3a , pN0 - 1 , M0 ) were enrolled from 35 UK radiotherapy centres . Patients were r and omly assigned to a treatment regimen after primary surgery followed by chemotherapy and endocrine treatment ( where prescribed ) . R and omisation was computer-generated and stratified by centre , type of primary surgery ( breast-conservation surgery or mastectomy ) , and tumour bed boost radiotherapy . In START-A , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41·6 Gy or 39 Gy in 13 fractions over 5 weeks . In START-B , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks . Eligibility criteria included age older than 18 years and no immediate surgical reconstruction . Primary endpoints were local-regional tumour relapse and late normal tissue effects . Analysis was by intention to treat . Follow-up data are still being collected . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . FINDINGS START-A enrolled 2236 women . Median follow-up was 9·3 years ( IQR 8·0 - 10·0 ) , after which 139 local-regional relapses had occurred . 10-year rates of local-regional relapse did not differ significantly between the 41·6 Gy and 50 Gy regimen groups ( 6·3 % , 95 % CI 4·7 - 8·5 vs 7·4 % , 5·5 - 10·0 ; hazard ratio [ HR ] 0·91 , 95 % CI 0·59 - 1·38 ; p=0·65 ) or the 39 Gy ( 8·8 % , 95 % CI 6·7 - 11·4 ) and 50 Gy regimen groups ( HR 1·18 , 95 % CI 0·79 - 1·76 ; p=0·41 ) . In START-A , moderate or marked breast in duration , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 39 Gy group than in the 50 Gy group . Normal tissue effects did not differ significantly between 41·6 Gy and 50 Gy groups . START-B enrolled 2215 women . Median follow-up was 9·9 years ( IQR 7·5 - 10·1 ) , after which 95 local-regional relapses had occurred . The proportion of patients with local-regional relapse at 10 years did not differ significantly between the 40 Gy group ( 4·3 % , 95 % CI 3·2 - 5·9 ) and the 50 Gy group ( 5·5 % , 95 % CI 4·2 - 7·2 ; HR 0·77 , 95 % CI 0·51 - 1·16 ; p=0·21 ) . In START-B , breast shrinkage , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group . INTERPRETATION Long-term follow-up confirms that appropriately dosed hypofractionated radiotherapy is safe and effective for patients with early breast cancer . The results support the continued use of 40 Gy in 15 fractions , which has already been adopted by most UK centres as the st and ard of care for women requiring adjuvant radiotherapy for invasive early breast cancer . FUNDING Cancer Research UK , UK Medical Research Council , UK Department of Health Purpose Conventionally fractionated postmastectomy radiation therapy ( PMRT ) takes approximately 5 to 6 weeks . Data supporting hypofractionated PMRT is limited . We prospect ively evaluated a short course of hypofractionated PMRT , in which therapy was completed in 15 treatment days . Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes , followed by an optional mastectomy scar boost of four fractions of 3.33 Gy . Our primary end point was freedom from any grade 3 or higher toxicities . We incorporated early stopping criteria on the basis of predefined toxicity thresholds . Results We enrolled 69 women with stage II to IIIa breast cancer , of whom 67 were eligible for analysis . After a median follow-up of 32 months , there were no grade 3 toxicities . There were 29 reported grade 2 toxicities , with grade 2 skin toxicities being the most frequent ( 16 of 67 ; 24 % ) . There were two patients with isolated ipsilateral chest wall tumor recurrences ( 2 of 67 ; crude rate , 3 % ) . Three-year estimated local recurrence-free survival was 89.2 % ( 95 % CI , 0.748 to 0.956 ) . The 3-year estimated distant recurrence-free survival was 90.3 % ( 95 % CI , 0.797 to 0.956 ) . Forty-one patients had chest wall reconstructions ; three had exp and ers removed for infection before radiation therapy . The total rate of implant loss or failure was 24 % ( 9 of 38 ) , and the unplanned surgical correction rate was 8 % ( 3 of 38 ) , for a total complication rate of 32 % . Conclusion To our knowledge , our phase II prospect i ve study offers one of the shortest courses of PMRT reported , delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost . We demonstrated low toxicity and high local control with this schedule . On the basis of our data , we have design ed a cooperative group phase III prospect i ve , r and omized trial of conventional versus hypofractionated PMRT that will activate soon Introduction : The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients . Methods : 3 irradiation schedules were analyzed : 48.30 Gy in 21 fractions ( group A , n = 60 ) , 42.56 Gy in 16 fractions ( group B , n = 27 ) and 50 Gy in 25 fractions ( group C , n = 30 ) of the front chest wall . All groups were also treated with a supraclavicular field , with 39.10 Gy in 17 fractions ( group A ) , 37.24 Gy in 14 fractions ( group B ) or 45 Gy in 25 fractions ( group C ) . Results : No local recurrences were noted in any group during 36 months of follow-up . Acute skin toxicity presented in all groups , with 58.3 % , 70.4 % and 60 % of grade I ; 35 % , 25.9 % and 40 % of grade II ; 6.7 % , 3.7 % and 0 % of grade III being seen in groups A , B and C , respectively . Late skin toxicity was noted only as grade I in 16.7 % , 25.9 % and 26.7 % of groups A , B and C , respectively . No significant difference was noted among all groups for either acute or late skin toxicity , or for radio-pneumonitis ( chi2 test , p > 0.05 ) . Conclusion : All schedules were equally effective with equivalent toxicity . A prospect i ve r and omized study is needed to confirm our results Background Several r and omized trials and meta-analyses confirmed a wide benefit of radiotherapy ( RT ) , both after breast conserving surgery ( BCS ) and mastectomy . However , many elderly women do n't receive RT . Hypofractionated ( HF ) RT allows « simplified » and more accessible treatments with equivalent results to classic RT in three large r and omized trials . However , there are few available data on HF-RT for nodal irradiation , as well as for the boost . Methods We evaluated patients treated for IBC by HF-RT between 2004 and 2012 in two regional cancer centres . We used an original scheme delivering 45 Gy in 15 fractions three times a week , both after BCS or mastectomy , with or without nodal irradiation . After BCS , a 9 Gy boost in 3 fractions was delivered . Local , regional and distant recurrences were assessed , as well as acute and late cutaneous , cardiac or pulmonary toxicities . Results 205 patients were analysed , 116 after BCS ( 57 % ) and 89 after mastectomy ( 43 % ) . Median age was 81 years ( range : 52 - 91 ) ; 44 % had axillary nodal involvement ( pN+ ) . The Nottingham Prognostic Index ( NPI ) scored 0 , 1 , 2 and 3 in 10 % , 27 % , 44 % and 19 % of the cases . A nodal HF-RT was delivered in 65 patients ( 32 % ) and boost in 98 patients ( 84 % of BCS ) by 9 Gy/3 fr scheme . Fifty ( 24 % ) patients underwent chemotherapy and 156 ( 75 % ) hormonal treatment . With a 49-month median follow-up , 3/116 ( 2.6 % ) patients and 4/89 ( 4.5 % ) had local recurrence ( LR ) after BCS and mastectomy , respectively . The overall 5-year LR rate was 4.4 % . In univariate and multivariate analysis , LR risk factors were : high NPI ( HR 5.46 ; p = 0.028 ) , and triple negative tumour ( HR 9.78 ; p = 0.006 ) . Only 8 ( 4.5 % ) patients had grade III skin toxicity ; 29 ( 14 % ) late fibrosis and 16 ( 8 % ) telangiectasia . No pulmonary or cardiac toxicity was observed . Conclusion Our HF-RT scheme ( with or without nodal irradiation ) confirms in elderly patients the data from r and omized trials , both after BCS or mastectomy . Toxicity seems very acceptable but requires a longer follow-up . A larger evaluation is still ongoing in several other centres in France Purpose To evaluate the efficacy and safety of hypofractionated whole-breast irradiation ( HF-WBI ) compared with conventionally fractionated ( CF ) WBI . Material s and methods Patients with early breast cancer ( stages 0–II and <3 positive lymph nodes ) who had undergone breast-conserving surgery were eligible for the HF-WBI study . HF-WBI was administered at 43.2 Gy in 16 fractions over 3.2 weeks to the whole breast with an additional tumor-bed boost of 8.1 Gy in 3 fractions over 3 days for positive surgical margins or those < 5 mm . CF-WBI was administered at 50 Gy in 25 fractions over 5 weeks to the whole breast with an additional tumor-bed boost of 16 Gy in 8 fractions over 1.4 weeks to 6 Gy in 3 fractions over 3 days , depending on margin status . Results From April 1 , 2006 , to December 31 , 2010 , 717 patients were registered and 734 breasts were treated by HF-WBI . In the same period , 381 patients and 393 breasts who matched the study criteria chose CF-WBI , so the total number of patients in this comparison was 1,098 . Grade 2 acute skin reactions were observed for 24 patients ( 3 % ) in the HF-WBI group and 53 patients ( 14 % ) in the CF-WBI ( p < 0.001 ) group . The median follow-up period was 27 months . Two cases of intrabreast tumor recurrence were observed in each treatment group . Regional lymph node recurrence was observed in 1 HF-WBI patient and 2 CF-WBI patients . Conclusion HF-WBI is superior to CF-WBI in terms of acute skin reaction and has the same short-term efficacy Background and purpose Adjuvant lymphatic radiotherapy ( LNRT ) is recommended for selected axillary node positive women with early breast cancer . We investigated whether hypofractionated LNRT is safe combined with similarly-hypofractionated breast/chest wall radiotherapy ( RT ) . Material and methods The St and ardisation of Breast Radiotherapy ( START ) pilot , A and B trials r and omised women with early breast cancer to schedules of 2.67–3.3 Gy versus 2.0 Gy fractions ( control ) . RT adverse effects were assessed by patients using the EORTC QLQ-BR23 and protocol -specific questions , and by physicians . Rates of arm/shoulder effects were compared between schedules for patients given LNRT . Results 864/5861 ( 14.7 % ) patients received LNRT ( 385 START-pilot , 318 START-A , 161 START-B ) . Prevalences of moderate/marked arm/shoulder effects were low up to 10 years . There were no significant differences between the hypofractionated and control groups for patient- and physician-assessed symptoms in START-A or START-B. In START-pilot , adverse effect rates were higher after 13 fractions of 3.3 Gy , consistent with effects reported in the breast/chest wall ( significant for shoulder stiffness , HR 3.07 , 95%CI 1.62–5.83 , p = 0.001 ) . Conclusions The START trial results suggest that appropriately-dosed hypofractionated LNRT is safe in the long-term , according to patient and physician-assessed arm and shoulder symptoms . These findings are consistent with those reported after the same schedules delivered to the breast/chest wall Objective : The aim of this study was to compare toxicity and locoregional control of short duration hypofractionated ( HF ) radiotherapy ( RT ) with conventional RT in breast cancer patients . Methods : A total of 100 postmastectomy breast cancer patients were r and omized for adjuvant RT in control group ( comprising fifty patients who received the st and ard conventional dose of 50 Gy in 25 fractions with 2 Gy per fraction ) and study group ( comprising fifty patients who received HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction ) . All patients were treated on linear accelerator with 3-dimensional conformal RT technique . Outcome was analyzed in terms of toxicity , tolerability , and locoregional control . Results : In the present study , at a median follow-up of 20 months , almost similar results were seen in both the groups in terms of toxicity , tolerability , and locoregional control . Adjuvant postmastectomy HF RT was found to be well tolerated with mild-to-moderate side effects that neither reached statistical significance nor warranted any treatment interruption/hospitalization . Conclusions : HF postmastectomy RT is comparable to conventional RT without evidence of higher adverse effects or inferior locoregional tumor control and has an added advantage of increased compliance because of short duration ; hence , it can help in accommodating more breast cancer patients in a calendar year , ultimately result ing in decreased waiting list , increased turnover , and reduced cost of treatment BACKGROUND Breast irradiation after lumpectomy is an integral component of breast-conserving therapy that reduces the local recurrence of breast cancer . Because an optimal fractionation schedule ( radiation dose given in a specified number of fractions or treatment sessions over a defined time ) for breast irradiation has not been uniformly accepted , we examined whether a 22-day fractionation schedule was as effective as the more traditional 35-day schedule in reducing recurrence . METHODS Women with invasive breast cancer who were treated by lumpectomy and had pathologically clear resection margins and negative axillary lymph nodes were r and omly assigned to receive whole breast irradiation of 42.5 Gy in 16 fractions over 22 days ( short arm ) or whole breast irradiation of 50 Gy in 25 fractions over 35 days ( long arm ) . The primary outcome was local recurrence of invasive breast cancer in the treated breast . Secondary outcomes included cosmetic outcome , assessed with the European Organisation for Research and Treatment of Cancer ( EORTC ) Cosmetic Rating System . All statistical tests were two-sided . RESULTS From April 1993 through September 1996 , 1234 women were r and omly assigned to treatment , 622 to the short arm and 612 to the long arm . Median follow-up was 69 months . Five-year local recurrence-free survival was 97.2 % in the short arm and 96.8 % in the long arm ( absolute difference = 0.4 % , 95 % confidence interval [ CI ] = -1.5 % to 2.4 % ) . No difference in disease-free or overall survival rates was detected between study arms . The percentage of patients with an excellent or good global cosmetic outcome at 3 years was 76.8 % in the short arm and 77.0 % in the long arm ; the corresponding data at 5 years were 76.8 % and 77.4 % , respectively ( absolute difference = -0.6 % , 95 % CI = -6.5 % to 5.5 % ) . CONCLUSION The more convenient 22-day fractionation schedule appears to be an acceptable alternative to the 35-day schedule PURPOSE To evaluate the effect of hypofractionated radiation therapy ( HFRT ) of the breast/chest wall and regional nodes on overall survival ( OS ) , disease-free survival ( DFS ) , locoregional control and on treatment-related toxicity in patients with breast cancer and nodal involvement . METHODS AND MATERIAL S Two hundred fifty-seven patients treated between October 2009 and June 2011 with hypofractionated locoregional radiation therapy ( 42 Gy in 15 fractions ) were retrospectively review ed , 51 ( 19.8 % ) after breast-conserving surgery and 206 ( 80.2 % ) after radical surgery . Patients treated with breast-conserving surgery received a boost dose to the tumor bed ( delivered by photons , electrons , or interstitial high-dose-rate brachytherapy ) . Two hundred fifty-six ( 99.6 % ) patients underwent chemotherapy , 209 ( 81.3 % ) had hormonal treatment , and 65 ( 25.3 % ) had anti-HER2 targeted therapy . RESULTS The median follow-up time was 64 months ( range , 11 - 88 months ) . The rates of 5-year OS , DFS , locoregional recurrence (LRR)-free survival , and distant metastasis (DM)-free survival were 86.6 % , 84.4 % , 93.9 % , and 83.1 % , respectively . In multivariate analysis ( MVA ) , lymph node ratio > 65 % , lymphovascular invasion , and negative hormone receptor status predicted for OS , DSF , and DM . T3 to 4 stage was also associated with worse DFS and DM . Finally , for LRR the independent prognostic factors on MVA were N2 to 3 stage and grade 3 . Hyperpigmentation was observed in 19.2 % of patients , telangiectasia in 12.3 % , and fibrosis in 30.7 % . Grade ≥2 lymphedema was recorded in 5.8 % of cases . During the study follow-up , no cardiac or symptomatic pneumonitis was observed , nor were plexopathy or rib fractures . CONCLUSION According to the findings from this retrospective study , HFRT seems to be an acceptable alternative for patients with breast cancer who need regional nodal irradiation . However , prospect i ve r and omized trials are necessary to confirm these preliminary results BACKGROUND Few trials of adjuvant breast radiotherapy have incorporated patient-reported breast symptoms and related areas of quality of life . We assessed these measures in a quality -of-life study that was part of the r and omised START ( St and ardisation of Breast Radiotherapy ) trials . METHODS In START trial A , 2236 patients were r and omly assigned to receive either 39 Gy or 41.6 Gy delivered in 13 fractions over 5 weeks or a global st and ard of 50 Gy in 25 fractions . In START trial B , 2215 women were r and omly assigned to receive either 40 Gy in 15 fractions over 3 weeks or the same control regimen ( 50 Gy in 25 fractions ) as in trial A. 2739 patients were eligible for the quality -of-life study of whom 2208 ( 81 % ) were accrued ( 1129 patients from trial A and 1079 from trial B ) . Participants completed the EORTC QLQ-C30 and BR23 question naires and protocol -specific radiotherapy items up to 5 years after radiotherapy . We compared results across regimens with generalised estimating equations and survival analyses . The START trials are registered , IS RCT N59368779 . FINDINGS At 5 years , up to 40 % women reported moderate or marked changes to the breast after radiotherapy , and arm and shoulder pain affected up to a third of patients . Breast symptoms and body image concerns reduced over time . Rates of radiotherapy adverse effects were lower for the 39 Gy regimen in trial A and the 40 Gy regimen in trial B , compared with the 50 Gy control regimen ; rates of radiotherapy adverse effects were similar between the 41.6 Gy and 50 Gy regimens in trial A. Adverse change in skin appearance was significantly lower for patients who received 39 Gy compared with those who received 50 Gy ( HR 0.63 , 95 % CI 0.47 - 0.84 ) and for those who received 40 Gy compared with those who received 50 Gy ( 0.76 , 0.60 - 0.97 ) ; no significant difference was observed between patients who received 41.6 Gy and those who received 50 Gy in trial A ( 0.83 , 0.63 - 1.08 ) . Patient self-ratings of breast symptoms discriminated a 10 % difference in r and omised dose intensity . Up to a third of women reported moderate or marked pain in the arm and shoulder over 5 years whilst more than 10 % experienced moderate or marked arm and h and swelling , with no significant difference in arm/shoulder subscale scores between the regimens in trial A or trial B ; many baseline arm and shoulder symptoms were associated with prior surgery . INTERPRETATION A substantial proportion of women report moderate or marked breast , arm , and shoulder symptoms over 5 years of follow-up after radiotherapy , but with no detriment to body image . Nonetheless , most patients st and to gain from hypofractionated radiotherapy regimens with a potential for fewer adverse effects ; this strengthens the evidence from the START trials for hypofractionated regimens for women requiring radiotherapy for early breast cancer . FUNDING Cancer Research UK , UK Medical Research Council , UK Department of Health To compare three fractionation schedules in post-mastectomy patients treated with radiotherapy as regard acute and early late effects as well as local recurrence rates . One hundred and seven breast cancer patients treated with modified radical mastectomy and adjuvant radiotherapy ± adjuvant systemic treatments between November 2001 and July 2004 were enrolled in this study . Patients were categorized into three groups . Group A ( 41 patients ) received conventional fractionation 50 Gy over 25 fractions . Group B ( 36 patients ) received other fractionation regimen 45 Gy over 17 fractions . Group C ( 30 patients ) received 40 Gy over 15 fractions . The median follow-up period was 23 months . There has been no statistical significant difference in local control ( P = 0.88 ) , pain ( P = 0.98 ) , telangectasis ( P = 0.23 ) , fibrosis ( P = 0.13 ) , arm oedema ( P = 0.96 ) or pigmentation ( P = 0.80 ) between the three groups . GII-III Erythema was significantly higher in the two hypofractionation arms compared to the control arm ( P = 0.001 ) . Although acute skin reactions were higher in the hypofractionated arms , there was no significant difference in the local recurrence rates or late radiation effects . A national r and omized multicentre study is recommended to explore this further BACKGROUND St and ard curative schedules of radiotherapy to the breast deliver 25 fractions of 2.0 Gy over 5 weeks . In a r and omised trial , we tested whether fewer , larger fractions were at least as safe and as effective as st and ard regimens . In this analysis , we assessed the long-term results of tumour control in the same population . METHODS In 1986 - 98 , we r and omly assigned 1410 women with invasive breast cancer ( tumour stage 1 - 3 with a maximum of one positive node and no metastasis ) who had had local tumour excision of early stage breast cancer to receive 50 Gy radiotherapy given in 25 fractions , 39 Gy given in 13 fractions , or 42.9 Gy given in 13 fractions , all given over 5 weeks . The primary endpoint was late change in breast appearance , which has been reported elsewhere . Here , we report ipsilateral tumour relapse , one of the secondary endpoints . Relapse was defined as any appearance of cancer in the irradiated breast . Analysis was by intention to treat . FINDINGS After a median follow-up of 9.7 years ( IQR 7.8 - 11.8 ) for the 838 ( 95 % ) patients who survived , the risk of ipsilateral tumour relapse after 10 years was 12.1 % ( 95 % CI 8.8 - 15.5 ) in the 50 Gy group , 14.8 % ( 11.2 - 18.3 ) in the 39 Gy group , and 9.6 % ( 6.7 - 12.6 ) in the 42.9 Gy group ( difference between 39 Gy and 42.9 Gy groups , chi2 test , p=0.027 ) . The sensitivity of breast cancer to dose per fraction was estimated to be 4.0 Gy ( 95 % CI 1.0 - 7.8 ) , similar to that estimated for the late adverse effects in healthy tissue from breast radiotherapy . INTERPRETATION Breast cancer tissue is probably just as sensitive to fraction size as dose-limiting healthy tissues . If this finding is confirmed , radiotherapy schedules can be greatly simplified by the delivery of fewer , larger fractions without compromising effectiveness or safety , and possibly improving both INTRODUCTION Although hypofractionated radiotherapy ( HFRT ) has become an accepted option for whole-breast irradiation after breast-conserving surgery , there is limited evidence to support HFRT to the chest wall following mastectomy . We retrospectively analysed post-mastectomy patients treated with HFRT in Christchurch to determine whether HFRT yields acceptable efficacy and toxicity . METHODS The Christchurch oncology data base was used to identify breast cancer patients treated with adjuvant HFRT to the chest wall following a mastectomy between 2003 and 2008 . Eligible post-mastectomy patients were treated with 40 Gy in 16 daily fractions . Treatment outcomes assessed included local recurrence-free survival , breast cancer survival , overall survival and acute toxicities . RESULTS One hundred thirty-three patients were identified . The median follow-up period was 5.03 years . Three patients had a local recurrence as a first event , result ing in 5-year local recurrence-free survival of 97.6 % . Five-year overall survival and 5-year breast cancer survival were 74.7 % and 77.7 % , respectively . The prospect ively assessed acute toxicities were mostly grade 1 . In particular , the incidence of grade 2 skin toxicity was 10.7 % , and no patients experienced grade 3 skin toxicity . CONCLUSION The high local control rate with HFRT , combined with acceptable toxicity and the practical benefits of a shorter treatment time , supports its ongoing use in the eligible patient group . A r and omised controlled trial would be necessary to more completely assess the acute and long-term toxicity of HFRT compared with st and ard fractionation Summary Background The international st and ard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses ( fractions ) . However , a lower total dose delivered in fewer , larger fractions ( hypofractionation ) is hypothesised to be at least as safe and effective as the st and ard treatment . We tested two dose levels of a 13-fraction schedule against the st and ard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size . Methods Between 1998 and 2002 , 2236 women with early breast cancer ( pT1 - 3a pN0 - 1 M0 ) at 17 centres in the UK were r and omly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks . Women were eligible if they were aged over 18 years , did not have an immediate surgical reconstruction , and were available for follow-up . R and omisation method was computer generated and was not blinded . The protocol -specified principal endpoints were local-regional tumour relapse , defined as reappearance of cancer at irradiated sites , late normal tissue effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . Findings 749 women were assigned to the 50 Gy group , 750 to the 41·6 Gy group , and 737 to the 39 Gy group . After a median follow up of 5·1 years ( IQR 4·4–6·0 ) the rate of local-regional tumour relapse at 5 years was 3·6 % ( 95 % CI 2·2–5·1 ) after 50 Gy , 3·5 % ( 95 % CI 2·1–4·3 ) after 41·6 Gy , and 5·2 % ( 95 % CI 3·5–6·9 ) after 39 Gy . The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2 % ( 95 % CI −1·3 % to 2·6 % ) after 41·6 Gy and 0·9 % ( 95 % CI −0·8 % to 3·7 % ) after 39 Gy . Photographic and patient self- assessment s suggested lower rates of late adverse effects after 39 Gy than with 50 Gy , with an HR for late change in breast appearance ( photographic ) of 0·69 ( 95 % CI 0·52–0·91 , p=0·01 ) . From a planned meta- analysis with the pilot trial , the adjusted estimates of α/β value for tumour control was 4·6 Gy ( 95 % CI 1·1–8·1 ) and for late change in breast appearance ( photographic ) was 3·4 Gy ( 95 % CI 2·3–4·5 ) . Interpretation The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size . 41·6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects , a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international st and ard fractionation schedule of 50 Gy in 25 fractions BACKGROUND AND PURPOSE Unlike squamous carcinomas , breast adenocarcinoma may be as sensitive to fraction size as late dose-limiting normal tissues . If so , fewer larger fractions would be as safe and effective as regimens based on 2.0 Gy fractions . The first step is to test the effects of radiotherapy fractions > 2.0 Gy on late normal tissue responses in the breast after tumour excision and radiotherapy for early breast cancer . PATIENTS AND METHODS One thous and four-hundred and ten women with T1 - 3 N0 - 1 M0 invasive breast cancer were r and omised between 1986 - 98 into one of three radiotherapy regimens after local tumour excision of early stage breast cancer ; 50 Gy in 25 fractions ( F ) vs two dose levels of a test schedule giving 39 or 42.9 Gy in 13 F over 5 weeks . Fraction sizes were 2.0 , 3.0 and 3.3 Gy , respectively . The primary endpoint was late change in breast appearance compared to post-surgical appearance scored from annual photographs blinded to treatment allocation . Secondary endpoints included palpable breast in duration ( fibrosis ) and ipsilateral tumour recurrence . RESULTS After a minimum 5-year follow up , the risk of scoring any change in breast appearance after 50 Gy/25 F , 39 Gy/13 F and 42.9 Gy/13 F was 39.6 , 30.3 and 45.7 % , from which an alpha/beta value of 3.6 Gy ( 95 % CI 1.8 - 5.4 ) is estimated . The alpha/beta value for palpable breast in duration was 3.1 Gy ( 95 % CI 1.8 - 4.4 ) . CONCLUSIONS An alpha/beta value of around 3 Gy for late normal tissue changes in the breast is derived from the estimated equivalence of 41.6 Gy in 13 fractions and 50 Gy in 25 fractions over 5 weeks , in line with trial predictions BACKGROUND To our knowledge , no r and omised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer . This study aim ed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy . METHODS This r and omised , non-inferiority , open-label , phase 3 study was done in a single academic hospital in China . Patients aged 18 - 75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3 - 4 disease were eligible to participate . Patients were r and omly assigned ( 1:1 ) according to a computer-generated central r and omisation schedule , without stratification , to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks ( conventional fractionated radiotherapy ) or 43·5 Gy in 15 fractions over 3 weeks ( hypofractionated radiotherapy ) . The modified intention-to-treat population ( including all eligible patients who underwent r and omisation but excluding those who were considered ineligible or withdrew consent after r and omisation ) was used in primary and safety analyses . The primary endpoint was 5-year locoregional recurrence , and a 5 % margin was used to establish non-inferiority ( equivalent to a hazard ratio < 1·883 ) . This trial is registered at Clinical Trials.gov , number NCT00793962 . FINDINGS Between June 12 , 2008 , and June 16 , 2016 , 820 patients were enrolled and r and omly assigned to the conventional fractionated radiotherapy group ( n=414 ) or hypofractionated radiotherapy group ( n=406 ) . 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses . At a median follow-up of 58·5 months ( IQR 39·2 - 81·8 ) , 60 ( 7 % ) patients had developed locoregional recurrence ( 31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group ) ; the 5-year cumulative incidence of locoregional recurrence was 8·3 % ( 90 % CI 5·8 - 10·7 ) in the hypofractionated radiotherapy group and 8·1 % ( 90 % CI 5·4 - 10·6 ) in the conventional fractionated radiotherapy group ( absolute difference 0·2 % , 90 % CI -3·0 to 2·6 ; hazard ratio 1·10 , 90 % CI 0·72 to 1·69 ; p<0·0001 for non-inferiority ) . There were no significant differences between the groups in acute and late toxicities , except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group ( 14 [ 3 % ] of 401 patients vs 32 [ 8 % ] of 409 patients ; p<0·0001 ) . INTERPRETATION Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer . Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients . FUNDING National Key Projects of Research and Development of China ; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences ; and Beijing Marathon of Hope , Cancer Foundation of China |
502 | 11,559,651 | In articles that compared EUS directly with incremental computed tomography , EUS performed better .
EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas .
The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups | BACKGROUND Endoscopic ultrasound ( EUS ) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ .
AIMS To identify and synthesis e findings from all articles on the performance of EUS in tumour , node , metastasis ( TNM ) staging of gastro-oesophageal carcinoma . | BACKGROUND There is a need to assess the sensitivity , specificity , and predictive value of endoscopic ultrasonography ( EUS ) in the diagnosis and staging of gastric cancer and lymphoma . METHODS A prospect i ve study was performed on 86 patients with endoscopic gross appearance suspicious for cancer or lymphoma . Biopsies with endoscopic forceps were always carried out before EUS . All patients underwent laparotomy for final diagnosis , staging , and eventually treatment . The results of EUS were correlated with the histologic findings of the resected specimens , when possible , or with the surgical findings . There were 42 gastric cancers and 44 primary gastric lymphomas . RESULTS EUS made a correct diagnosis of cancer in 35 of 42 patients , with a sensitivity of 83 % . Positive predictability was 87 % , specificity was 97 % , and negative predictability was 96 % . Diagnostic accuracy was 95 % . In the evaluation of cancer depth invasion , EUS was correct in 91 % of cases . EUS displayed perigastric metastatic lymph nodes in 14 of 25 patients , with a sensitivity of 56 % . Positive predictive value was 93 % , specificity was 93 % , and negative predictive value was 54 % . Diagnostic accuracy was 69 % . EUS made a correct diagnosis of lymphoma in 39 of 44 patients , with a sensitivity of 89 % . Positive predictability was 87 % , specificity was 97 % , and negative predictability was 97 % . Diagnostic accuracy was 95 % . In the evaluation of lymphoma depth invasion , EUS was correct in 92 % of cases . EUS displayed metastatic perigastric lymph nodes in 8 of 18 patients , with a sensitivity of 44 % . Positive predictability was 100 % , specificity was 100 % , and negative predictability was 72 % . Diagnostic accuracy was 77 % . CONCLUSIONS From these data it appears that in these diseases EUS has demonstrated specific ultrasonographic features that allow correct diagnosis and staging in the majority of patients . In difficult cases EUS may help to achieve the correct diagnosis . EUS also appear to be a useful tool for staging of gastric cancer and lymphoma . It shows not only tumor depth and local spread but also the passage from a pathologic to a normal wall and lymph node metastasis . With this accurate noninvasive staging procedure , in the near future many patients will no longer undergo exploratory laparotomy for surgical staging . Thanks to EUS , the choice of conservative or surgical treatment can be strongly affected . In case of surgery , EUS can orient the kind of surgical approach . Moreover , the use of EUS for evaluation of therapy during follow-up will probably become of major importance Prospect ively , 72 patients with a gastric carcinoma were studied endosonographically before surgery . The results were correlated with those obtained with the histology of resected specimens according to the new ( 1987 ) TNM classification . Endoscopic ultrasonography ( EUS ) was accurate in assessing the extent and depth of tumor infiltration . Early gastric carcinoma could readily be distinguished from advanced carcinoma . The overall accuracy of EUS was 84.7 % . Occasionally , overstaging and understaging occurred . Stenosis was a factor limiting accurate staging . EUS was reasonably accurate in the assessment of lymph node metastasis . The overall accuracy was 81.0 % . In non-metastatic lymph nodes , however , the accuracy was only 50 % . Difficulties occurred in distinguishing granulomatous lymph nodes and small micrometastatic lymph node involvement . EUS was not accurate in diagnosing distant metastasis , due to the limited depth of penetration of ultrasound . Technical improvements such as a reduction in the diameter of the echoprobe , and the use of the biopsy channel for EUS-guided cytological puncture will further enhance the accuracy of EUS Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis . Resection , the only curative treatment , is confined to early tumour stages . Tumours with local infiltration are usually unresectable and require palliative treatment . Computed tomography has been widely used for preoperative staging but often fails to define this correctly . Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours . In a comparative prospect i ve study , 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement . Thirty seven of these patients underwent operation , resection , or dissection and entered the study . The intraoperative findings or the histopathological assessment , or both , were taken as a reference . For all TN stages of oesophageal tumours , correct preoperative staging was accomplished by endoscopic ultrasound in 89 % for T stage and 69 % for N stage compared with 51 % and 51 % respectively by computed tomography ( highly significant using Fisher 's exact test ) . This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus The dem and for evidence -based healthcare is increasing nationally and internationally and it is equally necessary in both diagnostic and therapeutic practice . Evidence may be collected and combined by means of a systematic literature review of published and unpublished data on a well-defined topic . The output of such review s is then available to guide health policy , influence good practice or direct research . Published guidelines are available on the performance of systematic review s , especially those of r and omized controlled trials . Although there is an extensive literature base of research data in diagnostic imaging there are few such trials , but it is still possible to perform systematic review s. With the alternative study design s encountered it is important to be aware of the main threats to study validity . In this paper the biases likely to be encountered in studies of diagnostic performance are review ed , with particular reference to diagnostic imaging tests . The biases are sub-divided into three categories . The first category is patient selection and covers the validity of generalizing results beyond the study population . The other two , concerning study design and execution and the interpretation of results , affect the likely validity of the results of a study . An underst and ing of these factors is an essential prerequisite for those undertaking or using a systematic literature review in the field of diagnostic imaging . The definitions form the foundations of a defensible review protocol From 1986 to 1990 a prospect i ve comparative study was undertaken to compare the relative accuracy of computed tomography , endogastric ultrasonography , and intraoperative surgical assessment in evaluating the depth of invasion ( T category ) and involvement of lymph nodes ( N category ) of patients with gastric carcinoma . One hundred and eight consecutive patients , who were treated by total gastrectomy and previously evaluated with computed tomography , endogastric ultrasonography , and intraoperative surgical assessment , entered the study . Results ( T and N category ) were compared with those of histopathological staging ( pT and pN category ) . T categories were correctly staged in 43 % of cases with computed tomography , 86 % with endogastric ultrasonography , and 56 % with intraoperative surgical assessment . Computed tomography scanning correctly staged 51 % of all N1 and N2 lymph nodes compared with 74 % for endogastric ultrasonography and 54 % for intraoperative surgical assessment . In general , computed tomography was more accurate for advanced stages of cancer and showed a tendency to overstage the T category and understage N category of gastric tumours . By contrast , endogastric ultrasonography was equally accurate for all T categories and showed an understaging for N categories . Intraoperative surgical assessment overstaged early T stages , understaged T4 tumours , and was equally accurate for all grade s of N categories . Computed tomography scanning and intraoperative surgical assessment of T and N categories were of little value in staging of gastric carcinoma . Endogastric ultrasonography is more accurate than computed tomography scanning and intraoperative surgical assessment . Therefore endogastric ultrasonography should be introduced in the preoperative assessment of patients with gastric carcinoma BACKGROUND Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma . We conducted a prospect i ve , r and omized trial comparing surgery alone with combined chemotherapy , radiotherapy , and surgery . METHODS Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 ( fluorouracil , 15 mg per kilogram of body weight daily for five days , and cisplatin , 75 mg per square meter of body-surface area on day 7 ) and a course of radiotherapy ( 40 Gy , administered in 15 fractions over a three-week period , beginning concurrently with the first course of chemotherapy ) , followed by surgery . The patients assigned to surgery had no preoperative therapy . RESULTS Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery , 10 and 1 , respectively , were withdrawn for protocol violations . At the time of surgery , 23 of 55 patients ( 42 percent ) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases , as compared with 45 of the 55 patients ( 82 percent ) who underwent surgery alone ( P<0.001 ) . Thirteen of the 52 patients ( 25 percent ) who underwent surgery after multimodal therapy had complete responses as determined pathologically . The median survival of patients assigned to multimodal therapy was 16 months , as compared with 11 months for those assigned to surgery alone ( P=0.01 ) . At one , two , and three years , 52 , 37 , and 32 percent , respectively , of patients assigned to multimodal therapy were alive , as compared with 44 , 26 , and 6 percent of those assigned to surgery , with the survival advantage favoring multimodal therapy reaching significance at three years ( P=0.01 ) . CONCLUSIONS Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus The T stage is an important criterion for determining prognosis in esophageal carcinoma . Endosonography , although established as a highly accurate method in preoperative determination of the T stage , may be less reliable in non-traversable tumor stenoses . In a comparative prospect i ve study , 41 patients with carcinoma of the esophagus were investigated to determine the role of tumor stenosis on the accuracy of endosonography in preoperative T staging . The results were correlated with the histology of the resected specimen . The overall accuracy in T staging with endosonography was 76 % , compared with 49 % in computed tomography . T staging results of endosonography were good in easily and non-traversable stenoses ( 92 % , 87 % respectively ) , but lower accuracy was obtained in stenoses which could be traversed only with difficulty ( 46 % ) . Computed tomography was inferior to endosonography in all three groups of patients . The high accuracy of endosonography in non-traversable stenoses might be due to the fact that all tumors were in an advanced stage ( T3 or T4 ) . When passage of the echoendoscope proves difficult , the low focal distance between the ultrasonic transducer and tumor may hamper clear visualisation of the wall layers and tumor penetration depth . These limitations of endosonography should stimulate further efforts in improving ultrasonic resolution in these cases BACKGROUND AND STUDY AIMS Endosonographic staging of esophageal carcinoma may be limited by non-traversable tumor stenoses . Dilation of malignant esophageal strictures carries a significant risk of esophageal perforation . We therefore evaluated the use of ultrasonic miniprobes in the staging of stenotic esophageal carcinoma compared with conventional endoscopic ultrasound . PATIENTS AND METHODS In a blinded , prospect i ve study , which included histopathological evaluation , 53 consecutive patients ( 43 male , 10 female , mean age 61 years ) with stenosing esophageal carcinomas were examined preoperatively . Endosonography was done using the optical GF-UM3 echo endoscope . If tumor strictures were not traversable with this instrument , a blind esophagoprobe , the MH-908 was used for endosonography . Miniprobe sonography ( MPS ) was done during esophagoscopy in all patients . The various imaging modalities were assessed in terms of complete tumor traversability and correct tumor staging . Every patient underwent surgical tumor resection . RESULTS MPS of the esophagus and proximal parts of the stomach was possible in all 53 patients without prior dilation of tumor stenoses . Endosonography with the GF-UM3 instrument was precluded in 23 patients ( 43.4 % ) while in 20 of the latter patients the MH 908 esophagoprobe could be passed through tumor stenoses . The overall accuracy rates for depth of tumor infiltration ( T ) staging were : 62 % ( 31/50 ) for endosonography ( GF-UM3 plus esophagoprobe ) and 86.8 % ( 46/53 ) for MPS . The accuracy rates for T staging in tumors traversable both with the GF-UM3 echo endoscope and with miniprobes were 56.7 % ( 17/30 ) for GF-UM3 and 80 % ( 24/30 ) for MPS . The accuracy rates for T staging in tumors traversable only with the MH-908 esophagoprobe and with miniprobes were 70 % ( 14/20 ) for the MH-908 and 95 % ( 19/20 ) for MPS . With regard to the presence or absence of peri-esophageal metastatic lymph nodes ( N staging ) , the accuracy rates were 83 % ( 25/30 ) for MPS and 70 % ( 21/30 ) for the GF-UM3 , and 80 % ( 16/20 ) for MPS and 70 % ( 14/20 ) for the MH-908 . CONCLUSION Compared with conventional endosonography using 7.5-MHz large diameter instruments , MPS enables : a ) safe passage through high- grade malignant esophageal strictures , achieving b ) higher accuracy rates for T staging , and c ) similar rates for N staging . The use of MPS can also represent an improvement in the comfort and safety of patients . Moreover , miniprobe sonography is highly cost-effective compared with conventional endosonography . Thus , MPS appears to be a valuable addition to the armamentarium for staging esophageal carcinoma Abstract . Background : To evaluate the diagnostic accuracy of endosonography ( ES ) in a prospect i ve series of cancer of the cardia . Methods : Thirty-five patients with cancer of the cardia were investigated by ES ; 29 underwent surgery . ES staging for the surgery patients was compared with histopathologic findings . Tumors were staged according to the 1987 TNM classification . Results : ES had a diagnostic accuracy of 79 % for the T category , 79 % for the N category , 89 % for the M category , and 72 % for prognostic TNM staging . Conclusion : ES is an excellent para clinical modality for the staging of local – regional spread of cancer of the cardia and a useful complement to computed tomography for evaluation of these tumors To assess the accuracy and limitations of endoscopic ultrasonography ( EUS ) in the preoperative staging of esophageal and gastric carcinoma , we performed a prospect i ve controlled study over a five year period . Data from 63 patients with esophageal cancer and 147 patients with gastric cancer who underwent surgery were available for comparison of the endosonographic TNM classification to the histophathological findings of the resected specimens . The overall accuracy of EUS in the assessment of tumor infiltration depth was 85.7 % and 78 % in esophageal and gastric cancer , respectively . The sensitivity of EUS in the detection of regional lymph node metastases was 90 % in esophageal and 87 % in gastric carcinoma . The most frequent causes of misdiagnoses by endosonography were microscopic tumor invasion and peritumorous inflammatory changes . The inability to traverse a tumor stenosis restricted the endosonographic evaluation in 31.6 and 14 % of the cases with esophageal and gastric cancer , respectively The aim of the study was to evaluate the usefulness of and problems associated with a new endoscopically guided ultrasound miniprobe , used for pre-operative staging of gastric cancers . 59 cases of gastric cancer were prospect ively examined with a 15 MHz ultrasound miniprobe . The results of the ultrasound imaging were compared with the histological findings of the resected specimens . The accuracy of the miniprobe for depth of invasion ( T category ) was 61 % for all tumours , and 72 % and 40 % , respectively , for T1 and T2 to T4 lesions . If indeterminate cases due to ultrasound attenuation were excluded , the accuracy was improved to 82 % for T1 and 57 % for T2 to T4 tumours , respectively . The accuracy of the miniprobe for nodal staging ( N category ) was 69 % overall , and 86 % , 25 % and 14 % for stages N0 , N1 and N2 , respectively . In tumours classified on the basis of endoscopic types , the miniprobe staged early type gastric cancers ( T category = 73 % , N category = 80 % ) significantly ( p < 0.01 ) more accurately than advanced ones ( T category = 21 % , N category = 36 % ) . This study suggests that the miniprobe is indicated for pre-operative TN staging when endoscopy reveals an early gastric cancer Despite encouraging results from Europe and America , endoscopic ultrasound ( EUS ) has yet to become established in the United Kingdom . The aims of this prospect i ve study were to investigate its value in the assessment of patients with benign and malignant oesophageal conditions , and in particular to assess its reliability for local tumour ( T ) and lymph node ( N ) staging in patients with oesophageal cancer . EUS was performed in 90 patients : 23 were normal controls , 17 had benign oesophageal diseases and 50 had operable oesophageal cancer . Detailed measurements of the oesophageal wall and regional nodes were made and the accuracy of EUS for locoregional tumour staging was compared with final histology . EUS visualised the normal oesophageal wall as a multilayered structure , thicker distally than proximally . Distal stenotic conditions caused thickening of the proximal wall and loss of this gradient . EUS was highly accurate for both local tumour ( 92 % correct ) and lymph node staging ( 86 % correct ) and was better than computed tomography , magnetic resonance imaging and open staging performed by the surgeon . Fine needle aspiration biopsy using radial scanning EUS guidance was shown to be feasible . EUS is a valuable technique for investigation of both benign and malignant oesophageal conditions . It provides highly accurate local tumour and regional lymph node staging data in patients with oesophageal cancer BACKGROUND / AIMS To assess the accuracy and limitation of endoscopic ultrasonography in preoperative staging of gastric cancer , we performed a prospect i ve study on 99 patients . MATERIAL AND METHODS Ninety-nine patients with gastric cancer had preoperative staging with endoscopic ultrasound ( EUS ) and CT . RESULTS The depth of infiltration ( T parameter ) was correctly defined by EUS in 58/65 patients ( 89 % ) . The lymph node involvement ( N parameter ) was correctly classified in 44/65 patients ( 68 % ) , the sensitivity was 74 % and the specificity was 54 % . The most frequent cause of understaging T parameter was microscopic tumor invasion , whereas overstaging was due to peri-tumor inflammation . CONCLUSIONS We believe that EUS is a reliable method , superior to all diagnostic tools , in the evaluation of locoregional extension of gastric cancer Endoscopic ultrasonography is technically limited in patients with obstructing oesophageal cancers if the endoscope can not pass beyond the lesion . This problem may be overcome by preliminary endoscopic tumour dilatation , or by the use of narrower calibre ‘ blind ’ endoscopic ultrasonographic telescopes or fine‐bore endoscopic ultrasonographic miniprobes . These alternatives are either potentially hazardous or time consuming and expensive . The aim of this prospect i ve study was to determine the effect of oesophageal obstruction on the locoregional staging accuracy of endoscopic ultrasonography for oesophageal cancer |
503 | 28,008,728 | Substantial consensus was also reached on the benefit of multidisciplinary team discussion and the achievability of a ( near ) complete cytoreduction ( CC0 - 1 ) without supporting evidence . | AIM This systematic review aim ed to provide an overview of (inter)national guidelines on the treatment of peritoneal metastases of colorectal cancer origin ( PMCRC ) and to determine the degree of consensus and available evidence with identification of topics for future research . | Background Cytoreductive surgery (CRS)/Hyperthermic Intraperitoneal Chemotherapy ( HIPEC ) is associated with prolonged survival in selected patients with peritoneal surface disease . Yet , for elderly patients ( older than 70 years of age ) CRS/HIPEC is controversial , due to associated morbidity . Methods A retrospective analysis of a prospect i ve data base of 950 procedures was performed . Type of malignancy , demographics , performance and resection status , hospitalization , morbidity , mortality , and survival were review ed . Results A total of 81 patients ( median age 73 , range 70–87 ) underwent CRS/HIPEC between 1991 and 2011 . Median follow-up was 48.1 months . Complete cytoreduction was achieved in 44 % . Median survival was 31.8 months for appendiceal cancer , 41.5 for mesothelioma , 54.0 for ovarian cancer , 13.2 for colon cancer , and 7.6 for gastric cancer . The 30-day mortality was 13.6 % . The combined grade III and IV morbidity was 38 % . Median ICU and hospital stay for uncomplicated patients was 1 and 8 days , respectively . The 3-month mortality was 27.4 % . There were no deaths in the octogenarian group . In stepwise multivariate analysis , type of primary ( p = 0.03 ) , albumin ( p = 0.02 ) , and R status ( p = 0.007 ) were predictive of survival only in the absence of complications . Splitting the data at the midpoint of surgical experience , there was a drop in 1- and 3-month mortality over time to 9.5 and 19.3 % , respectively , while the median survival increased from 11.2 ( N = 39 ) to 46.9 months ( N = 42 ) . Conclusions HIPEC in the elderly is associated with a steep learning curve and considerable morbidity and mortality . However , age alone is not a contraindication for the procedure . Institutional experience and stringent patient selection are key factors for prolonged survival Objective : The aim of this prospect i ve study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis ( PC ) at an early stage in a series of patients at high risk of developing PC from colorectal cancer . Background : The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy ( HIPEC ) after complete cytoreductive surgery ( CCRS ) , and could be further improved if PC could be treated at an early stage . But , currently , the diagnosis of early PC is not accessible to imaging . Patients and Methods : From 1999 to 2006 , 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor . Patients were selected according to primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 16 ) , synchronous ovarian metastases ( n = 4 ) , perforated primary tumor ( n = 9 ) . Results : PC was found and treated with CCRS plus HIPEC in 16 of 29 ( 55 % ) cases , corresponding to 10 of 16 patients with initial PC , 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor . There was no postoperative mortality , and morbidity ( grade III/IV ) occurred in 14 % of cases . After a median follow-up of 27 months ( range , 6–96 ) , 8 of 16 patients treated with CCRS and HIPEC are free of disease , 4 relapsed in the peritoneum , and 4 developed isolated visceral metastases . Conclusion : Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55 % of cases . Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospect i ve multicenter trial Introduction The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy . In 2003 , a r and omized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy . This trial showed a positive result favoring the studied treatment . This trial has now been up date d to a minimal follow-up of 6 years to show long-term results . Patients and Methods For all patients still alive , the follow-up was up date d until 2007 . In the original study , four patients were excluded — two because of no eligible histology/pathology and two because of major protocol violations . After r and omization , four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy , one patient because of withdrawal , one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment . During the follow-up , one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease , after the assigned treatment was completed . The data from these patients were censored at the moment of the cross-over . Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method . The long-term results were studied in more detail to evaluate efficacy and toxicity . Results At the time of this up date , the median follow-up was almost 8 years ( range 72–115 months ) . In the st and ard arm , 4 patients were still alive , 2 with and 2 without disease ; in the “ HIPEC ’ arm , 5 patients were still alive , 2 with and 3 without disease . The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm ( P = 0.020 ) . The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm ( P = 0.028 ) . The 5-year survival was 45 % for those patients in whom a R1 resection was achieved . Conclusion With 90 % of all events having taken place up to this time , this r and omized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin . For a selected group , there is a possibility of long-term survival Background We evaluate the long-term survival of patients with peritoneal carcinomatosis ( PC ) treated with systemic chemotherapy regimens , and the impact of the of the retrospective peritoneal disease severity score ( PSDSS ) on outcomes . Methods One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987 - 2006 were identified from a prospect i ve institutional data base . These patients either received no chemotherapy , 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy . Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinical ly relevant factors . Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test . Results Median survival was 5 months ( 95 % CI , 3 - 7 months ) for patients who had no chemotherapy , 11 months ( 95 % CI , 6 - 9 months ) for patients treated with 5 FU/LV , and 12 months ( 95 % CI , 4 - 20 months ) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy . Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy ( p = 0.026 ) . PSDSS staging was identified as an independent predictor for survival on multivariate analysis [ RR 2.8 ( 95%CI 1.5 - 5.4 ) ; p < 0.001 ] . Conclusion A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy . The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin Purpose This nationwide study evaluated results of cytoreductive surgery ( CRS ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) for peritoneal metastasis of colorectal origin in the Netherl and s following a national protocol . Methods In a multi-institutional study prospect i ve data bases of patients with peritoneal carcinomatosis ( PC ) from colorectal cancer and pseudomyxoma peritonei ( PMP ) treated according to the Dutch HIPEC protocol , a uniform approach for the CRS and HIPEC treatment , were review ed . Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival . Results Nine-hundred sixty patients were included ; 660 patients ( 69 % ) were affected by PC of colorectal carcinoma and the remaining suffered from PMP ( 31 % ) . In 767 procedures ( 80 % ) , macroscopic complete cytoreduction was achieved . Three-hundred and thirty one patients had grade III – V complications ( 34 % ) . Thirty-two patients died perioperatively ( 3 % ) . Median length of hospital stay was 16 days ( range 0–166 days ) . Median follow-up period was 41 months ( 95 % confidence interval ( CI ) , 36–46 months ) . Median progression-free survival was 15 months ( 95 % CI 13–17 months ) for CRC patients and 53 months ( 95 % CI 40–66 months ) for PMP patients . Overall median survival was 33 ( 95 % CI 28–38 months ) months for CRC patients and 130 months ( 95 % CI 98–162 months ) for PMP patients . Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients . Conclusions The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP . It is assumed the uniform Dutch HIPEC protocol was beneficial Background To prospect ively investigate the diagnostic accuracy of a 64-section multi-detector row computed tomography ( CT ) for the detection of peritoneal metastases , with the use of surgery and histopathological findings as the reference st and ard . Methods The study cohort comprised 18 patients with peritoneal carcinomatosis who underwent multiphasic CT with a 64-section CT , 0–119 days before cytoreductive surgery . Transverse CT images along with isotropic reformatted coronal and sagittal images were prospect ively and independently evaluated by one of the five staff radiologists in an unblinded fashion . Results The overall sensitivity , specificity , positive , and negative predictive values of CT for the detection of peritoneal metastases were , respectively , 75 % ( 93 of 124 lesions ; confidence interval [ CI ] 68–84 ) , 92 % ( 118 of 128 ; CI 85–96 ) , 90 % ( 93 of 103 ; CI 83–95 ) , and 79 % ( 118 of 149 ; CI 72–86 ) . For lesions 0.5 cm in diameter or larger , CT yielded a mean sensitivity of 89 % ( 77 of 87 ; CI 75–97 ) , although sensitivity decreased to only 43 % ( 16 of 37 ; CI 28–56 ) for lesions < 0.5 cm in diameter . Conclusions 64-Section CT with the addition of isotropic reformatted coronal and sagittal images is a very effective technique in the detection of peritoneal metastases of 0.5 cm in diameter or larger , although sensitivity decreases remarkably for lesions < 0.5 cm in diameter AIM The present study was specifically design ed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether currently used criteria appropriately select c and i date s for peritonectomy procedures ( cytoreductive surgery ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) . PATIENTS AND METHODS Preoperative , operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospect ively entered in a common data base . Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors . RESULTS Over a minimum 24-month follow-up , the overall morbidity rate was 27.4 % ( mortality rate : 2.7 % ) and was directly related to the extent of surgery . Peritoneal cancer index ( PCI ) , unfavorable peritoneal sites , synchronous or previously resected liver metastasis and the completeness of cytoreduction , all emerged as independent prognostic factors correlated with survival . CONCLUSIONS Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis , patients should be selected according to the existing independent prognostic variables PURPOSE Symptoms and complications of metastatic colorectal cancer ( mCRC ) differ by metastatic sites . There is a paucity of prospect i ve survival data for patients with peritoneal carcinomatosis colorectal cancer ( pcCRC ) . We characterized outcomes of patients with pcCRC enrolled onto two prospect i ve r and omized trials of chemotherapy and contrasted that with other manifestations of mCRC ( non-pcCRC ) . METHODS A total of 2,095 patients enrolled onto two prospect i ve r and omized trials were evaluated for overall survival ( OS ) and progression-free survival ( PFS ) . A Cox proportional hazard model was used to assess the adjusted associations . RESULTS The characteristics of the pcCRC group ( n = 364 ) were similar to those of the non-pcCRC patients in median age ( 63 v 61 years , P = .23 ) , sex ( 57 % males v 61 % , P = .23 ) , and performance status ( Eastern Cooperative Oncology Group performance status 0 or 1 94 % v 96 % , P = .06 ) , but differed in frequency of liver ( 63 % v 82 % , P < .001 ) and lung metastases ( 27 % v 34 % , P = .01 ) . Median OS ( 12.7 v 17.6 months , hazard ratio [ HR ] = 1.3 ; 95 % CI , 1.2 to 1.5 ; P < .001 ) and PFS ( 5.8 v 7.2 months , HR = 1.2 ; 95 % CI , 1.1 to 1.3 ; P = .001 ) were shorter for pcCRC versus non-pcCRC . The unfavorable prognostic influence of pcCRC remained after adjusting for age , PS , liver metastases , and other factors ( OS : HR = 1.3 , P < .001 ; PFS : HR = 1.1 , P = .02 ) . Infusional fluorouracil , leucovorin , and oxaliplatin was superior to irinotecan , leucovorin , and fluorouracil as a first-line treatment among pcCRC ( HR for OS = 0.62 , P = .005 ) and non-pcCRC patients ( HR = 0.66 , P < .001 ) . CONCLUSION pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC . Future trials for mCRC should consider stratifying on the basis of pcCRC status Background Oxaliplatin ( OX ) is increasingly used for hyperthermic intraperitoneal chemotherapy ( HIPC ) for patients with peritoneal metastases . Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin ( OX ) versus mitomycin C ( MMC ) . Material s and Methods We included patients enrolled in single-institution prospect i ve clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX . We review ed patient demographics , pathology , perioperative course , HIPC administration , and postoperative electrolyte disturbances . Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula : ( measured Na+ ) × [ ( glucose − 100/100 ) × 1.6 ] . Results From January 2002 to April 2009 we performed 80 HIPC procedures . A total of 60 patients ( 75 % ) received MMC ( dose range 12.5–50 mg/m2 ) carried in lactated ringers solution . There were 20 patients ( 25 % ) who received OX ( dose range 300 × 400 mg/m2 ) carried in 5 % dextrose solution . For patients receiving HIPC with OX , electrolyte disturbances were the most common complication . Compared with MMC , patients receiving OX had significant 24-h postoperative uncorrected hyponatremia ( P < 0.001 ) , corrected hyponatremia ( P < 0.001 ) , hyperglycemia ( P < 0.001 ) , and metabolic acidosis ( P < 0.001 ) . In the OX group , corrected ( mean 130.5 ) and uncorrected ( mean 127.4 ) sodium levels were significantly lower than preoperatively ( mean 139.9 , P < 0.001 ) . The overall nonelectrolyte complication rate was 56.2 % . ( MMC n = 33 , 55.0 % ; OX n = 12 , 60 % ) ; the 30-day mortality rate was 0 % in both groups . Conclusions Compared with MMC , HIPC with OX was associated with significant but predictable electrolyte disturbances ; however , these electrolyte disturbances were not associated with higher overall complication rates . Close monitoring with early correction is imperative to maximize perioperative care . Further studies are needed to provide mechanistic insight Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer . Cytoreduction followed by hyperthermic intraperitoneal chemotherapy ( HIPEC ) is a new treatment option . Patient selection is crucial to outcome Background : Cytoreductive surgery ( CS ) and intraperitoneal hyperthermic chemotherapy ( IPHC ) are efficacious in patients with disseminated mucinous tumors of the appendix . We review ed our experience using this approach for nonappendiceal colorectal cancer ( NACC ) . Methods : We performed a retrospective chart review of a prospect i ve data base for patients undergoing CS and IPHC with mitomycin C for peritoneal carcinomatosis from colorectal primary lesions between December 1991 and April 2002 . Results : There were 77 patients , with a median age of 54 years . Peritoneal carcinomatosis was synchronous and metachronous in 27 % and 73 % patients , respectively . Seventy-five percent of patients ( n = 58 ) had received chemotherapy prior to IPHC . Complete resection of all gross disease was accomplished in 37 patients ( 48 % ) . The mean carcinoembryonic antigen level decreased from a preoperative value of 31.2 to a postoperative value of 6.9 ( P < .0001 ) . Overall survival ( OS ) at 1 , 3 , and 5 years was 56 % , 25 % , and 17 % , respectively . With a median follow-up of 15 months , the median OS was 16 months . Perioperative morbidity and mortality were 30 % and 12 % , respectively . Hematologic toxicity occurred in 15 patients ( 19 % ) . Cox regression analysis identified poor performance status ( P = .018 ) , bowel obstruction ( P = .001 ) , malignant ascites ( P = .001 ) , and incomplete resection of gross disease ( P = .011 ) as independent predictors of decreased survival . Patients with complete resection of all gross disease had a 5-year OS of 34 % , with a median OS of 28 months . Conclusions : CS and IPHC with mitomycin C can improve outcomes for select patients with peritoneal spread from NACC . One third of patients who undergo complete resection of gross disease have long-term survival PURPOSE To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis ( PC ) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) . PATIENTS AND METHODS All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated . The st and ard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period , but who had not benefited from HIPEC because the technique was unavailable in the center at that time . RESULTS Forty-eight patients were retrospectively included in the st and ard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospect ively . All characteristics were comparable except age and tumor differentiation . There was no difference in systemic chemotherapy , with a mean of 2.3 lines per patient . Median follow-up was 95.7 months in the st and ard group versus 63 months in the HIPEC group . Two-year and 5-year overall survival rates were 81 % and 51 % for the HIPEC group , respectively , and 65 % and 13 % for the st and ard group , respectively . Median survival was 23.9 months in the st and ard group versus 62.7 months in the HIPEC group ( P < .05 , log-rank test ) . CONCLUSION Patients with isolated , resectable PC achieve a median survival of 24 months with modern chemotherapies , but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months , with a 5-year survival rate of 51 % |
504 | 26,733,650 | Overall , all four non-operative modalities of treatment were found to have a significant effect on the reduction of pain in OA of the knee .
This study shows that non-operative physical modalities of treatment are of benefit when treating OA of the knee . | The purpose of this study was to evaluate the effect of various non-operative modalities of treatment ( transcutaneous electrical nerve stimulation ( TENS ) ; neuromuscular electrical stimulation ( NMES ) ; insoles and bracing ) on the pain of osteoarthritis ( OA ) of the knee .
We conducted a systematic review according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses guidelines to identify the therapeutic options which are commonly adopted for the management of osteoarthritis ( OA ) of the knee . | Objective Mechanical factors , in particular increased medial knee joint load , are believed to be important in the structural progression of knee osteoarthritis . This study evaluated the relationship of medial knee load during walking to indices of structural disease progression , measured on MRI , in people with medial knee osteoarthritis . Methods A longitudinal cohort design utilising a subset of participants ( n=144 , 72 % ) enrolled in a r and omised controlled trial of lateral wedge insoles was employed . Medial knee load parameters including the peak knee adduction moment ( KAM ) and the KAM impulse were measured at baseline using three-dimensional gait analysis during walking . MRI at baseline and at 12 months was used to assess structural indices . Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume . Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions ( BML ) . Results A higher KAM impulse , but not peak KAM , at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months ( β=29.9 , 95 % CI 6.3 to 53.5 , p=0.01 ) . No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML . Conclusion This study suggests knee loading , in particular the KAM impulse , may be a risk factor for loss of medial tibial cartilage volume . As knee load is modifiable , load-modifying treatments may potentially slow disease progression Background There is controversial evidence regarding whether foot orthoses or knee braces improve pain and function or correct malalignment in selected patients with osteoarthritis ( OA ) of the medial knee compartment . However , insoles are safe and less costly than knee bracing if they relieve pain or improve function . Questions / purpose sWe therefore asked whether laterally wedged insoles or valgus braces would reduce pain , enhance functional scores , and correct varus malalignment comparable to knee braces . Patients and Methods We prospect ively enrolled 91 patients with symptomatic medial compartmental knee OA and r and omized to treatment with either a 10-mm laterally wedged insole ( index group , n = 45 ) or a valgus brace ( control group , n = 46 ) . All patients were assessed at 6 months . The primary outcome measure was pain severity as measured on a visual analog scale . Secondary outcome measures were knee function score using WOMAC and correction of varus alignment on AP whole-leg radiographs taken with the patient in the st and ing position . Additionally , we compared the percentage of responders according to the OMERACT-OARSI criteria for both groups . Results We observed no differences in pain or WOMAC scores between the two groups . Neither device achieved correction of knee varus malalignment in the frontal plane . According to the OMERACT-OARSI criteria , 17 % of our patients responded to the allocated intervention . Patients in the insole group complied better with their intervention . Although subgroup analysis results should be translated into practice cautiously , we observed a slightly higher percentage of responders for the insole compared with bracing for patients with mild medial OA . Conclusions Our data suggest a laterally wedged insole may be an alternative to valgus bracing for noninvasively treating symptoms of medial knee OA.Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of level of evidence We examined if a subject-specific amount of lateral wedge added to a foot orthosis could alter knee mechanics to potentially reduce the progression of knee osteoarthritis in patients with medial knee osteoarthritis . Twenty individuals with medial knee osteoarthritis ( > /=2 Kellgren Lawrence grade ) were prescribed a custom laterally wedged foot orthotic device . The prescribed wedge amount was the minimal wedge amount that provided the maximum amount of pain reduction during a lateral step-down test . Following an accommodation period , all subjects returned to the laboratory for a gait analysis . Knee mechanics were collected as the subjects walked at an intentional walking speed . Walking in the laterally wedged orthotic device significantly reduced the peak adduction moment during early stance ( p < 0.01 ) compared to the nonwedged device . Similarly , the wedged orthotic device significantly reduced the knee adduction excursion from heel strike to peak adduction ( p < 0.01 ) compared to the nonwedged device . No differences in the peak adduction moment during propulsion or peak adduction during stance were observed between the orthotic conditions . A subject-specific laterally wedged orthotic device was able to reduce the peak knee adduction moment during early stance , which is thought to be associated with the progression of knee osteoarthritis . Previous studies on this device have reported issues associated with foot discomfort when using wedge amounts > 7 degrees ; however , no such issues were reported in this study . Therefore , providing a custom laterally wedged orthotic device may potentially increase compliance while still potentially reducing disease progression OBJECTIVE To compare the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , interferential currents ( IFCs ) , and shortwave diathermy ( SWD ) against each other and sham intervention with exercise training and education as a multimodal package . DESIGN A double-blind , r and omized , controlled , multicenter trial . SETTING Departments of physical medicine and rehabilitation in 4 centers . PARTICIPANTS Patients ( N=203 ) with knee osteoarthritis ( OA ) . INTERVENTIONS The patients were r and omized by the principal center into the following 6 treatment groups : TENS sham , TENS , IFCs sham , IFCs , SWD sham , and SWD . All interventions were applied 5 times a week for 3 weeks . In addition , exercises and an education program were given . The exercises were carried out as part of a home-based training program after 3 weeks ' supervised group exercise . MAIN OUTCOME MEASURES Primary outcome was a visual analog scale ( 0 - 100 mm ) to assess knee pain . Other outcome measures were time to walk a distance of 15 m , range of motion , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Nottingham Health Profile , and paracetamol intake ( in grams ) . RESULTS We found a significant decrease in all assessment parameters ( P<.05 ) , without a significant difference among the groups except WOMAC stiffness score and range of motion . However , the intake of paracetamol was significantly lower in each treatment group when compared with the sham groups at 3 months ( P<.05 ) . Also , the patients in the IFCs group used a lower amount of paracetamol at 6 months ( P<.05 ) in comparison with the IFCs sham group . CONCLUSIONS Although all groups showed significant improvements , we can suggest that the use of physical therapy agents in knee OA provided additional benefits in improving pain because paracetamol intake was significantly higher in the patients who were treated with 3 sham interventions in addition to exercise and education Background : Knee joint osteoarthritis ( OA ) is one of the most incapacitating diseases affecting older population , which is associated with pain and functional limitation . Various kinds of conservative treatment have been used to decrease knee pain and to improve the quality of life of the subjects suffering from this disease . There are discrepancies in the clinical effects reported for the use of lateral wedge insole in spite of being used as one of the first conservative mechanical treatments for patients with medial compartments of knee OA . Methods : A total of 36 subjects with medial knee compartment OA were recruited in this research project . Subjects were r and omized into two groups to receive 3- and 7-mm lateral wedge insoles based on the date of birth of the participants . Some parameters such as severity of knee pain , Tibiofemoral angle ( TFA ) , severity of OA , and quality of life were selected in this research project . Results : The use of both 3-mm and 7-mm lateral wedge insole improves the quality of life and decreases knee joint pain . However , the effect of 7 mm lateral wedge insole was more than that of 3 mm . Conclusion : Using lateral wedge insole is a simple , inexpensive therapy for decreasing pain and improving quality of life ; however , most research must be carried out to find the effects of lateral wedge on severity of knee joint OA and aligning TFA Background The present study tests whether a combined treatment of acupuncture and transcutaneous electrical nerve stimulation ( TENS ) is more effective than acupuncture or TENS alone for treating knee osteoarthritis ( OA ) . Methods Thirty-two patients with knee OA were r and omly allocated to four groups . The acupuncture group ( ACP ) received only acupuncture treatment at selected acupoints for knee pain ; the TENS group ( TENS ) received only TENS treatment at pain areas ; the acupuncture and TENS group ( A&T ) received both acupuncture and TENS treatments ; the control group ( CT ) received topical poultice ( only when necessary ) . Each group received specific weekly treatment five times during the study . Outcome measures were pain intensity in a visual analogue scale ( VAS ) and knee function in terms of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Results The ACP , TENS and A&T groups reported lower VAS and WOMAC scores than the control group . Significant reduction in pain intensity ( P = 0.039 ) and significant improvement in knee function ( P = 0.008 ) were shown in the A&T group . Conclusion Combined acupuncture and TENS treatment was effective in pain relief and knee function improvement for the sample d patients suffering from knee OA Pneumatic unloader bracing with extension assists have been proposed as a non-operative modality that may delay the need for knee surgery by reducing pain and improving function . This prospect i ve , r and omized trial evaluated 52 patients who had knee osteoarthritis for changes in : ( 1 ) muscle strength ; ( 2 ) objective functional improvements ; ( 3 ) ; subjective functional improvements ; ( 4 ) pain ; ( 5 ) quality of life ; and ( 6 ) conversion to total knee arthroplasty ( TKA ) compared to st and ard of care . Patient outcomes were evaluated at a minimum 3 months . Braced patient 's demonstrated significant improvements in muscle strength , several functional tests , and patient reported outcomes when compared to the matched cohort . These results are encouraging and suggest that this device may represent a promising alternative to st and ard treatment methods for knee osteoarthritis The aim of this study was to evaluate the effects of electrical stimulation program on pain , disability , and quadriceps strength in the patients with knee osteoarthritis . Fifty women diagnosed as knee osteoarthritis were r and omized into two groups as electrical stimulation and biofeedback-assisted isometric exercises . Both of the programs were performed 5 days a week , for a duration of 4 weeks . Outcome measures for pain were visual analogue scale pain score and Western Ontario McMaster osteoarthritis index ( WOMAC ) pain score . Disability and stiffness were assessed with WOMAC physical function and stiffness score . One repetition maximum ( RM ) and 10 RM were used for measuring quadriceps strength . In addition , 50 m walking time and 10 steps stairs climbing up-down time were evaluated . Both groups showed significant improvements in pain , physical function , and stiffness scores after the therapy . There were statistically significant improvements in 50 m walking time and 10 steps stairs climbing up-down time and 1 RM and 10 RM values indicating the improvement in muscle strength . In addition , there were no significant differences between the groups after the therapy . We conclude that electrical stimulation treatment was as effective as exercise in knee osteoarthritis and electrical stimulation treatment can be suggested especially for the patients who have difficulty in or contraindications to perform an exercise program This study tested the effectiveness of episodic transcutaneous electrical nerve stimulation ( TENS ) as a supplement to pharmacologic analgesia on pain with movement and at rest after abdominal surgery and evaluated whether its use during walking and vital capacity maneuvers enhances performance of these activities . TENS , with a modulated frequency , intensity as high as the subject could tolerate , and electrodes placed on either side and parallel to the incision , was compared to placebo TENS and pharmacologic analgesia alone ( control ) by using a crossover design . Self-report of pain intensity , walking function , and vital capacity were assessed on 33 subjects . TENS result ed in significantly less pain than the control during both walking ( P < .5 ) and vital capacity activities ( P < .1 ) and significantly less pain than placebo TENS during vital capacity ( P < .01 ) . TENS also produced significantly better gait speeds than the control ( P < .05 ) and greater gait distances ( P < .01 ) than the control and placebo TENS . Vital capacity and pain intensity at rest were not significantly different among the 3 treatments . These results suggest TENS reduces pain intensity during walking and deep breathing and increases walking function postoperatively when used as a supplement to pharmacologic analgesia . The lack of effect on pain at rest supports the hypothesis that TENS works through reducing hyperalgesia The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospect i ve , single-blind , block-r and omized controlled design . Sixty-six subjects ( 29 males , 37 females , mean age 62.4 years , mean BMI 33.0 kg/m(2 ) ) were block-r and omized to a lateral wedge ( treatment ) or neutral ( control ) orthotic group . Both groups were issued a st and ardized walking shoe for use with the orthoses . Primary outcome measures included the pain , stiffness , and functional limitations subscales of the Western Ontario and McMaster Universities index . Secondary outcome measures included the 6-minute walk distance and pain change , and stair negotiation time and pain change . A significant interaction ( p=0.039 ) favoring the treatment group was observed for pain change during the 6-minute walk . The treatment group demonstrated significant improvements at both 1 month ( p<0.001 ) and 1 year ( p<0.001 ) compared to baseline . The control group only demonstrated significant improvements at 1 year ( p=0.017 ) . No other interactions were observed . Both groups were improved at each follow-up in the WOMAC subscales for pain ( p<0.001 ) , stiffness ( p<0.001 ) , and physical function ( p<0.001 ) . Both groups also improved in 6-minute walk test distance ( p<0.001 ) , stair negotiation test time ( p=0.004 ) , and stair negotiation test pain change ( p<0.001 ) . The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes . However , the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis . METHODS STUDY DESIGN 24-month prospect i ve r and omized controlled study . PATIENTS Out patients with painful medial femoro-tibial knee osteoarthritis . OUTCOME MEASURES Patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis , with the last observation carried forward ( LOCF ) . Main symptomatic criterion : Improvement in the patient 's assessment of activity ( defined as a reduction of one grade or more at the end of the study as compared to baseline , and no intra-articular injection or lavage during the 6 months previous to the last visit ) . Secondary criteria for assessment : ( a ) Changes in the WOMAC subscales at month 24 , and ( b ) concomitant therapies ( analgesics , NSAIDs and intra-articular injections or lavages ) . Structural criterion : Joint space width ( JSW ) at the narrowest point . Non-compliance was defined as intermittent or lack of insole fitting at two consecutive visits . Compliance within groups was compared by using a life table analysis technique ( Log-Rank ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the 2 treatment groups . At year 2 , there was no statistically significant difference between the 2 groups concerning the percentages of patients with improvement in both global assessment of disease activity and in WOMAC subscales ( pain , stiffness , function ) . The number of days with NSAIDs intake was lower in the group with laterally wedged insoles than in the neutrally wedged group ( 71+/-173 days vs. 127+/-193 days , P=0.003 , Mann-Whitney test ) . The mean joint space narrowing rate did not differ between the two groups : 0.21+/-0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the neutrally wedged group . Compliance and tolerance were satisfactory . Compliance was different between the 2 groups at month 24 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 85.8 % vs 71.9 % , P=0.023 ) . CONCLUSION This study failed to demonstrate a relevant symptomatic and /or structural effect of laterally-wedged insoles in medial femoro-tibial OA . However , the reduced NSAIDs intake and the better compliance in the treatment group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA BACKGROUND Non-pharmacological therapies are recommended for the care of knee osteoarthritis patients . Unloader knee braces provide an interesting functional approach , which aims to modulate mechanical stress on the symptomatic joint compartment . We aim ed to confirm the biomechanical effects and evaluate functional benefits of a new knee brace that combines a valgus effect with knee and tibial external rotation during gait in medial osteoarthritis patients . METHODS Twenty patients with unilateral symptomatic medial knee osteoarthritis were included and they performed two test sessions of 3D gait analysis with and without the brace at the initial evaluation ( W0 ) and after 5weeks ( W5 ) of wearing the brace . VAS-pain , satisfaction scores , WOMAC scores , spatio-temporal gait parameters ( gait speed , stride length , stance and double stance phases , step width ) , and biomechanical data of the ipsilateral lower limb ( hip , knee , ankle and foot progression angles ) were recorded at each session . RESULTS VAS-pain and WOMAC significantly decreased at W5 . Walking speed was not significantly modified by knee bracing at W0 , but increased significantly at W5 . Knee adduction moments and foot progression angles significantly decreased in the terminal stance and push off , respectively , with bracing at W0 and W5 . Lower-limb joint angles , moments and powers were significantly modified by wearing the brace at W0 and W5 . CONCLUSION This new knee brace with distraction-rotation effects significantly alters knee adduction moments and foot progression angles during gait , which might lead to significant functional gait improvements and have carry-over effects on pain at the short term in osteoarthritis patients ( < 2 months ) . LEVEL OF EVIDENCE level IV Knee osteoarthritis ( OA ) is associated with quadriceps atrophy and weakness , so muscle strengthening is an important point in the rehabilitation process . Since pain and joint stiffness make it often difficult to use conventional strength exercises , neuromuscular electrical stimulation ( NMES ) may be an alternative approach for these patients . This study was aim ed at ( 1 ) identifying the associations of knee OA with quadriceps muscle architecture and strength , and ( 2 ) quantifying the effects of a NMES training program on these parameters . In phase 1 , 20 women with knee OA were compared with 10 healthy female , asymptomatic , age-matched control subjects . In phase 2 , 12 OA patients performed an 8-week NMES strength training program . OA patients presented smaller vastus lateralis thickness ( 11.9 mm ) and fascicle length ( 20.5 % ) than healthy subjects ( 14.1 mm ; 24.5 % ) , and also had a 23 % smaller knee extensor torque compared to the control group . NMES training increased vastus lateralis thickness ( from 12.6 to 14.2 mm ) and fascicle length ( from 19.6 % to 24.6 % ) . Additionally , NMES training increased the knee extensor torque by 8 % and reduced joint pain , stiffness , and functional limitation . In conclusion , OA patients have decreased strength , muscle thickness , and fascicle length in the knee extensor musculature compared to control subjects . NMES training appears to offset the changes in quadriceps structure and function , as well as improve the health status in patients with knee OA Background Quadriceps femoris muscle ( QFM ) weakness is a feature of knee osteoarthritis ( OA ) and exercise programs that strengthen this muscle group can improve function , disability and pain . Traditional supervised resistance exercise is however re source intensive and dependent on good adherence which can be challenging to achieve in patients with significant knee OA . Because of the limitations of traditional exercise programs , interest has been shown in the use of neuromuscular electrical stimulation ( NMES ) to strengthen the QFM . We conducted a single-blind , prospect i ve r and omized controlled study to compare the effects of home-based resistance training ( RT ) and NMES on patients with moderate to severe knee OA . Methods 41 patients aged 55 to 75 years were r and omised to 6 week programs of RT , NMES or a control group receiving st and ard care . The primary outcome was functional capacity measured using a walk test , stair climb test and chair rise test . Additional outcomes were self-reported disability , quadriceps strength and cross-sectional area . Outcomes were assessed pre- and post-intervention and at 6 weeks post-intervention ( weeks 1 , 8 and 14 respectively ) . Results There were similar , significant improvements in functional capacity for the RT and NMES groups at week 8 compared to week 1 ( p≤0.001 ) and compared to the control group ( p < 0.005 ) , and the improvements were maintained at week 14 ( p≤0.001 ) . Cross sectional area of the QFM increased in both training groups ( NMES : + 5.4 % ; RT : + 4.3 % ; p = 0.404 ) . Adherence was 91 % and 83 % in the NMES and RT groups respectively ( p = 0.324 ) . Conclusions Home-based NMES is an acceptable alternative to exercise therapy in the management of knee OA , producing similar improvements in functional capacity . Trial registration : Current Controlled Trials IS RCT Background Neuromuscular electrical stimulation ( NMES ) has demonstrated efficacy in improving quadriceps muscle strength ( force-generating capacity ) and activation following knee replacement and ligamentous reconstruction . Yet , data are lacking to establish the efficacy of NMES in people with evidence of early radiographic osteoarthritis . Objective The purpose of this study was to determine whether NMES is capable of improving quadriceps muscle strength and activation in women with mild and moderate knee osteoarthritis . Design This study was a r and omized controlled trial . Methods Thirty women with radiographic evidence of mild or moderate knee osteoarthritis were r and omly assigned to receive either no treatment ( st and ard of care ) or NMES treatments 3 times per week for 4 weeks . The effects of NMES on quadriceps muscle strength and activation were evaluated upon study enrollment , as well as at 5 and 16 weeks after study enrollment , which represent 1 and 12 weeks after cessation of NMES among the treated participants . The Western Ontario and McMaster Universities Osteoarthritis Index and a 40-foot ( 12.19-m ) walk test were used at each testing session . Results Improvements in quadriceps muscle strength or activation were not realized for the women in the intervention group . Quadriceps muscle strength and activation were similar across testing sessions for both groups . Limitations Women were enrolled based on radiographic evidence of osteoarthritis , not symptomatic osteoarthritis , which could have contributed to our null finding . A type II statistical error may have been committed despite an a priori power calculation . The assessor and the patients were not blinded to group assignment , which may have introduced bias into the study . Conclusions Four weeks of NMES delivered to women with mild and moderate osteoarthritis and mild strength deficits was insufficient to induce gains in quadriceps muscle strength or activation . Future research is needed to examine the dose-response relationship for NMES in people with early radiographic evidence of osteoarthritis OBJECTIVE To assess the efficacy of medial-wedge insoles in valgus knee osteoarthritis ( OA ) . METHODS Thirty consecutive women with valgus-deformity knee OA > or = 8 degrees were r and omized into 2 groups : medial insole ( insoles with 8-mm medial elevation at the rearfoot [ n = 16 ] ) and neutral insole ( similar insole without elevation [ n = 14 ] ) . Both groups also wore ankle supports . A blinded examiner assessed pain on movement , at rest , and at night with a visual analog scale ( VAS ) , the Lequesne index , and Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) Index . Femorotibial , talocalcaneal , and talar tilt angles were evaluated at baseline and after 8 weeks of insole use . RESULTS Significant reductions in the medial insole group were observed for pain on movement ( mean + /- SD VAS pre- and postintervention 8.1 + /- 1.5 versus 4.2 + /- 2.4 ; P = 0.001 ) , at rest ( 5.1 + /- 2.3 versus 2.7 + /- 2.4 ; P = 0.002 ) , and at night ( 6.1 + /- 2.7 versus 3.1 + /- 2.1 ; P = 0.001 ) . In addition , a decrease in Lequesne ( 14.7 + /- 3.4 versus 9.6 + /- 3.8 ; P = 0.001 ) and WOMAC scores ( 74.1 + /- 14.2 versus 56.1 + /- 14.9 ; P = 0.001 ) was observed for the medial insole group . In the neutral insole group , a significant reduction was observed only for night pain ( mean + /- SD VAS pre- and postintervention 5.8 + /- 2.4 versus 4.6 + /- 2.4 ; P = 0.019 ) . An increase in femorotibial angle ( 169.0 + /- 3.4 versus 170.8 + /- 3.7 ; P = 0.001 ) occurred only in the medial insole group . Moreover , the difference in measured femorotibial angles pre- and postintervention was 1.84 + /- 1.42 versus -0.18 + /- 0.67 ( P < 0.001 ) for the medial and neutral insole groups . CONCLUSION The use of medial-wedge insoles was highly effective in reducing pain at rest and on movement and promoted a functional improvement of valgus knee OA Cetin N , Aytar A , Atalay A , Akman MN : Comparing hot pack , short-wave diathermy , ultrasound , and TENS on isokinetic strength , pain , and functional status of women with osteoarthritic knees : a single-blind , r and omized , controlled trial . Am J Phys Med Rehabil 2008;87:443–451 . Objective : To investigate the therapeutic effects of physical agents administered before isokinetic exercise in women with knee osteoarthritis . Design : One hundred patients with bilateral knee osteoarthritis were r and omized into five groups of 20 patients each : group 1 received short-wave diathermy + hot packs and isokinetic exercise ; group 2 received transcutaneous electrical nerve stimulation + hot packs and isokinetic exercise ; group 3 received ultrasound + hot packs and isokinetic exercise ; group 4 received hot packs and isokinetic exercise ; and group 5 served as controls and received only isokinetic exercise . Results : Pain and disability index scores were significantly reduced in each group . Patients in the study groups had significantly greater reductions in their visual analog scale scores and scores on the Lequesne index than did patients in the control group ( group 5 ) . They also showed greater increases than did controls in muscular strength at all angular velocities . In most parameters , improvements were greatest in groups 1 and 2 compared with groups 3 and 4 . Conclusions : Using physical agents before isokinetic exercises in women with knee osteoarthritis leads to augmented exercise performance , reduced pain , and improved function . Hot pack with a transcutaneous electrical nerve stimulator or short-wave diathermy has the best outcome OBJECTIVE To assess immediate effects of laterally wedged insoles on walking pain , external knee adduction moment , and static alignment , and whether these immediate effects together with age , body mass index , and disease severity predict clinical outcome after 3 months of wearing insoles in medial knee osteoarthritis . METHODS Forty volunteers ( mean age 64.7 years , 16 men ) were tested in r and om order with and without a pair of 5 degrees full-length lateral wedges . Immediate changes in static alignment were measured via radiographic mechanical axis and changes in adduction moment via 3-dimensional gait analysis . After 3 months of treatment with insoles , changes in pain and physical functioning were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and patient-perceived global change scores . RESULTS Reductions in the adduction moment occurred with insoles ( first peak mean [ 95 % confidence intervals ( 95 % CI ) ] -0.22 [ -0.28 , -0.15 ] Nm/body weight x height % ) , accompanied by a reduction in walking pain of approximately 24 % ( mean [ 95 % CI ] -1.0 [ -4.0 , 2.0 ] ) . Insoles had no mean effect on static alignment . Mean improvement in WOMAC pain ( P = 0.004 ) and physical functioning ( mean [ 95 % CI ] -6 [ -11 , -1 ] ) was observed at 3 months , with 25 ( 69 % ) and 26 ( 72 % ) of 36 individuals reporting global improvement in pain and functioning , respectively . Regression analyses demonstrated that disease severity , baseline functioning , and magnitude of immediate change in walking pain and the first peak adduction moment with insoles were predictive of clinical outcome at 3 months . CONCLUSION Lateral wedges immediately reduced knee adduction moment and walking pain but had no effect on static alignment . Although some parameters predicted clinical outcome , these explained only one-third of the variance , suggesting that other unknown factors are also important OBJECTIVE This is a double blind study that examined the optimal stimulation frequency of transcutaneous electrical nerve stimulation in reducing pain due to knee osteoarthritis . SUBJECTS Thirty-four subjects were r and omly allocated into 4 groups receiving transcutaneous electrical nerve stimulation at either : ( i ) 2 Hz ; ( ii ) 100 Hz ; ( iii ) an alternating frequency of 2 Hz and 100 Hz ( 2/100 Hz ) ; or ( iv ) a placebo transcutaneous electrical nerve stimulation . METHODS Treatment was administered 5 days a week for 2 weeks . The outcome measures included : ( i ) a visual analogue scale ; ( ii ) a timed up- and -go test ; and ( iii ) a range of knee motion . RESULTS The 3 active transcutaneous electrical nerve stimulation groups ( 2 Hz , 100 Hz , 2/100 Hz ) , but not the placebo group , significantly reduced osteoarthritic knee pain across treatment sessions . However , no significant between-group difference was found . Similarly , the 3 active transcutaneous electrical nerve stimulation groups , but not the placebo group , produced significant reductions in the amount of time required to perform the timed up- and -go test , and an increase in the maximum passive knee range of motion . CONCLUSION Our findings suggested that 2 weeks of repeated applications of transcutaneous electrical nerve stimulation at 2 Hz , 100 Hz or 2/100 Hz produced similar treatment effects for people suffering from osteoarthritic knee CONTEXT AND OBJECTIVE Neuromuscular electrical stimulation ( NMES ) has been used in rehabilitation protocol s for patients suffering from muscle weakness result ing from knee osteoarthritis . The purpose of the present study was to assess the effectiveness of an eight-week treatment program of NMES combined with exercises , for improving pain and function among patients with knee osteoarthritis . DESIGN AND SETTING R and omized clinical trial at Interlagos Specialty Ambulatory Clinic , Sao Paulo , Brazil . METHODS One hundred were r and omized into two groups : NMES group and control group . The following evaluation measurements were used : numerical pain scale from 0 to 10 , timed up and go ( TUG ) test , Lequesne index and activities of daily living ( ADL ) scale . RESULTS Eighty-two patients completed the study . From intention-to-treat ( ITT ) analysis comparing the groups , the NMES group showed a statistically significant improvement in relation to the control group , regarding pain intensity ( difference between means : 1.67 [ 0.31 to 3.02 ] ; P = 0.01 ) , Lequesne index ( difference between means : 1.98 [ 0.15 to 3.79 ] ; P = 0.03 ) and ADL scale ( difference between means : -11.23 [ -19.88 to -2.57 ] ; P = 0.01 ) . CONCLUSION NMES , within a rehabilitation protocol for patients with knee osteoarthritis , is effective for improving pain , function and activities of daily living , in comparison with a group that received an orientation program . CLINICAL TRIAL REGISTRATION ACTRN012607000357459 Some have proposed the use of transcutaneous electrical nerve stimulation ( TENS ) as an adjunct to the current st and ard of care in treatment of osteoarthritis knee pain . The purpose of this study was to evaluate the effects of TENS on the following issues in patients who have early-stage osteoarthritis of the knee : ( 1 ) pain reduction ; ( 2 ) subjective and ( 3 ) objective functional improvements ; ( 4 ) quality -of-life ( QOL ) measure improvements ; and ( 5 ) isokinetic strength . A prospect i ve , r and omized , and single-blinded trial was performed on 23 patients who were r and omized to either novel TENS device or st and ard of care . Metrics analyzed included stair-climb test ; timed-up- and -go test ( TUGT ) ; 2-minute walk test ; 20 times , single leg 6-inch step test ; five-repetition chair-rise test ; active and passive range-of-motion ( ROM ) score ; short form health survey-36 scores ( SF-36 ) score ; Knee Society Score ( KSS ) ; lower extremity functional scale ( LEFS ) ; visual analog scale ( VAS ) ; and isokinetic quadriceps and hamstring strength . In objective functional scores , TENS had significant improvements in TUGT and objective KSS when compared with the matching cohort . Subjective functional and QOL outcomes patients had a significant improvement of their LEFS and SF-36 physical component with the use of TENS brace . The TENS device significantly improved the quadriceps strength when compared with st and ard therapy . In evaluation for improvement within the TENS cohort , patients had a significant improvement at 3-month follow-up in the TUG test , timed stair-climb test , 20-times single leg , KSS , LEFS , and SF-36 physical component compared to their initial visit . In addition , within the TENS cohort , patients had a significant reduction in pain via VAS at their 3-month follow-up . In conclusion , the use of TENS for 3 months has shown encouraging results to improve pain , function , and QOL in patients with painful osteoarthritic knees , and could positively contribute as an adjunct to current nonoperative treatment of knee arthritis . However , given our small sample size , larger r and omized studies are needed to further evaluate these outcomes The objective of this study was to examine the short- and long-term effects of a home-based , 12-week neuromuscular electrical stimulation ( NMES ) of the quadriceps femoris to decrease arthritis knee pain in older adults with osteoarthritis of the knee . The study sample ( N = 38 ) was r and omly assigned to the NMES treatment plus education group or the arthritis education-only group . Pain was measured in both groups with the McGill Pain Question naire ( MPQ ) at baseline , during the intervention at weeks 4 , 8 , 12 , and at follow-up and with the Arthritis Impact Measurement Scale 2-Pain Subscale ( AIMS 2-PS ) at baseline and week 12 . The NMES Pain Diary ( PD ) was completed 15 minutes before and after each stimulation session . There was a significant 22 % decline in pain 15 minutes after as compared with immediately before each NMES treatment ( p < .001 ) , as measured by the PD . No significant group differences were found between the 2 groups over the course of the intervention and follow-up . These findings indicate that a home-based NMES intervention reduced arthritis knee pain 15 minutes after a NMES treatment Background : Patients suffering from medial compartment knee osteoarthritis ( OA ) may be treated with unloader knee orthoses or laterally wedged insoles . Objectives : The aim of this study was to identify and compare the effects of them on the gait parameters and pain in these patients . Study Design : Quasi-experimental . Methods : Volunteer subjects with medial compartment knee OA ( n = 24 , mean age 59.29 ± 2.23 years ) were r and omly assigned to two separate groups and evaluated when wearing an unloader knee orthosis or insoles incorporating a 6 ° lateral wedge . Testing was performed at baseline and after six weeks of each orthosis use . A visual analog scale score was used to assess pain and gait analysis was utilized to determine gait parameters . Results : Both orthoses improved all parameters compared to the baseline condition ( p = 0.000 ) . However , no significant differences in pain ( p = 0.649 ) , adduction moment ( p = 0.205 ) , speed of walking ( p = 0 . 056 ) or step length ( p = 0.687 ) were demonstrated between them . The knee range of motion ( p = 0.000 ) were significantly different between the two interventions . Conclusion : Both orthoses reduced knee pain . Maximum knee range of motion was increased by both interventions although it was 3 degrees less when wearing the knee orthosis . Clinical relevance Both orthoses reduce pain and improve gait anomalies in medial compartment knee OA . Our results suggest a laterally wedged insole can be an alternative conservative approach to unloader knee orthosis for treating symptoms of medial compartment knee OA Objective : To determine whether neuromuscular electrical stimulation applied to the quadriceps femoris muscle will enhance the effectiveness of an exercise programme in patients with knee osteoarthritis . Design : A r and omized trial with parallel intervention treatment groups . Setting : Outpatient physical therapy clinic . Subjects : Fifty participants ( mean age ( SD ) 68.9 ( 7.7 ) years ) with symptomatic idiopathic knee osteoarthritis and radiographic evidence ( grade ≥II Kelgren ’s classification ) . Interventions : Participants were r and omized into one of two groups receiving 12 biweekly treatments : An exercise-only group or an exercise combined with neuromuscular electrical stimulation group ( biphasic pulses , at 75 Hz and 250 µs phase duration ) . Main measures : Knee pain intensity ; maximal voluntary isometric contraction and voluntary activation of the quadriceps femoris muscle ; measures of functional performance . Results : A significant interaction effect ( P = 0.01 ) indicated greater improvement in pain for the electrical stimulation group . The mean ( SD ) change in pain intensity was from 7.5 ± 2 to 5 ± 2.2 and from 7.4 ± 1.9 to 3.3 ± 2.4 in the exercise and electrical stimulation groups , respectively . A significant treatment effect was also noted for the voluntary activation of the quadriceps femoris , which increased by 22.2 % in the electrical stimulation group and by 9.6 % in the exercise group ( P = 0.045 ) . Significant improvements were observed in both groups in all remaining measures , with no differences between groups . Conclusions : Electrical stimulation treatment to the quadriceps femoris enhanced the effectiveness of an exercise programme in alleviating pain and improving voluntary activation in patients with knee osteoarthritis , but did not enhance its effect on muscle strength or functional performance OBJECTIVES To examine the effectiveness of shock-absorbing insoles in the immediate reduction of knee joint load , as well as reductions in knee joint load , pain , and dysfunction after 1 month of wear , in individuals with knee osteoarthritis ( OA ) . DESIGN Pre-post design with participants exposed to 2 conditions ( normal footwear , shock-absorbing insoles ) with a 1-month follow-up . SETTING University laboratory for testing and general community for intervention . PARTICIPANTS Community-dwelling individuals ( N=16 ; 6 men , 10 women ) with medial compartment knee OA . INTERVENTION Participants were provided with sulcus length shock-absorbing insoles to be inserted into their everyday shoes . MAIN OUTCOME MEASURES Primary outcome measures included the peak , early stance peak , and late stance peak external knee adduction moment ( KAM ) ; the KAM impulse ( positive area under the KAM curve ) ; and peak tibial vertical acceleration . Secondary outcomes included walking pain , the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale and total score , and a timed stair climb task . RESULTS There was a significant reduction in the late stance peak KAM with shock-absorbing insoles ( P=.03 ) during follow-up compared with the baseline test session . No other immediate or longitudinal significant changes ( P>.05 ) in the other KAM parameters or peak tibial acceleration after use of a shock-absorbing insole were observed . However , significant improvements in all measures of pain and function ( P<.05 ) were observed . CONCLUSIONS Shock-absorbing insoles produced significant reductions in self-reported knee joint pain and physical dysfunction with 1 month of wear in patients with knee OA despite no consistent changes in knee joint load . Further research using r and omized controlled trials , with larger sample sizes and explorations into long-term use of shock-absorbing insoles and their effect on disease progression , is warranted |
505 | 18,432,435 | Apart from one ( no autocorrection , symmetric exercises , very low method ological quality ) , all studies confirmed the efficacy of exercises in reducing the progression rate ( mainly in early puberty ) and /or improving the Cobb angles ( around the end of growth ) .
Exercises were also shown to be effective in reducing brace prescription . | BACKGROUND A previously published systematic review ( Ped .
Rehab.2003 - DARE 2004 ) documented the existence of the evidence of level 2a ( Oxford EBM Centre ) on the efficacy of specific exercises to reduce the progression of AIS ( Adolescent Idiopathic Scoliosis ) .
AIM To confirm whether the indication for treatment with specific exercises for AIS has changed in recent years . | AIM Bracing is considered to be effective in the treatment of adolescent idiopathic scoliosis . The concept prevailing today includes an asymmetrical construction , mainly using a mechanical three-point system . We developed the new Sforzesco brace , based on the SPoRT concept ( Symmetric , Patient-oriented , Rigid , Three-dimensional , active ) . The aim of this study is to verify the results of this concept and brace , compared to three-point classical systems . METHODS We performed a prospect i ve , pair-controlled study . It was possible to match 15 patients , out of the first 18 consecutively treated with the Sforzesco brace ( Group SPoRT ) , with previous patients treated with the Lyon brace ( Group LY ) . SPoRT included 14.2+/-1.7 year old patients , with 47+/-7 degrees Cobb worst curves , and 11+/-4 degrees Bunnell ; LY included 13.6+/-1.6 year old patients , with 43+/-7 degrees Cobb and 12+/-5 degrees Bunnell . The brace had to be worn 23 h per day and patients were evaluated after 6 months both clinical ly and radiographically ( without the brace ) . Appropriate statistics were used . RESULTS At the baseline there were slight differences between the groups , with SPoRT worse than LY . All radiographic and clinical parameters decreased significantly with treatment in both groups , apart from thoracic Cobb degrees in LY . SPoRT had better results than LY ( P<0.05 ) radiographically ( worst curve -10+/-5 degrees vs -5+/-7 degrees , all curves -8+/-7 degrees vs -6+/-7 degrees ) , for sagittal profile ( distance from plumbline : T12 -6+/-9 mm vs + 2+/-8 and L3 -7+/-12 vs 0+/-10 ) and aesthetics of the shoulders ( 9 improved and 6 unchanged vs 5 and 8) and waists ( 10 improved and 5 unchanged vs 5 and 8) . Finally , clinical results in terms of patient recovery were better in SPoRT than LY ( 12 improved and 3 unchanged vs 8 and 5 ) . CONCLUSION When a new treatment is introduced , it is not possible to wait years ( end of therapy ) before verifying its utility , and in scoliosis bracing a short term study already gives very important clues . This study confirms the immediate efficacy of brace treatment ( even in such high degree cases ) whatever the brace concept used , with only 2 ( out of 30 ) progressed curves . In SPoRT we had no progressions , and obtained a statistically significant 80 % better radiographic results than LY in the worst scoliosis curve , and 40 % in the average of all curves , as well as improved aesthetics and sagittal profile ( that is crucial in scoliosis bracing ) . The Sforzesco brace should be used , and the SPoRT concept explored in the long term to verify if the classical three-point system should be totally ( or partially ) ab and oned The purpose of the present study was to investigate the effect of aerobic training in girls with idiopathic scoliosis , in selective respiratory parameters ( VC , FVC , FEV1 , FEV1/VC% FEV1/FVC ) as well as the ability to perform aerobic work ( PWC170 ) . The training group consisted of 20 young girls with a mean age of 13.5 + /- 0.16 years . They wore a Boston-type brace for a mean period of 0.30 + /- 0.04 years and suffered from a scoliotic curve ( 27.4 + /- 1.9 degrees ) . They followed a two-month training program on the cycloergometer . Each training session lasted 30 min and was performed four times a week . The control group consisted of 20 girls with a mean age of 13.6 + /- 0.18 years and they wore the same type of brace for a mean period of 0.24 + /- 0.04 years . They also suffered from a scoliosis ( 29.5 + /- 1.8 degrees ) . The results of the study revealed that aerobic training sustained ( VC , FEV1 , FEV1/VC ) or improved significantly ( FVC , FEV1/FVC ) the parameters of pulmonary function , while the respective parameters ( VC , FVC ) for the control group were reduced during the two-month period . The ability to perform aerobic work increased 48.1 % ( P < 0.01 ) in the training group , while it decreased 9.2 % ( P < 0.01 ) in the control group Background The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies . Heterogeneity of the sample s has been suggested as a reason for conflicting results . Besides the obvious theoretical differences between the brace concepts , the variability in the technical factors can also explain the contradictory results between same brace types . This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT . Ultimately , this information could be a foundation for establishing a consensus and framework for future prospect i ve controlled studies . Methods A preliminary question naire on the topic of ' brace action ' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis . A particular case was presented ( main thoracic curve with minor lumbar ) . Several key points emerged and were used to develop a second question naire which was discussed and full filed after the SOSORT consensus meeting ( Milano , Italy , January 2005 ) . Results Twenty-one question naires were completed . The Chêneau brace was the most frequently recommended . The importance of the three point system mechanism was stressed . Options about proper pad placement on the thoracic convexity were divided 50 % for the pad reaching or involving the apical vertebra and 50 % for the pad acting caudal to the apical vertebra . There was agreement about the direction of the vector force , 85 % selecting a ' dorso lateral to ventro medial ' direction but about the shape of the pad to produce such a force . Principles related to three-dimensional correction achieved high consensus ( 80%–85 % ) , but suggested methods of correction were quite diverse . Conclusion This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment . If the goal of a ' treatment consensus ' is realistic and achievable , significantly more effort will be required to reconcile these differences UNLABELLED There is low evidence on the possible efficacy of exercises to treat idiopathic scoliosis , grade d as C by the existing Italian Guidelines . Our aim was to verify if exercises quality has an effect on results . DESIGN Prospect i ve controlled study on idiopathic scoliosis patients that performed only exercises to avoid progression . TREATMENT SEAS Group make exercises according to the protocol SEAS.02 ( Scientific Exercises Approach to Scoliosis , version 2002 ) . The CONT Group performed exercises at a local structure according to different protocol s preferred by the treating therapists . Population . SEAS : 48 patients ( 37 females ) , 12.5+/-2.2 years , 15.1 degrees + /-5.7 degrees Cobb ( degrees C ) , 9.0 degrees + /-3.3 degrees Bunnell ( degrees B ) . The difference in the number of braced patients within the first year has been almost statistically significant ( P=0.07 ) : 1 in SEAS vs. 5 in CONT . Cobb degrees improved with treatment ( P<0.05 ) only in the SEAS group . Clinical results ( variation of at least 5 degrees C or 2 degrees B ) were better in SEAS than CONT . Not all exercises for scoliosis have the same efficacy : this study proves the short term efficacy of SEAS.02 when compared to usual care The r and omized controlled trial is often difficult , impractical or unethical in the clinical setting . Specific types of experimental design are examined for application and ease of interpretation of results , with particular focus on the generalization and demonstration of cause and effect . Examples are given of relatively easy changes that greatly strengthen the design and several recently published studies are used as illustrative examples UNLABELLED The Lyon school has proposed a preparation to brace wearing through an intensive mobilization in order to obtain a better reduction of the braced scoliotic curve . Our aim was to verify this hypothesis . DESIGN A prospect i ve controlled study on consecutive patients having idiopathic scoliosis with brace management . OUTCOME Results after 5 months of brace wearing were review ed by radiographic examination without the brace . TREATMENT SEAS Group exercises according to the protocol SEAS.02 ( Scientific Exercises Approach to Scoliosis , version 2002 ) ; CONT Group various type of exercises . Population . 110 patients ( 34 females ) , 13.5+/-2.4 years , 31.1 degrees + /-11.1 degrees Cobb ( degrees C ) , 14.4 degrees + /-6.0 degrees Bunnell ( degrees B ) . All parameters improved at follow-up in both groups . SEAS had better results than CONT for degrees C. Clinical results ( variations of at least 5 degrees C and 2 degrees B ) were better in SEAS than CONT . This study proves the efficacy of SEAS.02 exercises preparatory for bracing . Bracing demonstrated its short term efficacy The goal of this study is to test the hypothesis that physiotherapy-based intervention can reduce incidence of progression in children with IS . Two independent patient groups matched by age and sex at diagnosis were analysed using the outcome parameter , incidence of progression ( S 5 ° ) . One group was untreated and the other received scoliosis in-patient rehabilitation ( SIR ) . Incidence of progression in groups of untreated patients ranged from 1.5-fold ( 71.2 % vs 46.7 % ) to 2.9-fold ( 55.8 % vs 19.2 % ) higher than in groups of patients treated with SIR , even when SIR-treated groups included patients with more severe curvatures . Statistically , the differences were highly significant . Efforts to test the hypothesis that physical therapies addressing postural imbalance can be used effectively in the treatment of IS have been limited . The results of this study are consistent with the possibility that a supervized programme of exercise-based therapies can reduce incidence of progression in children with IS Abstract A group of 44 patients with idiopathic scoliosis ( mean age 13.6 years ) with an initial Cobb angle between 20 ° and 32 ° received side-shift therapy ( mean treatment duration 2.2 years ) . A group of 120 brace patients ( mean age 13.6 years ) with an initial Cobb angle in the same range ( mean brace treatment 3.0 years ) was the historical reference group . Failure was defined as an increase of Cobb angle greater than 5 ° within 4 months or a Cobb angle greater than 35 ° or a total increase of Cobb angle greater than 10 ° . The chance of success was not significantly different between the side-shift and the brace groups , whether tested for efficiency ( 66 % vs 68 % ) or efficacy ( 85 % vs 90 % ) . The difference in the mean progression of the Cobb angle for the respective groups is small ( for efficiency : 3 ° vs –2 ° , for efficacy : 2 ° vs –1 ° ) . Side-shift therapy appears to be a promising additional treatment for idiopathic scoliosis in adolescents with an inital Cobb angle between 20 ° and 32 ° The possibility of using learned physiological responses in control of progressive adolescent idiopathic scoliosis ( AIS ) was investigated . Sixteen ( 16 ) AIS patients with progressing or high-risk curves ( Cobb 's angle between 25 ° and 35 ° at start and reducible by lateral bending ) were fitted with a device with tone alarm for poor posture . In the first 18 months of application , 3 patients defaulted and 4 showed curve progression > 10 ° ( 2 changed to rigid spinal orthoses and 2 underwent surgery ) . The curves for the other 9 patients were kept under control ( within ±5 ° of Cobb 's angle ) and 5 of them have reached skeletal maturity and terminated the application . The remaining 4 patients were still using the devices until skeletal maturity or curve progression . The curve control rate was 69 % . A long-lasting active spinal control could be achieved through the patient 's own spinal muscles . Nevertheless , before the postural training device could become a treatment modality , a long-term study for more AIS patients was necessary . This project is ongoing in the Duchess of Kent Children 's Hospital , S and y Bay , Hong Kong |
506 | 27,821,401 | The use of DESs significantly improves the above outcomes in CKD patients . | BACKGROUND Drug-eluting stents ( DESs ) and bare metal stents ( BMSs ) are both recommended to improve coronary revascularization and to treat coronary artery disease in patients with chronic kidney disease ( CKD ) .
However , the potential superiority of DESs over BMSs for reducing the incidence of long-term major adverse cardiovascular events and mortality in CKD patients has not been established , and the results remain controversial .
We aim ed to systematic ally assess and quantify the total weight of evidence regarding the use of DESs versus BMSs in CKD patients . | Background — Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results . Drug-eluting stents ( DES ) might reduce the rate of target vessel revascularization in comparison with bare-metal stents ( BMS ) in patients with chronic kidney disease . However , given the multiple concomitant individual variables present in such patients , the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess . Methods and Results — R and omized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease ( RENAL-DES ) was a prospect i ve , r and omized , multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent ( Xience V ) and BMS with an identical design ( Multi-Link Vision ) , both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min ) . The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months . In 215 patients , 512 coronary vessels were successfully treated with the r and omly assigned DES ( n=257 ) or BMS ( n=255 ) . At 1 year , the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7 % ( 95 % confidence interval , 1.1%–5.6 % ) and 11.4 % ( 95 % confidence interval , 7.8 % to 16 % ) , respectively , P<0.001 . For the multivariate analysis , independent predictors of the ischemia-driven target vessel revascularization were BMS implantation ( odds ratio , 4.95 ; 95 % confidence interval , 2.1–11.6 ; P<0.001 ) and vessel size ( odds ratio , 0.32 ; 95 % confidence interval , 0.1–0.7 ; P=0.006 ) . Conclusions — This is the first r and omized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design , in patients who have chronic kidney disease with multivessel coronary artery disease . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00818792 Background Chronic kidney disease ( CKD ) is strongly associated with adverse outcomes after percutaneous coronary intervention ( PCI ) . There are limited data on the effectiveness of drug-eluting stents ( DES ) in patients with CKD . Methodology /Principal Findings Of 3,752 consecutive patients enrolled in the Guthrie PCI Registry between 2001 and 2006 , 436 patients with CKD - defined as a creatinine clearance < 60 mL/min - were included in this study . Patients who received DES were compared to those who received bare metal stents ( BMS ) . Patients were followed for a mean duration of 3 years after the index PCI to determine the prognostic impact of stent type . Study end-points were all-cause death , myocardial infa rct ion ( MI ) , target vessel revascularization ( TVR ) , stent thrombosis ( ST ) and the composite of major adverse cardiovascular events ( MACE ) , defined as death , MI or TVR . Patients receiving DES in our study , by virtue of physician selection , had more stable coronary artery disease and had lower baseline risk of thrombotic or restenotic events . Kaplan-Meier estimates of proportions of patients reaching the end-points were significantly lower for DES vs. BMS for all-cause death ( p = 0.0008 ) , TVR ( p = 0.029 ) and MACE ( p = 0.0015 ) , but not MI ( p = 0.945 ) or ST ( p = 0.88 ) . Multivariable analysis with propensity adjustment demonstrated that DES implantation was an independent predictor of lower rates of all-cause death ( hazard ratio [ HR ] 0.48 , 95 % confidence interval [ CI ] 0.25–0.92 ) , TVR ( HR 0.50 , 95 % CI 0.27–0.94 ) and MACE ( HR 0.62 , 95 % CI 0.41–0.94 ) . Conclusions In a contemporary PCI registry , selective use of DES in patients with CKD was safe and effective in the long term , with lower risk of all-cause death , TVR and MACE and similar risk of MI and ST as compared with BMS . The mortality benefit may be a result of selection bias and residual confounding , or represent a true finding ; a hypothesis that warrants clarification by r and omized clinical trials Background —An observational study determining the long-term impact of chronic kidney disease ( CKD ) on patients undergoing percutaneous coronary intervention at a tertiary cardiac referral center . CKD is associated with poor in-hospital outcomes after percutaneous coronary intervention , but its effect beyond 1 year , particularly in the drug-eluting stent ( DES ) era , has not been reported . Methods and Results —Baseline creatinine was available for 11 953 patients entered into a prospect i ve registry ( April 2000 to September 2007 ) . Patients were stratified : those with or without at least moderate CKD ( creatinine clearance , < 60 mL/min ) . Follow-up data were obtained through linkage to a provincial registry . Kaplan – Meier analysis was performed . Cox multiple-regression analysis identified independent predictors of late mortality and major adverse cardiac events ( MACE ) and examined the association between DES use and late outcomes in the presence or absence of CKD . CKD was present in 3070 patients ( 25.7 % ) . In-hospital mortality and MACE were significantly increased in CKD ( 3.34 % versus 0.44 % , P<0.001 and 5.73 % versus 2.2 % , P<0.001 ) . Survival and MACE-free survival at 7 years were reduced ( 64.5±1.4 % versus 89.4±0.5 % , P<0.001 ; 44.0±1.4 % versus 63.4±0.8 % , P<0.001 ) . CKD was an independent predictor of late mortality and MACE ( hazard ratio [ HR ] : 2.18 , CI : 1.90 to 2.49 , P<0.0001 ; HR : 1.37 , CI : 1.25 to 1.49 , P<0.0001 ) . DES use was associated with a significant reduction in both ( HR : 0.71 , CI : 0.60 to 0.83 , P<0.0001 ; HR : 0.70 , CI : 0.63 to 0.78 , P<0.0001 ) . In patients with CKD , DES use was associated with reduced revascularization ( HR : 0.68 , CI : 0.53 to 0.88 , P=0.004 ) and reduced MACE ( HR : 0.81 , CI : 0.69 to 0.95 , P=0.011 ) but not reduced mortality ( HR : 0.85 , CI : 0.69 to 1.05 , P=0.1 ) . Conclusion —In a large registry of “ all comers ” for percutaneous coronary intervention , CKD was an independent predictor of adverse late outcomes . DES use may be associated with improved long-term outcomes in this high-risk cohort , but further prospect i ve studies are required BACKGROUND Linkage to the US Renal Data System ( USRDS ) registry commonly is used to identify end-stage renal disease ( ESRD ) cases , or kidney failure treated with dialysis or transplantation , but it underestimates the total burden of kidney failure . This study vali date s a kidney failure definition that includes both kidney failure treated and not treated by dialysis or transplantation . It compares kidney failure risk factors and outcomes using this broader definition with USRDS-identified ESRD risk factors and outcomes . STUDY DESIGN Diagnostic test study with stratified r and om sampling of hospitalizations for chart review . SETTING & PARTICIPANTS Atherosclerosis Risk in Communities Study ( n=11,530 ; chart review , n=546 ) . INDEX TEST USRDS-identified ESRD ; treated or untreated kidney failure defined by USRDS-identified ESRD or International Classification of Diseases , Ninth or Tenth Revision , Clinical Modification ( ICD-9-CM/ICD-10-CM ) code for hospitalization or death . REFERENCE TEST For ESRD , determination of permanent dialysis therapy or transplantation ; for kidney failure , determination of permanent dialysis therapy , transplantation , or estimated glomerular filtration rate < 15 mL/min/1.73 m(2 ) . RESULTS During 13 years ' median follow-up , 508 kidney failure cases were identified , including 173 ( 34.1 % ) from the USRDS registry . ESRD and kidney failure incidence were 1.23 and 3.66 cases per 1,000 person-years in the overall population and 1.35 and 6.59 cases per 1,000 person-years among participants older than 70 years , respectively . Other risk-factor associations were similar between ESRD and kidney failure , except diabetes and albuminuria , which were stronger for ESRD . Survivals at 1 and 5 years were 74.0 % and 24.0 % for ESRD and 59.8 % and 31.6 % for kidney failure , respectively . Sensitivity and specificity were 88.0 % and 97.3 % comparing the kidney failure ICD-9-CM/ICD-10-CM code algorithm to chart review ; for USRDS-identified ESRD , sensitivity and specificity were 94.9 % and 100.0 % . LIMITATIONS Some medical charts were incomplete . CONCLUSIONS A kidney failure definition including treated and untreated disease identifies more cases than linkage to the USRDS registry alone , particularly among older adults . Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition AIMS Evaluation of the long-term safety and efficacy of second-generation everolimus-eluting stents ( EES ) versus first-generation sirolimus-eluting stents ( SES ) in acute myocardial infa rct ion ( AMI ) patients . METHODS AND RESULTS Six hundred and twenty-five patients were r and omised ( 2:1 ) to EES or SES in the multicentre XAMI ( XienceV stent vs. Cypher stent in Primary PCI for Acute Myocardial Infa rct ion ) trial . The primary endpoint was cardiac death , non-fatal AMI or any target vessel revascularisation ( TVR ) at one year , with a planned follow-up of three years . At three-year follow-up , the primary endpoint was 8.0 % for EES and 10.5 % for SES ( p=0.30 ) . Cardiac death was low and comparable in both groups ( EES : 2.5 % versus SES : 2.7 % ; p=0.86 ) , as was definite/probable stent thrombosis ( EES : 2.3 % versus SES 3.2 % ; p=0.60 ) . CONCLUSIONS The event rate at three years in this all-comer , r and omised , multicentre AMI trial was low , including stent thrombosis , with no significant difference between first- and second-generation DES . Registration of trial : http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1123 C and i date number : 2869 ; NTR number : NTR1123 BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications , yet the benefits and risks of treatment beyond 1 year are uncertain . METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed . After 12 months of treatment with a thienopyridine drug ( clopidogrel or prasugrel ) and aspirin , patients were r and omly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months ; all patients continued receiving aspirin . The co primary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events ( a composite of death , myocardial infa rct ion , or stroke ) during the period from 12 to 30 months . The primary safety end point was moderate or severe bleeding . RESULTS A total of 9961 patients were r and omly assigned to continue thienopyridine treatment or to receive placebo . Continued treatment with thienopyridine , as compared with placebo , reduced the rates of stent thrombosis ( 0.4 % vs. 1.4 % ; hazard ratio , 0.29 [ 95 % confidence interval { CI } , 0.17 to 0.48 ] ; P<0.001 ) and major adverse cardiovascular and cerebrovascular events ( 4.3 % vs. 5.9 % ; hazard ratio , 0.71 [ 95 % CI , 0.59 to 0.85 ] ; P<0.001 ) . The rate of myocardial infa rct ion was lower with thienopyridine treatment than with placebo ( 2.1 % vs. 4.1 % ; hazard ratio , 0.47 ; P<0.001 ) . The rate of death from any cause was 2.0 % in the group that continued thienopyridine therapy and 1.5 % in the placebo group ( hazard ratio , 1.36 [ 95 % CI , 1.00 to 1.85 ] ; P=0.05 ) . The rate of moderate or severe bleeding was increased with continued thienopyridine treatment ( 2.5 % vs. 1.6 % , P=0.001 ) . An elevated risk of stent thrombosis and myocardial infa rct ion was observed in both groups during the 3 months after discontinuation of thienopyridine treatment . CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent , as compared with aspirin therapy alone , significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding . ( Funded by a consortium of eight device and drug manufacturers and others ; DAPT Clinical Trials.gov number , NCT00977938 . ) OBJECTIVES This study sought to investigate the impact of chronic kidney disease ( CKD ) in patients undergoing percutaneous coronary intervention ( PCI ) for ST-segment elevation myocardial infa rct ion ( STEMI ) with different antithrombotic strategies . BACKGROUND CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI . METHODS HORIZONS-AMI ( Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infa rct ion ) trial was a multicenter , international , r and omized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor ( GPI ) during primary PCI in STEMI . CKD , defined as creatinine clearance < 60 ml/min , was present at baseline in 554 of 3,397 patients ( 16.3 % ) . Patients were followed for 3 years . Net adverse cardiac event ( NACE ) was defined as the composite of death , reinfa rct ion , ischemia-driven target vessel revascularization ( TVR ) , stroke or non-coronary artery bypass grafting (CABG)-related major bleeding . RESULTS Patients with CKD compared with patients without had higher rates of NACE ( 41.4 % vs. 23.8 % , p < 0.0001 ) , death ( 18.7 % vs. 4.4 % , p < 0.0001 ) , and major bleeding ( 19.3 % vs. 6.7 % , p < 0.0001 ) . Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years ( hazard ratio : 1.51 , 95 % confidence interval : 1.21 to 1.87 , p < 0.001 ) . Patients with CKD r and omized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding ( 19.0 % vs. 19.6 % , p = 0.72 ) or death ( 19.0 % vs. 18.4 % , p = 0.88 ) at 3 years . In patients with CKD , there was no difference in the rates of TVR in bare-metal stents ( BMS ) versus drug-eluting stents ( DES ) at 3 years ( 14.1 % vs. 15.1 % , p = 0.8 ) . CONCLUSIONS STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD . In patients with CKD , there appears to be no benefit of bivalirudin compared with heparin + GPI , or DES versus BMS during primary PCI in improving clinical outcomes BACKGROUND The efficacy of sirolimus-eluting stents ( SESs ) has not been established in dialysis patients . METHODS AND RESULTS This study was a non-r and omized observational single-center registry in a community hospital : data for 80 consecutive dialysis patients who underwent percutaneous coronary intervention ( PCI ) with SES were compared with those of a historical group of consecutive 124 dialysis patients treated with bare-metal stents ( BMS ) . After 1 year , the cumulative incidence of major adverse cardiac events ( MACE ) , comprising cardiac death , nonfatal myocardial infa rct ion , stent thrombosis , or target lesion revascularization ( TLR ) , was 25.2 % in the SES group and 38.2 % in the BMS group ( p=0.048 ) . In multivariate analysis , use of SES remained an independent predictor of MACE at 1 year after PCI ( risk ratio 0.70 , 95 % confidence interval 0.52 - 0.93 , p=0.015 ) . Rates of TLR were 21.7 % in the SES group and 30.9 % in the BMS group and ( p=0.15 ) . Subgroup analysis showed that use of SES was effective in patients with small vessels , non-diabetic patients , and patients without highly calcified lesions . CONCLUSIONS In dialysis patients , the implantation of SES was moderately effective in reducing MACE at 1 year after PCI as compared with BMS . However , the TLR rate at 1 year was relatively higher than previously reported Background Percutaneous coronary intervention with bare metal stents ( BMS ) in patients with chronic kidney disease ( CKD ) has shown suboptimal results . Drug-eluting stents ( DESs ) might reduce the incidence of restenosis and therefore of target lesion revascularization in these patients . Of note , in patients with CKD , multiple concomitant individual variables may be responsible for neointimal hyperplasia after coronary stenting , thus making the comparison of BMS and DES in different patient groups difficult . Study design The RENAL-DES is a prospect i ve , r and omized , multicenter , not-sponsored study to directly compare the efficacy in the prevention of clinical restenosis , of everolimus-eluting stent ( Xience V ) and BMS with identical design ( Multilink Vision ) , both implanted in the same patient with multivessel coronary artery disease and CKD in order to obviate the multiple and unpredictable baseline differences . The primary endpoint of the study is 9-month ischemia-driven target vessel revascularization . Sample size The expected primary endpoint rates are 20 % for BMS and 10 % for DES . According to these estimates , with a significant level of 0.05 , a sample size of 194 patients provides an 80 % statistical power . Assuming a 10 % dropout rate , the goal is to enroll 213 patients ( 426 treated vessels ) from five Italian centers . As 20 % of the patients will likely require stent implantation in three vessels , approximately 500 treated vessels will be analyzed . Conclusion This intraindividual , r and omized study will provide , for the first time , data on the efficacy , in the prevention of clinical restenosis , of DES compared to BMS in patients with multivessel coronary artery disease and CKD ( Clinical Trials.gov Identifier : NCT 00818792 ) |
507 | 28,513,785 | The results showed that both SPG and SPG+SBG protocol s of PMP determined stability in the microbiological results along time . | This study aim ed to investigate the differences in the subgingival microbiological outcomes between periodontal patients su bmi tted to a supragingival control ( SPG ) regimen as compared to subgingival scaling and root planing performed combined with supragingival debridement ( SPG + SBG ) intervention during the periodontal maintenance period ( PMP ) . | BACKGROUND / AIM The purpose of the present investigation was to determine the effect of self-performed supragingival plaque removal using either manual ( Crest Complete ) or power ( Braun 3D Plaque Remover ) toothbrushing on supra and subgingival plaque composition . METHODS 47 periodontal maintenance subjects completed this single-blind 6 month longitudinal study . At baseline , sample s of supra and separately subgingival plaque were taken from the mesial aspect of each tooth in each subject using sterile curettes and individually analyzed for their content of 18 bacterial taxa using checkerboard DNA-DNA hybridization . After r and om assignment to groups receiving either a manual ( n=25 ) or power toothbrush ( n=22 ) , subjects received instruction in oral hygiene and used their assigned toothbrush 2x daily for 6 months . Clinical monitoring and microbiological sampling were repeated at 3 and 6 months . Significant differences in microbiological measures over time were sought using the Quade test and between brushing groups at each time point using the Mann-Whitney test . RESULTS Mean total counts were significantly reduced for supra- and subgingival plaque sample s in the manual group and subgingival sample s in the powered brushing group . Actinomyces naeslundii and Actinomyces israelii/gerencseriae were the most numerous organisms detected at baseline and showed the greatest reductions in counts in both brushing groups . Streptococcus constellatus/intermedius was significantly reduced in both groups , while Streptococcus mitis/oralis/sanguis was significantly reduced in the manual toothbrushing group . Mean counts of species were more markedly altered in subgingival plaque . Major reductions occurred in both groups for A. naeslundii , A. israelii/gerencseriae , Peptostreptococcus micros , Veillonella parvula , Prevotella intermedia/nigrescens , S. mitis/oralis/sanguis and S. constellatus/intermedius . All taxa examined were reduced in prevalence ( % of sites colonized ) in the subgingival plaque sample s for both brushing groups . The reductions in prevalence were greater for A. naeslundii , S. constellatus/intermedius , V. parvula , A. israelii/gerencseriae , S. mitis/oralis/sanguis , P. micros , Streptococcus mutans and P. intermedia/nigrescens . Mean prevalence was decreased more for Porphyromonas gingivalis , Campylobacter rectus/showae , Treponema denticola and Bacteroides forsythus in supragingival plaque than subgingival plaque . CONCLUSIONS The major finding was the effect of supragingival plaque removal on the composition of the subgingival microbiota . Counts and prevalence of most taxa examined were markedly decreased in both toothbrushing groups . This reduction should translate to a decreased risk of periodontal disease initiation or recurrence . Further , the decreased prevalence of periodontal pathogens in supragingival plaque lowers potential reservoirs of these species OBJECTIVE To compare the short-term performance of subgingival local delivery of 2 % minocycline gel and conventional subgingival debridement in supportive periodontal therapy ( SPT ) patients . METHODS Forty adult patients having completed active treatment for moderate to advanced chronic periodontitis were included in a r and omized , controlled , single masked maintenance care pilot study . Sites with residual pocket probing depths > or = 5 mm and bleeding on probing were treated with either minocycline gel ( minocycline-group ) or scaling and root planing only ( debridement-group ) at baseline , 3 , 6 , and 9 months . Clinical and microbiological examinations were performed at baseline , 3 , 6 , 9 , and 12 months . RESULTS Full-mouth plaque and bleeding scores remained < 10 % and < 20 % , respectively , for both groups throughout the study . In both groups there was a persistent reduction in number of teeth and sites with probing pocket depths > or = 5 mm ( p<0.05 ) with no significant differences between the groups . The prevalence of Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , Actinobacillus actinomycetemcomitans , Prevotella intermedia , and Prevotella nigrescens , remained at levels < or = 10(5 ) in the majority of patients and sites in both groups . CONCLUSION This pilot study failed to show a difference between local delivery of 2 % minocycline gel as mono-therapy and traditional subgingival debridement in patients on SPT AIM The objective of this r and omized , controlled clinical trial was to compare the clinical and microbiological effects of pocket debridement using erbium-doped : yttrium , aluminium and garnet ( Er : YAG ) laser with conventional debridement in maintenance patients . MATERIAL & METHODS Fifteen patients , all smokers , having at least four teeth with residual probing depth ( PD ) ≥ 5 mm were recruited . Two pockets in two jaw quadrants were r and omly assigned to subgingival debridement using an Er : YAG laser ( test ) or ultrasonic scaler/curette ( control ) at 3-month intervals . Relative attachment level ( RAL ) , PD , bleeding on probing and dental plaque were recorded at baseline and at 6 and 12 months . Microbiological subgingival sample s were taken at the same time points and analysed using a checkerboard DNA-DNA hybridization technique . RESULTS A significant decrease in PD took place in both treatments from baseline to 12 months ( p < 0.01 ) . In the control , the mean initial PD decreased from 5.4 to 4.0 mm at 12 months . For the test , a similar decrease occurred . No significant between-treatment differences were shown at any time point . The mean RAL showed no overall significant inter- or intra-treatment differences ( p > 0.05 ) . No significant between-treatment differences were observed in subgingival microbiological composition or total pathogens . CONCLUSION The results failed to support that an Er : YAG laser may be superior to conventional debridement in the treatment of smokers with recurring chronic inflammation . This appears to be the first time that repeated Er-YAG laser instrumentation has been compared with mechanical instrumentation of periodontal sites with recurring chronic inflammation over a clinical ly relevant time period Objectives To evaluate repeated subgingival air-polishing in residual pockets with a new erythritol powder containing 0.3 % chlorhexidine . Material and Methods Single-centre , examiner masked , r and omized clinical trial of 12 months with a two-arm , within-subject parallel design . Fifty patients in periodontal maintenance were monitored in 3-month intervals . At months 0 , 3 , 6 and 9 , all sites presenting with a probing depth ( PD ) > 4 mm were subject to subgingival air-polishing ( test side ) or ultrasonic debridement ( control side ) . The primary endpoint was presence/absence of PD > 4 mm after 12 months . Results Totally 6918 sites were monitored at baseline , 457 of them had a PD > 4 mm ( range 5–9 mm ) . The number of pockets > 4 mm per subject , PD and bleeding on probing were significantly lower at month 12 . Differences between test and control were not significant . There was a significant difference in favour of air-polishing for the perception of pain/discomfort . Differences of frequencies at > 1000 and > 100,000 cells/ml of six microorganisms between baseline and month 12 were not significant . At month 12 , test sites were less frequently positive for Aggregatibacter actinomycetemcomitans at > 1000 cells/ml than controls , and counts never exceeded 100,000 cells/ml . Conclusions Repeated subgingival air-polishing reduced the number of pockets > 4 mm similar to ultrasonic debridement . It was safe and induced less pain Recent pre clinical and clinical data have suggested the potential benefit of photodynamic therapy ( PDT ) in the treatment of periodontitis . However , currently , there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis . The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy . Twenty-four patients receiving regularly supportive periodontal therapy were r and omly treated with either subgingival scaling and root planing followed by a single episode of PDT ( test ) or subgingival scaling and root planing alone ( control ) . The following parameters were evaluated at baseline and at 3 months and 6 months after therapy : full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , bleeding on probing ( BOP ) at experimental sites , probing pocket depth ( PPD ) , gingival recession ( REC ) , and clinical attachment level ( CAL ) . Primary outcome variables were changes in PPD and CAL . Microbiological evaluation of Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , Prevotella intermedia ( P.i . ) , Tannerella forsythensis ( T.f . ) , Treponema denticola ( T.d . ) , Peptostreptococcus micros ( P.m . ) , Fusobacterium nucleatum ( F.n . ) , Campylobacter rectus ( C.r . ) , Eubacterium nodatum ( E.n . ) , Eikenella corrodens ( E.c . ) , and Capnocytophaga species ( C.s . ) was also performed at baseline and at 3 months and 6 months after therapy , using a commercially available polymerase chain reaction test . No differences in any of the investigated parameters were observed at baseline between the two groups . At 3 months and 6 months after treatment , there were no statistically significant differences between the groups in terms of PPD , CAL and FMPS . At 3 months and 6 months , a statistically significantly higher improvement of BOP was found in the test group . At 3 months after therapy , the microbiological analysis showed a statistically significant reduction of F.n . and E.n . in the test group . At 6 months , statistically significantly higher numbers of E.c . and C.s . were detected in the test group . The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PPD reduction and CAL gain , but it result ed in significantly higher reduction of bleeding scores than following scaling and root planing alone BACKGROUND This study assessed the long-term effects of adjunctive antimicrobial therapy on periodontal disease progression and oral colonization . METHODS Patients with previously untreated chronic periodontitis and subgingival Actinobacillus actinomycetemcomitans and /or Porphyromonas gingivalis were r and omly assigned to subgingival scaling without ( control group ) or with systemic amoxicillin plus metronidazole and CHX irrigation ( test group ) . Relative attachment levels were determined and subgingival and mucosal plaque sample s were taken at baseline , at 10 days ( plaque only ) and at 3 , 6 , 9 , 12 , 18 , and 24 months following initial therapy . During maintenance therapy , patients received supragingival debridement only . RESULTS After 24 months , the 18 test group patients showed at sites with initial probing depths ( PD ) > or = 7 mm a significantly ( P < 0.05 ) higher frequency of 2 mm or more attachment gain ( 37.3 % + /- 4.6 % ) and lower frequency of attachment loss ( 7.2 % + /- 3.1 % ) compared to the 17 controls ( 8.2 % + /- 3.9 % and 19.1 % + /- 13.1 % , respectively ) . Compared to controls , the intraoral prevalence of A. actinomycetemcomitans ( up to 18 months ) and P. gingivalis ( up to 3 months ) decreased and that of Eikenella corrodens ( at 10 days ) increased in test patients ( P < 0.05 ) . In both treatment groups , the detection frequency of Tannerella forsythensis decreased transiently , while an overall increase was recorded for Treponema ssp . CONCLUSIONS Over the 24-month period , a single course of the administered adjunctive antimicrobial therapy led to a relative risk reduction of 62 % for attachment loss at deep sites . However , with the exception of A. actinomycetemcomitans , it failed to induce long-term changes in the prevalence profiles of oral colonization The present study evaluated the long-term effect of ( i ) meticulous self-performed , supragingival plaque control and ( ii ) the use of a triclosan/copolymer containing dentifrice in adult subjects susceptible to destructive periodontitis . 40 individuals were recruited into the trial . 3 - 5 years prior to the baseline examination , they had all been treated by nonsurgical means- for advanced periodontal disease . During the subsequent maintenance phase , all subjects had at different time intervals exhibited sites with recurrent periodontitis . At a baseline examination , 6 surfaces per tooth were examined regarding bleeding on probing , probing pocket depth , and probing attachment level . The deepest pocket site in each quadrant ( i.e. 4 sites per subject ) was selected and sample s of the subgingival bacteria were taken . At baseline , all volunteers received detailed information on proper oral hygiene techniques . This information was repeated on an individual need basis during the course of the subsequent 36-months . No professional subgingival therapy was delivered between the baseline and the 36-month examinations . The subjects were r and omly distributed into 2 equal groups of 20 individuals each , 1 test and 1 control group . The members of the test group were supplied with a fluori date d dentifrice containing triclosan/copolymer ( Total , Colgate ) , while the controls received a corresponding dentifrice but without triclosan/copolymer . The findings demonstrated that in subjects with advanced and recurrent periodontitis , carefully practice d supragingival plaque control had some effects on the subgingival microbiota , but also that this was insufficient to prevent disease progression . In a corresponding group of subjects , however , who used a triclosan/copolymer dentifrice , the subgingival microbiota was reduced in both quantitative and qualitative terms and recurrent periodontitis was almost entirely prevented The purpose of this study was to evaluate the presence of A. actinomycetemcomitans , P. gingivalis , P. intermedia , E. corrodens and F. nucleatum in 30 subjects with chronic periodontitis treated by scaling and root planing ( SRP ) plus minocycline ( test group ) during 12 months with regular trimester maintenance care . Additionally , we evaluated whether the beneficial effects of the therapy on the microbial flora persisted for 24 months . The test group ( n = 15 ) and the control group [ SRP plus placebo ( n = 15 ) ] were r and omly assigned . After SRP , subjects received minocycline or placebo at the baseline , and at 3 , 6 , and 9 months at all sites with a periodontal pocket depth ( PD ) of > or= 6 mm . Moreover , two homologous teeth , initially PD > or= 6 mm , were clinical ly and microbially monitored by PCR at the baseline , and at 3 , 6 , 9 , 12 and 24 months . Differences in mean PD values between groups were analyzed by Student 's t-test ( P < 0.05 ) . The results for bacterial frequencies showed no significant differences between groups ( Fisher 's Exact test , P < 0.05 ) or between time-points ( Friedman test , P < 0.05 ) . We failed to detect any differences between groups related to the presence of target pathogens for 12 months . The effects of both therapies on the microbial flora did not persist for 24 months . The group without supportive periodontal therapy showed an improvement in the pattern of pathogens with either of the therapies BACKGROUND Chlorhexidine ( CHX ) mouth rinse/spray can still be considered the gold st and ard in the chemical prevention of plaque formation and development of gingivitis . The product unfortunately has some side effects , such as extrinsic tooth staining , poor taste , taste disturbance , sensitivity changes in tongue , pain and irritation because of the alcohol content . These side effects led to the search of new formulations . METHODS In this double-blind , r and omized , long-term , parallel study , 48 moderate periodontitis patients rinsed for 6 months ( starting immediately after a " one-stage , full-mouth " disinfection ) with one of the following products : CHX 0.2%+alcohol ( Corsodyl ) , CHX 0.05%+ cetyl pyridinium chloride ( CPC ) 0.05 % and no alcohol ( Perio-Aid Maintenance , a new formulation ) , or the placebo of the latter . After 1 , 3 and 6 months a series of clinical and microbiological parameters were recorded for the supra- and subgingival area as well as for saliva . RESULTS Although there was a significant treatment impact ( mechanical debridement ) in all groups , both CHX solutions further decreased both plaque and gingivitis indices ( p<0.001 and p<0.05 , respectively ) , when compared with placebo . This was also reflected by additional reductions in the number of CFU/ml of aerobic and especially anaerobic species and by a suppression of Streptococcus mutans ( versus an overgrowth for the placebo ) , in all niches . Differences between both CHX solutions were never encountered . The subjective ratings were slightly in favour of the new CHX-CPC formulation when compared with the other CHX-alcohol formulation , especially for taste of the product ( p<0.05 ) , but less impressive for the staining of teeth and tongue . CONCLUSIONS The results of this study demonstrated the potential of a new CHX 0.05%+CPC 0.05 % non-alcoholic formulation as an effective antiplaque agent for long-term use with reduced subjective side effects AIM A clinical trial was performed to determine ( i ) the initial outcome of non-surgical and surgical access treatment in subjects with advanced periodontal disease and ( ii ) the incidence of recurrent disease during 12 years of maintenance following active therapy . MATERIAL AND METHODS Each of the 64 subjects included in the trial showed signs of ( i ) generalized gingival inflammation , ( ii ) had a minimum of 12 non-molar teeth with deep pockets ( > or = 6 mm ) and with > or = 6 mm alveolar bone loss . They were r and omly assigned to 2 treatment groups ; one surgical ( SU ) and one non-surgical ( SRP ) . Following a baseline examination , all patients were given a detailed case presentation which included oral hygiene instruction . The subjects in SU received surgical access therapy , while in SRP non-surgical treatment was provided . After this basic therapy , all subjects were enrolled in a maintenance care program and were provided with meticulous supportive periodontal therapy ( SPT ) 3 - 4 times per year . Sites that at a recall appointment bled on gentle probing and had a PPD value of > or = 5 mm were exposed to renewed subgingival instrumentation . Comprehensive re-examinations were performed after 1 , 3 , 5 and 13 years of SPT . If a subject between annual examinations exhibited marked disease progression ( i.e. , additional PAL loss of > or = 2 mm at > or = 4 teeth ) , he/she was exited from the study and given additional treatment . RESULTS It was observed that ( i ) surgical therapy ( SU ) was more effective than non-surgical scaling and root planing ( SRP ) in reducing the overall mean probing pocket depth and in eliminating deep pockets , ( ii ) more SRP-treated subjects exhibited signs of advanced disease progression in the 1 - 3 year period following active therapy than SU-treated subjects . CONCLUSION In subjects with advanced periodontal disease , surgical therapy provides better short and long-term periodontal pocket reduction and may lead to fewer subjects requiring additional adjunctive therapy |
508 | 10,796,732 | Lung function measured as forced expired volume in one second ( FEV1 ) was generally better in the treated groups than in control groups but a pooled estimate of effect was not possible .
Resistance to antibiotic increased more in the antibiotic treated group than in placebo group .
REVIEW ER 'S CONCLUSIONS Nebulised anti-pseudomonal antibiotic treatment improves lung function and reduces frequency of exacerbations of infection in people with cystic fibrosis . | BACKGROUND Lung damage associated with persistent infection by Pseudomonas aeruginosa is the major cause of morbidity and mortality in people with cystic fibrosis .
Nebulised antibiotics are commonly used for treatment of this infection .
OBJECTIVES To examine the evidence that nebulised anti-pseudomonal antibiotic treatment in patients with cystic fibrosis reduces frequency of exacerbations of infection , improves lung function , quality of life and survival .
To assess adverse effects of nebulised anti-pseudomonal antibiotic treatment . | Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract , completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo . The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo A r and omized cross-over study was undertaken to compare nebulized ( 1 ) ceftazidime with ( 2 ) a combination of gentamicin and carbenicillin , and ( 3 ) saline , each given for 4 months , in patients with cystic fibrosis infected with Pseudomonas aeruginosa . Mean peak expiratory flow on ceftazidime , 299 litres/min , and on gentamicin and carbenicillin , 297 litres/min , were greater than on saline , 278 litres/min ( P less than 0.02 and P less than 0.05 respectively ) . Similarly mean forced expiratory volume in 1 second on ceftazidime , 1.70 litres , and on gentamicin and carbenicillin , 1.70 litres , were greater than on saline , 1.48 litres ( P less than 0.02 and P less than 0.01 respectively ) . Mean forced vital capacity on gentamicin and carbenicillin , 2.93 litres , was also greater than on saline ( P less than 0.05 ) . We were unable to demonstrate any difference in efficacy between the antibiotic regimens . The patients were admitted to hospital less frequently during the study year compared with the previous year ( P less than 0.05 ) . Sixty-nine per cent of patients had a clinical ly significant ( 20 % ) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study , but a minority of patients appear not to respond to this form of treatment Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis ( CF ) patients during a recent clinical trial of inhaled tobramycin . Impermeability , in which bacteria have reduced susceptibility to all aminoglycosides , was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol . Enzymatic resistance mechanisms were found in fewer than 10 % of resistant isolates . P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness . When enzymatic resistance was involved , all isolates in a group had elevated tobramycin MICs . When impermeability occurred , MICs of a genotypic group varied from susceptible to resistant . These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC STUDY OBJECTIVE To determine the effect of long-term suppression of Pseudomonas aeruginosa on lung function and other clinical end points in adolescent patients with cystic fibrosis ( CF ) . DESIGN Two identical , r and omized , placebo-controlled trials followed by three open-label follow-on trials . SETTING Sixty-nine CF study centers in the United States . INTERVENTIONS Active drug consisting of a 300-mg tobramycin solution for inhalation ( TSI ) . PATIENTS One hundred twenty-eight adolescent CF patients ( aged 13 to 17 years ) with P aeruginosa and mild-to-moderate lung disease ( FEV(1 ) percent predicted > or = 25 % and < or = 75 % ) . MEASUREMENTS Pulmonary function , P aeruginosa colony forming unit density , incidence of hospitalization and IV antibiotic use , weight gain , and aminoglycoside toxicity were monitored . RESULTS At the end of the first three 28-day cycles of TSI treatment , patients originally r and omized to TSI and placebo treatments exhibited improvements in FEV(1 ) percent predicted of 13.5 % and 9.4 % , respectively . FEV(1 ) percent predicted was maintained above the value at initiation of TSI treatment in both groups . At the end of the last " on-drug " period ( 92 weeks ) , patients originally r and omized to TSI and placebo treatments showed improvements of 14.3 % and 1.8 % , respectively . Improvement in pulmonary function was significantly correlated with reduction in P aeruginosa colony forming unit density ( p = 0.0001 ) . The average number of hospitalizations and IV antibiotic courses did not increase over time . TSI treatment was associated with increased weight gain and body mass index . P aeruginosa susceptibility to tobramycin decreased slightly over time , but this was not correlated with clinical response . CONCLUSIONS TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term , intermittent use The major cause of morbidity and mortality in patients with cystic fibrosis ( CF ) is respiratory disease ( Penketh et al. , Thorax 1987 ; 42 : 526 - 532 ) . Recent studies in the USA have shown that intermittent administration of inhaled tobramycin is beneficial to patients with CF who are chronically infected with Pseudomonas aeruginosa ( Ramsey et al. , N Engl J Med 1999 ; 340 : 23 - 30 ; Ramsey et al. , Proceedings of the 12th Annual North American Cystic Fibrosis Conference , 1998 , Montreal , Canada ; Ramsey et al. , Abstract from 23rd European Cystic Fibrosis Conference , 1999 , the Hague , Netherl and s ) . In Europe , the use of nebulised colistin in patients chronically infected with P. aeruginosa is widespread . A recently published study compared the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients . One hundred and fifteen patients were r and omised to receive either TNS or colistin in a multi-centre open-labelled study that assessed change from baseline in FEV(1 ) and sputum P. aeruginosa density . TNS produced a mean 6.7 % improvement in lung function ( P=0.006 ) , whilst there was no significant improvement in the colistin-treated patients . The TNS-treated patients had a significantly greater improvement in lung function than those treated with colistin ( P=0.008 ) . The safety profile of both treatments was good . We conclude that patients treated with TNS for 1 month experience improved lung function compared with patients treated with colistin Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis ( CF ) patients . The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients chronically infected with P. aeruginosa . One-hundred and fifteen patients , aged ≥6 yrs , were r and omised to receive either TNS or colistin , twice daily for 4 weeks . The primary end point was an evaluation of the relative change in lung function from baseline , as measured by forced expiratory volume in one second % predicted . Secondary end points included changes in sputum P. aeruginosa density , tobramycin/colistin minimum inhibitory concentrations and safety assessment s. TNS produced a mean 6.7 % improvement in lung function ( p=0.006 ) , whilst there was no significant improvement in the colistin-treated patients ( mean change 0.37 % ) . Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density , and there was no development of highly resistant strains over the course of the study . The safety profile for both nebulised antibiotics was good . Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa , but colistin did not , in this study of 1-month 's duration . Both treatments reduced the bacterial load OBJECTIVES This r and omized , double-blind , cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis ( CF ) infected with Pseudomonas aeruginosa with and without airway hyperreactivity . DESIGN Of 19 children with CF ( age range , 7 to 16 years ) with mild-to-moderate pulmonary disease , 10 children were at high risk ( HR ) for bronchospasm ( family history of asthma and previous response to bronchodilators ) and 9 children were at low risk ( LR ) for bronchospasm ( no family history of asthma or previous response to bronchodilators ) . Two solutions of tobramycin were administered : ( 1 ) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites ( IV preparation ) ; and ( 2 ) 300 mg in a preservative-free preparation in a 5-mL solution . Following a bronchodilator-free period of 12 h , the patients inhaled either one or the other preparation in r and om order on two different occasions , 2 weeks apart . RESULTS Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1 ) ( DeltaFEV(1 ) ) of 12 + /- 9 % ( mean + /- SD ) for the IV preparation , compared to 4 + /- 5 % for the preservative-free preparation ( p = 0.046 ) . An DeltaFEV(1 ) of > 10 % was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation . For the HR group , the DeltaFEV(1 ) was 17 + /- 13 % for the IV-preparation group , compared to 16 + /- 12 % for the preservative-free group ( p = 0.4 ) . In this group , equal numbers of patients ( 8 of 10 patients ) had an DeltaFEV(1 ) > 10 % after inhaling each preparation . The largest DeltaFEV(1 ) was 44 % ( HR group with the preservative-free preparation that forced the early termination of inhalation ) . CONCLUSIONS Both preparations caused significant bronchoconstriction in the HR group , and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution . Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis ( CF ) , antibiotic therapy generally fails to eradicate the bacterial pathogen . The mucoid bacterial phenotype , high sputum production by the host , and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy . We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection . In a prospect i ve placebo-controlled , double-blind , r and omized multicenter study , 22 CF patients received either 80 mg b.i.d . of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization . Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period . Using life table analysis , the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group ( P < 0.05 , log rank test ) . Lung function parameters and markers of inflammation did not change in either group during treatment . The results of this study suggest that early tobramycin inhalation may prevent and /or delay P. aeruginosa pulmonary infection in CF patients BACKGROUND Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment . This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients ' preference . METHODS Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second ( FEV1 ) of 54 % predicted ( range 24 - 98 ) were studied . They inhaled a nebulised solution of hypertonic , isotonic , and hypotonic colistin over three consecutive days in r and om order in a double blind fashion . Measurements of chest tightness , using a visual analogue scale ( VAS ) , and FEV1 were recorded before and 0 , 15 , 30 , 60 , and 90 minutes following inhalation . The solution preferred by each patient was determined at the end of the three days . RESULTS All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness , with no differences between the solutions . However , the mean ( SE ) time to the maximum fall in FEV1 % predicted was significantly different between the solutions ( hypertonic 7.8 ( 2.1 ) min , isotonic 19.2 ( 5.5 ) min , and hypotonic 34.2 ( 5.9 ) min ) with a mean difference ( 95 % CI ) between hypotonic and hypertonic solutions of 28.04 ( 14.6 to 41.5 ) min , between isotonic and hypertonic solutions of 12.0 ( -0.1 to 24.1 ) min , and between hypotonic and isotonic solutions of 15.6 ( 1.8 to 29.4 ) min . Positive correlations existed for the maximum fall in FEV1 % predicted between the hypertonic and isotonic solutions ( r = 0.62 , p < 0.001 ) and between the hypotonic and isotonic solutions ( r = 0.64 , p < 0.001 ) . There was no correlation between the objective and subjective measurements for any solution . The patients ' preference varied . CONCLUSIONS All tonicities of colistin caused equal symptoms of chest tightness and reduction in pulmonary function . It is recommended that the patient is challenged with nebulised colistin before prescription of the drug and that the challenge is preceded by an inhaled bronchodilator . Most of the patients preferred the isotonic or hypotonic solutions . The isotonic solution reflects a fall in FEV1 representative of all the solutions . The fall in FEV1 to the hypotonic solution occurred over a longer period and may be better tolerated by some patients BACKGROUND AND METHODS We conducted two multicenter , double-blind , placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection . A total of 520 patients ( mean age , 21 years ) were r and omly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks , followed by four weeks with no study drug . Patients received treatment or placebo in three on-off cycles for a total of 24 weeks . The end points included pulmonary function , the density of P. aeruginosa in sputum , and hospitalization . RESULTS The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second ( FEV1 ) of 10 percent at week 20 as compared with week 0 , whereas the patients receiving placebo had a 2 percent decline in FEV1 ( P<0.001 ) . In the tobramycin group , the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units ( CFU ) per gram of expectorated sputum from week 0 to week 20 , as compared with an increase of 0.3 log10 CFU per gram in the placebo group ( P<0.001 ) . The patients in the tobramycin group were 26 percent ( 95 percent confidence interval , 2 to 43 percent ) less likely to be hospitalized than those in the placebo group . Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum . The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group , as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group . CONCLUSIONS In a 24-week study of patients with cystic fibrosis , intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function , decreased the density of P. aeruginosa in sputum , and decreased the risk of hospitalization Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospect i ve double-blind placebo-controlled study of colistin inhalation . Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline . Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group ( 18 versus 11 ) . Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score , maintenance of pulmonary function and inflammatory parameters . We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy OBJECTIVE The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin , supplemented by amikacin inhalation therapy . METHODS Twenty-one patients were r and omly assigned to oral ciprofloxacin alone ( Group I ) and 23 received ciprofloxacin plus inhaled amikacin ( Group II ) . RESULTS Negative sputum cultures were achieved in 34 patients ( 77 % ) at the end of intensive therapy ( 19 Group I and 15 Group II ) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I ( 26 % ) and in 8 of the 15 responders in Group II ( 53 % ) . Resistance to ciprofloxacin was found in 7 of 31 ( 23 % ) sputum isolates at the end of ciprofloxacin therapy . During maintenance therapy , continued improvement in clinical symptoms was observed in 14 patients in both treatment groups ; 6 in each group had further improvements whereas only 4 patients were clinical failures . There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance . Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age . There were no severe or serious adverse events , no signs of quinolone-related arthropathy and no growth impairment . CONCLUSION Ciprofloxacin was efficacious , safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients . These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted The effect of prophylactic antibiotics on bacterial colonization of the respiratory tract and on general progression of cystic fibrosis was studied in a two-year prospect i ve study of 47 mildly to moderately affected patients . One group of patients received inhaled cephaloridine and the other received no inhaled antibiotic ; both groups received cloxacillin orally . Carriage of Haemophilus influenzae was greater in the group not receiving inhaled antibiotic ( 55 % vs 20 % ) . Rates of carriage of Staphylococcus aureus ( 23 % ) . Pseudomonas aeruginosa ( greater than 90 % ) . Pseudomonas cepacia ( 45 % ) , and other organisms were similar in both groups . There were no significant differences between the two groups in incidence of respiratory tract infections or hospital admissions , clinical scores , radiologic scores , or rate of change of pulmonary function . Although continuous antistaphylococcal antibiotic prophylaxis may be successful in suppressing colonization with S. aureus , it may also contribute to the high rates of carriage of Ps . aeruginosa and Ps . cepacia observed in patients with cystic fibrosis Burkholderia cepacia is an aggressive pathogen that colonizes cystic fibrosis ( CF ) patients , causing greatly increased morbidity and mortality . It is resistant to most antibiotics , but sensitive in vitro to a novel agent , taurolidine . This has not previously been used against B. cepacia , nor given in nebulized form . We assessed the effect of nebulized taurolidine on United Kingdom epidemic ( ET12 ) B. cepacia infection in 20 adult CF patients attending our regional adult cystic fibrosis outpatient clinic using a prospect i ve , r and omized , double-blinded placebo-controlled crossover trial . Nebulized taurolidine ( 4 mL 2 % solution ) or saline ( 4 mL 0.9 % solution ) was given twice daily . Each arm lasted 4 weeks , with a 2-week intervening washout period . Sputum B. cepacia colony counts ( primary outcome measure ) , spirometry , and symptoms ( secondary outcome measures ) were assessed . Eighteen patients completed the study . There was no change in B. cepacia colony counts or spirometry , nor symptom scores . We conclude that , although taurolidine is well tolerated in nebulized form , in this study it had no in vivo anti-B. cepacia activity OBJECTIVE Two identical 24-week , double-blind , placebo-controlled trials of tobramycin solution for inhalation ( TOBI [ PathoGenesis Corporation , Seattle , Washington ] ) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States . The aim of the present study was to extrapolate the US trial data to a Canadian setting , using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces . BACKGROUND Cystic fibrosis is a genetic disease in which persistent respiratory infection , usually due to P. aeruginosa infection , is the major cause of morbidity and mortality . METHODS The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results , reduced sputum levels of P. aeruginosa , and result ed in a 26 % reduction in the probability of hospitalization ( 95 % CI , 2%-43 % vs placebo in the clinical trials ) . Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy . To adjust for Canadian pricing , pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries . Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation . RESULTS Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs ( in Canadian dollars ) of $ 4055 in Ontario and $ 4916 in Quebec , which would substantially offset the Canadian acquisition price of $ 8602 for the same 24-week period . CONCLUSIONS Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting , use of TOBI would reduce the use of health care services , particularly hospital days , and lead to substantial savings in direct medical costs that would offset its acquisition price . Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation BACKGROUND Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function , with low systemic toxicity . We conducted a r and omized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections . METHODS Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and r and omly assigned to one of two crossover regimens . Group 1 received 600 mg of aerosolized tobramycin for 28 days , followed by half-strength physiologic saline ( placebo ) for two 28-day period . Group 2 received placebo for 28 days , followed by tobramycin for two 28-day periods . Pulmonary function , the density of P. aeruginosa in sputum , ototoxicity , nephrotoxicity , and the emergence of tobramycin-resistant P. aeruginosa were monitored . RESULTS In the first 28-day period , treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second ( 9.7 percentage points higher than the value for placebo ; P < 0.001 ) , forced vital capacity ( 6.2 percentage points higher than the value for placebo ; P = 0.014 ) , and forced expiratory flow at the midportion of the vital capacity ( 13.0 percentage points higher than the value for placebo ; P < 0.001 ) . A decrease in the density of P. aeruginosa in sputum by a factor of 100 ( P < 0.001 ) was found during all periods of tobramycin administration . Neither ototoxicity nor nephrotoxicity was detected . The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration . CONCLUSIONS The short-term aerosol administration of a high dose of tobramycin in patients with clinical ly stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated The development of drug resistance is a major theoretical concern with the long-term delivery of aerosolized antibiotics via inhalation . A r and omized , placebo-controlled , double-blind study , which compared inhaled tobramycin plus st and ard cystic fibrosis ( CF ) care to placebo plus st and ard CF care , examined the following microbiological parameters : percentage of patients with at least one Pseudomonas aeruginosa ( PA ) strain with a minimal inhibitory concentration ( MIC ) > 16 microg/mL ( ie , the breakpoint for tobramycin resistance delivered by the parenteral route ) ; changes in the levels of the lowest concentration required to inhibit the growth of 50 % of strains tested ( MIC(50 ) ) and 90 % of strains tested ( MIC(90 ) ) ; the percentage of patients with an increase , decrease , or change in the MIC of the most resistant and most prevalent PA strains ; and the percentage of patients in whom the PA strain with the highest MIC also was the most prevalent . During the first 6 months , which included three on-drug and off-drug cycles of 4 weeks ' duration each , the percentage of tobramycin-treated patients with at least one PA isolate and with an MIC > 16 microg/mL was 13 % at baseline , 26 % at 20 weeks , and 23 % at 24 weeks vs 10 % , 17 % , and 8 % , respectively , for placebo-treated patients . No significant change was observed in MIC(50 ) at 20 and 24 weeks . The increase in MIC(90 ) was not statistically significant . At 24 weeks , there was no increase in the percentage of patients in either group in whom the PA strain with the highest MIC became most the prevalent strain . After the third on-drug cycle , 33 % of the tobramycin group showed an increase in the MIC of the strain with the highest MIC . This decreased to 26 % after 1 month off drug therapy . A preliminary analysis of the 12-month and 18-month data showed a decrease in the proportion of resistant PA isolates after each off-drug cycle . This return to susceptibility following an off-drug cycle was not observed at 24 months . The mechanism of resistance in this setting is believed to be increased impermeability to drug . At all time points , pulmonary function improved even in patients with MICs of > or = 128 microg/mL. At 6 months , no increase was seen in the rates of superinfection with tobramycin-resistant , Gram-negative pathogens . Increases in Stenotrophomonas maltophilia were detected in patients after 18 and 24 months of tobramycin therapy and were similar to those rates in patients receiving placebo . These rates may be independent of inhalation therapy Twenty-seven patients with cystic fibrosis and endobronchial colonization with Pseudomonas aeruginosa were r and omly assigned to inhale either 2 mL saline ( 12 patients ) or 80 mg tobramycin solution ( 15 patients ) 3 times daily . One control patient died ; all others completed the study ( mean duration 32 months ) . No significant differences were found between the two groups at enrollment . The treatment group showed no change , while the control group had a significant decline in both pulmonary function and clinical status over the study period . Individually , 11 of 12 patients in the control group showed deterioration , while 9 of 15 in the treatment group with susceptible P. aeruginosa at enrollment acquired resistant organisms . There was no evidence of significant nephro- or ototoxicity . Although inhaled tobramycin appeared to arrest the decline in pulmonary status , further work is required to identify patients most likely to respond STUDY OBJECTIVE To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis ( CF ) using a jet nebulizer delivery system . DESIGN A multicenter , open-label , r and omized , crossover study . SETTING Ten tertiary care , university-affiliated , teaching hospitals in the United States . PATIENTS AND CONTROL SUBJECTS Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age , had a diagnosis of CF , and expectorated daily sputum . No control subjects enrolled . INTERVENTIONS Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in r and om order . Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream ( Medic-Aid ; Sussex , UK ) , and the Pari LC ( Pari Respiratory Equipment ; Richmond , Va ) , with a DeVilbiss Pulmoaide compressor ( DeVilbiss Health Care ; Somerset , Pa ) , both administering 300 mg tobramycin in 5 mL of 1/4 normal saline solution ( NS ) . Patients were also administered 600 mg tobramycin in 30 mL of 1/2 NS with the UltraNeb 99/100 ( DeVilbiss ) . MEASUREMENTS Sputum and serum tobramycin concentration and pulmonary function were monitored . An adequate peak sputum tobramycin concentration was defined as > 128 microg/g sputum at any of three time points ( 10 , 60 , or 120 min ) after completion of treatments . RESULTS The peak tobramycin concentrations in expectorated sputum were 687+/-663 microg/g ( mean+/-SD ) with the Pari LC and 489+/-402 microg/g with the Sidestream . Adequate peak sputum tobramycin concentration was achieved in 93 % of the patients with the Sidestream , and in 87 % of the patients with the Pari LC . Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100 , 1,498+/-1,331 microg/g with 30 % of patients having levels exceeding 2,000 microg/g . Serum tobramycin concentrations were < or = 4 microg/mL for all patients following administration with each nebulizer . CONCLUSIONS Adequately high sputum tobramycin concentrations were documented in sputum in > 85 % of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems , Sidestream and Pari LC . The single tobramycin administration delivered by these two systems is well-tolerated To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable , 26 patients who had never received anti-pseudomonas chemotherapy were r and omly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks , whenever Ps aeruginosa was isolated from routine sputum cultures . During the 27 months of the trial , infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects ( 2 [ 14 % ] vs 7 [ 58 % ] ; p less than 0.05 ) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group ( 49/214 [ 23 % ] vs 64/158 [ 41 % ] ; p = 0.0006 ) . Thus , chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients . Microbiology results from two multicenter , double-blind , placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora , antibiotic susceptibility , and selection of P. aeruginosa isolates with decreased tobramycin susceptibility . Clinical response was examined to determine whether current susceptibility st and ards are applicable to aerosolized administration . Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia , Stenotrophomonas maltophilia , or Alcaligenes xylosoxidans ; however , isolation of C and ida albicans and Aspergillus species did increase . Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group , there was no evidence of selection for the most resistant isolates to become most prevalent . The definition of resistance for parenteral administration does not apply to inhaled tobramycin : too few patients had P. aeruginosa with a tobramycin MIC > /=16 microgram/mL to define a new break point on the basis of clinical response OBJECTIVES Despite the central importance of pulmonary exacerbations ( PExs ) as an outcome measure in cystic fibrosis clinical trials , no st and ardized definition of PEx exists . We conducted a prospect i ve , multicenter study to establish a st and ardized PEx definition and score for use in clinical trials , based on clinical status rather than on treatment decisions . STUDY DESIGN Subjects were 246 patients enrolled in the placebo arm of a r and omized , controlled trial of tobramycin for inhalation . Physician-investigators completed PEx question naires on all subjects at scheduled intervals during the 6-month study , indicating new or worsening symptoms , physical examination findings , and impression of PEx status ( presence or absence and severity ) . Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx . RESULTS We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings ; one also includes change in forced expiratory volume in 1 second over the preceding month . Both scores were sensitive and specific for predicting the presence of a PEx ( sensitivity , 86 % ; specificity , 86 % ) . The scores were vali date d in subjects in the intervention arm of the trial . CONCLUSION We hope that the proposed PEx score might serve as a st and ardized outcome measure for future clinical trials in cystic fibrosis , allowing meaningful comparisons of study results To determine the potential toxicity of prolonged aerosol tobramycin administration , 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks . Prior to , four times during administration and approximately 6 weeks after discontinuation of treatment , we assessed pulmonary function , weight , height , body temperature , eighth cranial nerve function , serum creatinine , blood urea nitrogen , urinary creatinine clearance , plasma iothalamate clearance , urinary beta-2 microglobulin concentration , and Pseudomonas aeruginosa density in sputum . There was no detectable laboratory evidence of nephrotoxicity . Neither a decrease in auditory acuity ( range 250 - 20,000 Hz ) nor vestibular dysfunction was detected . Pulmonary function tests significantly improved during the first month in all subjects ( P less than 0.05 ) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol . Sputum P. aeruginosa density initially decreased from a mean of 10(7 ) cfu/gm to a mean of 10(4 ) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout . Coincident with the reduced bacterial density , a reduction in cough frequency and sputum production , as well as a weight gain was observed . Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration . However , 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin . We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity . Transient emergence of tobramycin resistant P. aeruginosa may occur In a previously published placebo-controlled trial , tobramycin solution for inhalation ( TSI ) was shown to improve lung function and other outcomes in patients with cystic fibrosis ( CF ) . The objectives of the current study were to examine the effects of TSI on global ratings of health-related quality of life ( HRQOL ) by patients ( or their parents ) and physicians blind to group assignment , and to determine whether any perceived benefits persisted over time . The global ratings of HRQOL in 520 patients with CF and chronic Pseudomonas aeruginosa infection were analyzed retrospectively . Patients were r and omly assigned to receive 24 weeks of placebo or treatment with TSI 300 mg b.i.d . , both administered in cycles of 28 days on drug ( or placebo ) followed by 28 days off , for a total of three cycles . After each on-drug cycle , patients or parents , and physicians , were asked to rate whether the patient 's condition was better , unchanged , or worse . There was strong agreement between the paired patient/parent and physician global HRQOL ratings across the three cycles . Regression analyses demonstrated that patients in the TSI group were significantly more likely to report improvements in HRQOL than were patients in the placebo group . This effect was found to be both immediate ( end of on-drug cycle 1 ) and delayed ( end of subsequent on-drug cycles 2 and 3 ) ( P < 0.05 ) . In addition , change in forced expired volume in 1 sec ( FEV(1 ) ) % predicted values was a significant predictor of improvement in HRQOL ratings by patients and parents . After controlling for change in FEV(1 ) % predicted , physician ratings showed significant improvement only at the end of cycle 1 . Finally , controlling for initial lung disease severity , longitudinal growth models revealed that patients on TSI and their physicians reported higher HRQOL ratings than did placebo patients and their physicians across the three cycles ; however , the magnitude of this effect decreased over time . Results of this study provided consistent evidence that TSI was associated with improved global ratings of HRQOL completed by both patients or parents , and physicians . Although these results are promising , they are limited by the use of a single-item rating of health . Future studies of the effects of TSI should utilize a well-vali date d , disease-specific measure of HRQOL Tobramycin nebuliser solution ( TNS ) has been investigated in several clinical trials , including a large , placebo-controlled study that demonstrated efficacy over a 24-week period . The open-label extension phase of this trial enabled observations to be conducted for an additional period of almost 18 months . Patients from both treatment arms ( n=396 ) entered the open-label phase and received up to nine 28-day on , 28-day off cycles of TNS 300 mg by aerosol twice daily ( b.i.d . ) . Mean lung function in patients who had received placebo during the double-blind phase improved during the first three cycles of the open-label treatment . However , lung function in these patients did not recover to the levels seen in those patients who had received TNS throughout the double-blind and open-label phases . In both groups of patients , improvement was maintained during the study . Greater improvements were seen in adolescents compared with older patients . Adverse events were generally uncommon , with a notably lower incidence of fever , anorexia , abdominal pain and vomiting than was observed in the double-blind phase among patients who received placebo , and a generally low incidence of tinnitus . We conclude that long-term TNS administration is safe and effective Eighty-seven patients with cystic fibrosis were admitted to hospital with an acute exacerbation of pulmonary symptoms associated with isolation of Pseudomonas aeruginosa from sputum . The patients were r and omly allocated to receive intravenously administered ceftazidime ( 250 mg/kg/day ) and amikacin ( 33 mg/kg/day ) alone or with inhaled amikacin ( 100 mg twice a day ) . Other aspects of the 2-week treatment were constant . The two therapy groups were comparable in all aspects . At the completion of therapy , the addition of aerosolized amikacin produced temporary eradication of P. aeruginosa in 70 % of the patients , compared with 41 % in the intravenous therapy only group ( P less than 0.02 ) . Suppression of P. aeruginosa in sputum cultures was correlated with the amikacin sputum concentrations . However , both regimens result ed in similar improvements in clinical , radiologic , laboratory , and pulmonary function measurements , and within 4 to 6 weeks most patients were recolonized with P. aeruginosa . There was no serious toxicity or adverse effect . In patients with cystic fibrosis , the addition of aerosol aminoglycoside to systemic antipseudomonal combination therapy is not clinical ly beneficial |
509 | 25,728,564 | There is evidence for the use of narrow-b and UV-B and UV-A1 phototherapy in moderate to severe atopic dermatitis .
Evidence supporting the use of PUVA in atopic dermatitis is scarce and there is little information on the use of phototherapy in childhood . | BACKGROUND Phototherapy is a treatment option for atopic dermatitis recommended by several guidelines .
OBJECTIVE To perform a systematic review of the efficacy of different modalities of phototherapy and photochemotherapy in moderate to severe atopic dermatitis . | UVB phototherapy of atopic dermatitis was investigated in two paired‐comparison studies . In study 1 , 17 patients were treated for 8 weeks with ultraviolet B radiation ( UVB ) on one half of the body and with visible light ( placebo ) on the other . A severity score based on eight clinical variables was determined before , during and after treatment . The total score , pruritus score and overall evaluation score were significantly better on the UVB treated sides than on the placebo treated sides ( P < 0.001 ) . In 13 patients the UVB treated side healed or improved considerably , while the placebo treated side improved considerably in one patient only In a paired-comparison study 30 patients with atopic dermatitis underwent treatment with a combination of UVA and UVB radiation ( UVAB ) on one side of the body and UVB on the other . Treatment was administered three times a week for a maximum of 8 weeks . Each patient was evaluated with respect to eight effect variables . Statistically significant differences in favor of UVAB were observed for all analyzed variables , namely total score ( p = 0.002 ) , pruritus score ( p = 0.04 ) , and overall evaluation score ( p = 0.03 ) . No statistically significant differences in healing rate were seen ; 25 of 30 UVB-treated , and 26 of 30 UVAB-treated , body halves healed or were considerably improved . Patient preference was overwhelmingly in favor of UVAB ; 23 of 24 patients who completed an evaluation form preferred this treatment . Only 1 of 24 preferred UVB BACKGROUND Besides glucocorticosteroids , there is currently no known effective therapy for patients with acute atopic dermatitis . OBJECTIVE The therapeutic effectiveness of high-dose UVA1 irradiation in the management of patients with acute exacerbation of atopic dermatitis was examined . METHODS Patients in the high-dose UVA1 group ( n = 15 ) were irradiated with 130 joules/cm2 UVA1 ; the control group ( n = 10 ) was treated with UVA-UVB therapy in a minimal erythema dose-dependent manner ( total number of treatments 15 ) . RESULTS High-dose UVA1 irradiation was found to induce a significant clinical improvement of atopic dermatitis ( p less than 0.001 ) . In comparison with UVA-UVB therapy , significant differences in favor of high-dose UVA1 were observed ( p less than 0.01 ) . High-dose UVA1 , but not UVA-UVB treatment , significantly reduced the elevated serum level of eosinophil cationic protein in patients with atopic dermatitis ( p less than 0.003 ) . CONCLUSION These studies indicate that high-dose UVA1 irradiation may represent a novel phototherapeutic modality for the treatment of patients with an acute exacerbation of atopic dermatitis Two paired-comparison left-right studies were conducted with patients suffering from atopic dermatitis . In study 1 , 18 patients were treated with low-dose ultraviolet B ( UVB ) radiation on one body-half and with combined UVA and UVB ( UVAB ) on the other 3 times a week for up to 8 weeks . Eight effect variables were recorded . Statistically significant differences in favor of UVAB were seen for 3 variables analyzed , total score , overall evaluation score and pruritus score . The healing score was likewise better with UVAB ; 17 patients achieved healing or considerable improvement as compared with 5 patients with UVB treatment . The result was judged to be better with UVAB in 16 subjects and equal in 2 . In none of the cases did low-dose UVB yield better results . Sixteen patients preferred UVAB to UVB , 2 had no preference , but none preferred low-dose UVB . In study 2 , the arms or legs of 25 patients were treated with UVA and UVAB , respectively , 5 days a week for 3 weeks . UVAB proved to be better when comparing total score and overall evaluation score . No difference in pruritus score was detected . The healing score favored UVAB . Twenty-three patients healed or improved considerably with UVAB as compared with 17 patients with UVA . Better results were achieved with UVAB in 15 patients , with UVA in 4 , and both therapies yielded equal results in 6 cases . Eighteen patients preferred UVAB , 5 UVA and 2 neither . Both UVA and UVAB yielded scores superior to untreated control patches BACKGROUND Narrow-b and ultraviolet B ( UVB ) is an effective treatment for psoriasis , and open studies suggest that this phototherapy might improve atopic eczema . We did a r and omised controlled trial to compare narrow-b and UVB , UVA , and visible light phototherapy as second-line , adjunctive treatments in adult patients with moderate to severe atopic eczema . METHODS Phototherapy was administered twice a week for 12 weeks . 26 patients were r and omly assigned narrow-b and UVB , 24 were assigned UVA , and 23 visible fluorescent light . The primary endpoints were change in total disease activity ( sum of scores at six body sites ) and change in extent of disease after 24 treatments compared with baseline . Data were analysed by the method of summary measures . FINDINGS 13 patients withdrew or were excluded from analysis . Mean reductions in total disease activity over 24 treatments in patients who received narrow-b and UVB and UVA , respectively , were 9.4 points ( 95 % CI 3.6 to 15.2 ) and 4.4 points ( -1.0 to 9.8 ) more than in patients who received visible light . Mean reductions in extent of disease after 24 treatments with narrow-b and UVB and UVA were 6.7 % ( 1.5 to 11.9 ) and -1.0 % ( -5.3 to 3.3 ) compared with visible light . A small proportion of patients developed erythema after phototherapy or had a flare in their eczema sufficient to withdraw from treatment . INTERPRETATION Narrow-b and UVB is an effective adjunctive treatment for moderate to severe atopic eczema , and the treatment is well tolerated by most patients BACKGROUND Data from an uncontrolled trial suggest synchronous balneophototherapy ( sBPT ) , which simulates treatment conditions at the Dead Sea , to be effective in the management of atopic dermatitis ( AD ) . OBJECTIVES The purpose of this prospect i ve r and omized controlled study was to compare the efficacy and safety of sBPT with narrow-b and ( NB ) UVB monotherapy ( PT ) for AD . METHODS In this phase III multicentre trial , 180 patients with moderate-to-severe AD were allocated to two groups in a 1:1 ratio ; group 1 received sBPT consisting of NB UVB treatment and synchronous bathing in 10 % Dead Sea salt solution , group 2 monotherapy with UVB 311 nm . The confirmatory study design consisted of up to 35 treatment sessions . Primary endpoint , analysed on an intention-to-treat-basis ( n=169 ) , was the relative improvement of the severity SCORing of the Atopic Dermatitis Index ( SCORAD ) from baseline to the end of treatment ( 35 sessions or early cure ) . Sample -size calculation aim ed at establishing at least 15 % superiority . RESULTS SCORing of the Atopic Dermatitis Index at baseline was comparable between sBPT ( 61.8±14.1 ) and PT ( 61.5±12.4 ) group . At the end of therapy , a clinical ly relevant and statistically significant difference of 26.2 % could be shown ( P<0.001 ) . Exploratory testing showed statistically significant superiority of sBPT after 6 months . Mild adverse events more frequently occurred in the sBPT group ( n=46 , PT : n=31 ) , whereas more patients withdrew early because of adverse events in the PT group ( n=6 , sBPT : n=2 ) . CONCLUSIONS A clear advantage of sBPT in comparison to PT was proven . Tolerability was comparable ; both treatments showed to be safe BACKGROUND Several studies have demonstrated the efficacy of UVA1 ( 340 - 400 nm ) phototherapy for patients with severe atopic dermatitis . However , the optimum treatment dose has yet to be determined . Although in seminal investigations high UVA1 doses were used , comparable results were reported in recent studies with a medium-dose regimen . OBJECTIVE Our purpose was to compare the efficacy of high-dose with medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis . METHODS Ten adult patients with a median baseline SCORAD score of 67 were enrolled in an investigator-blinded , bilateral comparison study . Treatment was given 5 times weekly over a period of 3 weeks on an outpatient basis . Irradiation was performed by exposing one half of the patient 's body to high-dose UVA1 ( < or = 130 J/cm(2 ) ) , and the contralateral body side received only half that dose . The clinical response was assessed after 5 , 10 , and 15 treatments . After completion of the study , patients were followed up for 6 months to evaluate the duration of clinical improvement . RESULTS All but one patient responded favorably to treatment . High-dose UVA1 led to a decrease of the median SCORAD score by 33.4 % after 1 week , 38.4 % after 2 weeks , and 34.7 % after 3 weeks . The respective values for the medium-dose regimen were 29.7 % , 36.4 % , and 28.2 % . The difference in efficacy between the two dosages remained below the level of significance at all time points . Relapses occurred after a median of 4 weeks . Time of onset and severity of relapse were the same for both doses . CONCLUSION Our data support previous uncontrolled observations that medium-dose UVA1 is comparably as effective as high-dose treatment for patients with severe generalized atopic dermatitis . Irrespective of the dose regimen , follow-up examinations revealed early relapse in the majority of patients BACKGROUND Phototherapy may be effective in atopic dermatitis ( AD ) . Medium-dose ( MD ) ultraviolet ( UV ) A1 was introduced for the treatment of AD . Few immunohistochemical data are available pertaining to phototherapy in AD . Regulatory T cells may play a role in clearing AD . OBJECTIVES We sought to compare the clinical and immunohistochemical effects of narrowb and ( NB ) UVB and MD UVA1 treatment in patients with AD . METHODS Thirteen adult patients with AD were included in this r and omized investigator-blinded half-sided comparison study between NB UVB and MD UVA1 . Disease activity was measured using the Leicester sign score . Skin biopsy specimens were taken before and after phototherapy . Regulatory T cells were stained with the forkhead box protein P3 ( FoxP3 ) . RESULTS NB UVB and MD UVA1 both significantly decreased AD severity ( P < .01 ) and the dermal cellular infiltrate . The percentage of FoxP3(+)CD3(+ ) T cells did not change after NB UVB or MD UVA1 treatment . LIMITATION MD UVA1 therapy was given 3 times per week instead of the preferred regimen of 5 times per week . This was necessary to achieve good blinding of the study . CONCLUSIONS NB UVB and MD UVA1 seem equally effective in the treatment of patients with moderate to severe AD . Neither MD UVA1 nor NB UVB had an effect on the percentage of FoxP3(+)CD3(+ ) T cells Summary In a paired‐comparison study , 21 patients suffering from atopic dermatitis were treated with fluorescent tubes radiating mainly ultraviolet A ( UVA ) on one half of the body and with tubes radiating mainly UVB on the other . Treatment was given three times a week for up to 8 weeks . Eight variables reflecting disease status were recorded and the sum of these comprised the total score . The total score and the overall evaluation score were better with UVA therapy ( p<0·02 and P=0·01 , respectively . No statistically significant difference for the pruritus score was found . The reduction in extent of dermatitis , seen with both therapies , was more pronounced with UVA ( P<0·05 ) . Differences in the healing score were not statistically significant . Treatment with UVA result ed in healing or considerable improvement in 15 patients and 13 patients showed improvement when treated with UBA . A better result was found with UVA in 10 subjects and with UVB in two subjects . Equal results occurred with both UVA and UVB in nine of the patients although most preferred UVA treatment BACKGROUND The results of an open , single-center study suggested that phototherapy with high doses of UVA1 radiation ( UVA1R ; 340 - 400 nm ) is effective for acute , severe exacerbations of atopic dermatitis ( AD ) . OBJECTIVE The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute , severe AD in a r and omized multicenter trial in direct comparison with topical glucocorticoid therapy . METHODS Patients were treated with high-dose UVA1R ( 10 days , 130 J/cm2/day ; n = 20 ) , topically with fluocortolone ( 10 days , 1 x daily ; n = 17 ) , or with UVA-UVB therapy ( 10 days , 1 x daily , minimal erythema dose-dependent ; n = 16 ) . RESULTS With a clinical scoring system , significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed ( p < 0.0001 ) , as compared with UVA-UVB therapy . At day 10 , high-dose UVA1R was superior to fluocortolone ( p < 0.002 ) therapy . Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone , but not UVA-UVB therapy . CONCLUSION This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD Although cyclosporin is effective for the treatment of severe atopic dermatitis , phototherapy is the st and ard second-line treatment for this disease . An open , r and omized , controlled , parallel-group study was conducted to compare the efficacy , influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients . The main endpoints of the study were the number of days in remission and the influence on quality of life . Seventy-two patients were treated , 36 in each group . Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period . At the end of the study no difference between the 2 groups was noted in terms of quality of life . A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment . It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period In patients with severe chronic atopic dermatitis ( AD ) , both photochemotherapy [ psoralen ultraviolet A ( PUVA ) ] and narrow‐b and ( TL‐01 ) UV B phototherapy have been reported to be very effective . As no data exist on the relative therapeutic efficacy of these two regimens , we performed a r and omized investigator‐blinded half‐side comparison study on 12 patients with severe chronic AD . Half‐side irradiation with threshold erythemogenic doses of 8‐methoxypsoralen bath‐PUVA and narrow‐b and UVB was performed three times weekly over a period of 6 weeks . The severity of the disease was assessed separately for the paired halves of the patients ’ bodies by a modified SCORAD score at baseline and after 2 , 4 and 6 weeks of treatment . Ten of the 12 patients completed the trial . All but one showed marked improvement or complete remission with both treatments . The mean baseline SCORAD score decreased by 65·7 % by the bath‐PUVA treatment and by 64·1 % by the narrow‐b and UVB treatment ( P = 0·48 ) . No serious adverse reactions to either of the two regimens were observed . Our data confirm the high efficacy of bath‐PUVA and narrow‐b and UVB phototherapy in the treatment of patients with chronic severe AD . Both regimens appear to be equally effective when administered in equi‐erythemogenic doses A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids , azathioprine , and photochemotherapy . 33 patients took part in a double-blind , placebo-controlled , crossover study to assess the efficacy and safety of cyclosporin ( 5 mg/kg per day ) in adults with severe refractory atopic dermatitis . Treatments were given for eight weeks each with one group ( n = 16 ) receiving placebo followed by cyclosporin and another ( n = 17 ) receiving cyclosporin and then placebo . Disease activity , extent of disease , sleep and itch , topical steroid use , and adverse events were assessed every two weeks . Both extent and activity of dermatitis were significantly improved ( p less than 0.001 ) as were subjective measures of disease . 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo , although no patient required withdrawal from the study . Cyclosporin therapy led to an increase in the mean serum urea , creatinine , and bilirubin concentrations , although only the rise in bilirubin was significant ( p = 0.001 ) . Our results confirm that cyclosporin is a safe and effective short-term treatment for severe , refractory atopic dermatitis BACKGROUND AND OBJECTIVE UVA1 phototherapy is an new effective treatment modality for acute atopic dermatitis ( AD ) . However there is still some controversy about the optimal UVA1 single and cumulative dose . PATIENTS / METHODS We compared in a r and omized , controlled , prospect i ve pilot study the efficacy of a therapy with 15 treatments of a " high dose " ( max . single dose of 130 J/cm2 , max . cumulative dose 1840 J/cm2 ) , " medium dose " ( max . single dose of 65 J/cm2 , max . cumulative dose 975 J/cm2 ) or " low dose " ( max . single dose of 20 J/cm2 , max . cumulative dose 300 J/cm2 ) UVA1 in patients with acutely exacerbated atopic dermatitis ( SCORAD > 30 ) . After determination of the IPD , patients r and omized into one of the three treatment arms . The patients received 15 treatments ( 5 times per week ) without any additional therapy except for topical skin care . RESULTS After 15 treatments the " high dose " and " medium dose " groups showed a statistically significant reduction of the SCORAD . No significant reduction of the SCORAD was observed in the " low dose " group . All three treatment arms displayed no statistically significant changes in the IgE and ECP levels and in the number of eosinophils in the peripheral blood . The UVA1 therapy was well tolerated by all patients . No side effects were observed . CONCLUSIONS This study suggests that both the " high dose " and the " medium dose " regimens are effective in the treatment of patients with acutely exacerbated atopic dermatitis In a r and omized , open , left-right comparison study , 20 patients with atopic dermatitis were treated with UVB . One side of the body received UVB in a conventional regimen with fixed dosage increments , the other side was given UVB dosages according to skin reflectance measurements of skin pigmentation and erythema . Clinical outcome was assessed by SCORAD . The initial , final and cumulative UVB dosages , time to 50 % reduction in SCORAD , and side effects were compared . The initial UVB dosage was somewhat higher in the skin reflectance-guided treatment than in the conventional UVB regimen , although not significantly . There was no difference in the reduction of SCORAD comparing the two treatment options ; however , the final UVB dosage and the cumulative UVB dosages were significantly lower in the optimized regimen . This new technique offers the same therapeutic advantage and security as a dose regimen guided by minimal erythema dose testing . However , measurement of skin pigmentation by skin reflectance is a rapid method , which can easily be operated by nurses BACKGROUND : Atopic dermatitis ( AD ) is a genetically determined pruritic skin disease affecting predominantly young people . The therapy of AD includes mainly corticosteroids ( CS ) , antihistamines and immunosuppressors . CS are known to cause a variety of side effects and attempts have been made to reduce or eliminate their use through alternative methods such as phototherapy ( UVA/UVB , UVA1 , UVB 311 nm ) . In order to optimize therapeutic efficacy the effects of CS and UV radiation are often combined . OBJECTIVE : To evaluate the efficacy of UVA/UVB and UVA/UVB plus topical CS phototherapy of AD and to compare the two regimens with regard to their therapeutic effect , duration of treatment and remissions , cumulative UVA and UVB doses and side effects . METHODS : Thirty‐one patients ( mean age 19 years ) with moderate‐to‐severe forms of AD were enrolled in the study ( mean disease duration of 17.7 years ) . Seventeen patients were treated with UVA/UVB phototherapy ( Group I ) . Fourteen patients received UV irradiation combined with topical CS ( Group II ) . The starting UVA dose was 2–2.5 J/cm2 . The initial UVB dose depended on skin phototype . The procedures were held five times weekly . In order to evaluate therapeutic efficacy , 10 severity criteria and 10 topographic sites were scored at the beginning and at the end of treatment . RESULTS : A statistically significant difference in the severity of the disease was observed before and after phototherapy in both groups ( overall clinical score Group I : t=10.1 , p=0.0001 ; Group II : t=13.9 , p=0.0001 ) . Erythema ( t=12.1 , p<0.0001 ) , excoriations ( t=10.1 , p<0.0001 ) and vesiculation improved most dramatically after UVA/UVB phototherapy . Lichenification ( t=2.5 , p=0.024 ) , xerosis ( t=10.2 , p<0.001 ) and pruritus ( t=13.7 , p<0.0001 ) also diminished significantly . The combination regimen had a similar effect on different severity criteria , but initial signs of improvement appeared earlier . Side effects observed during phototherapy included erythema , burning , skin xerosis and sweating . No statistically significant difference was established between the therapeutic efficacy of the two treatment modalities ( t=0.2 , p=0.904 ) , but the addition of CS reduced the duration of treatment ( number of procedures : t=2.5 , p=0.02 ) and total UVB dose ( t=2.3 , p=0.03 ) . There was no significant difference between the duration of remissions ( t=0.9 , p=0.39 ) and frequency of side effects in the two groups of patients . CONCLUSION : Both UVA/UVB monotherapy and UVA/UVB + topical CS lead to significant clinical improvement in patients with AD , but the addition of CS reduces the total UVB dose and duration of treatment without influencing the duration of remissions and frequency of side effects BACKGROUND Recently , conventional high-dose UVA1 phototherapy ( 340 - 400 nm ) has been shown to be more effective than combined UVA-UVB therapy in the treatment of severe atopic dermatitis ( AD ) . However , there are limitations of this treatment , such as intense sweating caused by the immense heat load during therapy and the high cumulative UVA1 doses that are required . For this reason , lavish UVA1 equipment was developed containing an advanced filtering and cooling system result ing in almost complete absence of heat load and sweating during therapy . OBJECTIVE In this study we compared the monotherapeutic efficacy of conventional medium-dose UVA1 , medium-dose UVA1 cold-light , and combined UVA-UVB phototherapy in the treatment of severe AD . METHOD The study involved 120 patients with severe AD . Fifty patients each received conventional UVA1 or UVA1 cold-light phototherapy ( 15 days , 50 J/cm(2)/day ) , and 20 patients were treated with combined UVA-UVB ( 15 days , minimal erythema dose dependent ) . Severity of AD was scored by means of the SCORAD score , and clinical improvement was additionally monitored by serologic cytokine markers . RESULTS Six ( 12 % ) of 50 patients treated with UVA1 , 2 ( 4 % ) of 50 patients treated with UVA1 cold-light therapy , and 4 ( 20 % ) of 20 patients treated with combined UVA-UVB therapy discontinued treatment prematurely because of an unsatisfactory clinical outcome or adverse reactions . Skin status improved or even cleared completely in 77.3 % of the patients treated for 3 weeks with conventional UVA1 therapy and in 85.4 % of the patients treated for 3 weeks with UVA1 cold-light therapy , result ing in a significant decrease in the SCORAD score in both UVA1 groups ( P < .05 each ) . In the group treated with combined UVA-UVB , the SCORAD score also decreased but significantly less than in both groups treated with UVA1 photo-therapy ( P < .05 each ) . At follow-up after 4 weeks , the patients treated with UVA1 displayed a more prolonged therapeutic benefit than the patients treated with UVA-UVB therapy . Plasma levels of soluble interleukin 2 receptors and soluble interleukin 4 receptors significantly decreased under both UVA1 and UVA1 cold-light phototherapy but not under combined UVA-UVB phototherapy . CONCLUSION Our study demonstrates that medium-dose UVA1 cold-light phototherapy displays advantages compared with conventional UVA1 phototherapy caused by the almost complete absence of heat load and intense sweating and is more effective than UVA-UVB phototherapy in the treatment of severe AD BACKGROUND Atopic dermatitis ( AD ) is a chronic skin disease result ing in a profound deterioration in quality of life . The FSL ® is a newly developed phototherapy device generating full-spectrum light ( FSL ) with a continuous wavelength ( 320 - 5000 nm ) . This study aim ed to evaluate the efficacy and safety of FSL ® phototherapy in AD . METHODS We enrolled 38 patients with moderate to severe AD in this open , r and omized , controlled , prospect i ve study . In the FSL-irradiated group ( 20 patients ) , irradiation was conducted twice per week for 4 consecutive weeks . In the control group ( 18 patients ) , only emollient application was allowed . SCORing Atopic Dermatis ( SCORAD ) values were obtained at baseline , week 4 and 8 . Patients were asked to give subjective assessment s of improvement and laboratory tests including serum eosinophil counts , ECP levels , IgE levels and 22 cytokine levels were performed . RESULTS In the FSL-irradiated group , the mean SCORAD value decreased significantly after 4 weeks of phototherapy and remained reduced for a further 4 weeks after the cessation of treatment . In the control group , the mean SCORAD value did not change significantly over the study period . Patients ' subjective assessment s indicated good to excellent responses in 75 % of the FSL-irradiated group , by contrast with 50 % of the control group . The mean values for serum eosinophil counts , IL-4 and IL-5 levels decreased significantly after FLS phototherapy . No serious adverse effects were reported . CONCLUSIONS In this study , we showed that FSL ® phototherapy can be an effective and safe treatment option in AD |
510 | 25,732,419 | None of the biomarkers reliably distinguished between IBS and healthy controls .
Individual analysis of ESR and lactoferrin had little clinical utility .
Conclusion : CRP and calprotectin of ≤0.5 or 40 , respectively , essentially excludes IBD in patients with IBS symptoms .
The addition of CRP and calprotectin to symptom-based criteria may improve the confident diagnosis of IBS | Objectives : Irritable bowel syndrome ( IBS ) is viewed as a diagnosis of exclusion by most providers .
The aim of our study was to perform a systematic review and meta- analysis to evaluate the utility of C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , fecal calprotectin , and fecal lactoferrin to distinguish between patients with IBS and inflammatory bowel disease ( IBD ) and healthy controls ( HCs ) . | Background : The correlation between noninvasive markers with endoscopic activity according to the modified Baron Index in patients with ulcerative colitis ( UC ) is unknown . We aim ed to evaluate the correlation between endoscopic activity and fecal calprotectin ( FC ) , C-reactive protein ( CRP ) , hemoglobin , platelets , blood leukocytes , and the Lichtiger Index ( clinical score ) . Methods : UC patients undergoing complete colonoscopy were prospect ively enrolled and scored clinical ly and endoscopically . Sample s from feces and blood were analyzed in UC patients and controls . Results : We enrolled 228 UC patients and 52 healthy controls . Endoscopic disease activity correlated best with FC ( Spearman 's rank correlation coefficient r = 0.821 ) , followed by the Lichtiger Index ( r = 0.682 ) , CRP ( r = 0.556 ) , platelets ( r = 0.488 ) , blood leukocytes ( r = 0.401 ) , and hemoglobin ( r = −0.388 ) . FC was the only marker that could discriminate between different grade s of endoscopic activity ( grade 0 , 16 [ 10–30 ] & mgr;g/g ; grade 1 , 35 [ 25–48 ] & mgr;g/g ; grade 2 , 102 [ 44–159 ] & mgr;g/g ; grade 3 , 235 [ 176–319 ] & mgr;g/g ; grade 4 , 611 [ 406–868 ] & mgr;g/g ; P < 0.001 for discriminating the different grade s ) . FC with a cutoff of 57 & mgr;g/g had a sensitivity of 91 % and a specificity of 90 % to detect endoscopically active disease ( modified Baron Index ≥2 ) . Conclusions : FC correlated better with endoscopic disease activity than clinical activity , CRP , platelets , hemoglobin , and blood leukocytes . The strong correlation with endoscopic disease activity suggests that FC represents a useful biomarker for noninvasive monitoring of disease activity in UC patients OBJECTIVES : Studies evaluating the correlation between the widely used Simple Endoscopic Score for Crohn 's disease ( SES-CD ) and noninvasive markers are scarce . The aim of this study was to evaluate the correlation between the SES-CD and fecal calprotectin , C-reactive protein ( CRP ) , blood leukocytes , and the Crohn 's disease activity index ( CDAI ) . METHODS : Crohn 's disease patients undergoing complete ileocolonoscopy were prospect ively enrolled and scored independently according to the SES-CD and the CDAI . SES-CD was defined as follows : inactive 0–3 ; mild 4–10 ; moderate 11–19 ; and high ≥20 . RESULTS : Values in CD patients ( n=140 ileocolonoscopies ) compared with controls ( n=43 ) are as follows : calprotectin , 334±322 vs. 18±5 μg/g ; CRP , 26±29 vs. 3±2 mg/l ; and blood leukocytes , 9.1±3.4 vs. 5.4±1.9 g/l ( all P<0.001 ) . The SES-CD correlated closest with calprotectin ( Spearman 's rank correlation coefficient r=0.75 ) , followed by CRP ( r=0.53 ) , blood leukocytes ( r=0.42 ) , and the CDAI ( r=0.38 ) . Calprotectin was the only marker that could discriminate inactive endoscopic disease from mild activity ( 104±138 vs. 231±244 μg/g , P<0.001 ) , mild from moderate activity ( 231±244 vs. 395±256 μg/g , P=0.008 ) , and moderate from high activity ( 395±256 vs. 718±320 μg/g , P<0.001 ) . The overall accuracy for the detection of endoscopically active disease was 87 % for calprotectin ( cutoff 70 μg/g ) , 66 % for elevated CRP , 54 % for blood leukocytosis , and 40 % for the CDAI ≥150 . CONCLUSIONS : Fecal calprotectin correlated closest with SES-CD , followed by CRP , blood leukocytes , and the CDAI . Furthermore , fecal calprotectin was the only marker that reliably discriminated inactive from mild , moderate , and highly active disease , which underlines its usefulness for activity monitoring OBJECTIVES : There are limited data on the yield of colonoscopy in patients with irritable bowel syndrome ( IBS ) . This study compared the prevalence of structural colonic lesions in patients with suspected non-constipation-predominant IBS and healthy volunteers . We also determined the yield of rectosigmoid biopsies in patients with suspected IBS . METHODS : This was a prospect i ve , case – control study conducted at three US sites . Patients with suspected non-constipation-predominant IBS ( Rome II ) underwent colonoscopy with rectosigmoid biopsies . Healthy persons undergoing colonoscopy for colorectal cancer screening or polyp surveillance comprised the control group . Abnormalities identified at colonoscopy were compared between suspected IBS and control groups . RESULTS : In all , 466 suspected IBS patients and 451 controls were enrolled . Suspected IBS patients were significantly younger ( P<0.0001 ) and more frequently female ( P<0.0001 ) than controls . The most common lesions in suspected IBS patients were hemorrhoids ( 18.2 % ) , polyps ( 14.6 % ) , and diverticulosis ( 8.8 % ) . Suspected IBS patients had a lower prevalence of adenomas ( 7.7 % vs. 26.1 % , P<0.0001 ) and diverticulosis ( 8.8 % vs. 21.3 % , P<0.0001 ) and higher prevalence of mucosal erythema or ulceration ( 4.9 % vs. 1.8 % , P<0.01 ) compared with controls . Logistic regression found the between-group differences in adenoma prevalence to be robust after correction for demographic factors . The overall prevalence of microscopic colitis in suspected IBS patients was 1.5 % ( 7/466 ) and 2.3 % ( 4/171 ) in those ≥45 years of age . CONCLUSIONS : The prevalence of structural abnormalities of the colon is no higher in suspected non-constipation IBS patients than in healthy controls . Microscopic colitis can be identified in a small proportion of persons with IBS symptoms Background : Symptoms of inflammatory bowel disease ( IBD ) and irritable bowel syndrome ( IBS ) can overlap . We aim ed to determine the accuracy of fecal markers , C‐reactive protein ( CRP ) , blood leukocytes , and antibody panels for discriminating IBD from IBS and to define a “ best test . ” Methods : We prospect ively included 64 patients with IBD ( 36 Crohn 's disease [ CD ] , 28 ulcerative colitis [ UC ] ) , 30 with IBS , and 42 healthy controls . Besides CRP and blood leukocytes , blinded fecal sample s were measured for calprotectin ( PhiCal Test , enzyme‐linked immunosorbent assay [ ELISA ] ) , lactoferrin ( IBD‐SCAN , ELISA ) , Hexagon‐OBTI ( immunochromatographic test for detection of human hemoglobin ) , and LEUKO‐TEST ( lactoferrin latex‐agglutination test ) . Blinded serum sample s were measured for the antibodies ASCA ( ELISA ) and pANCA ( immunofluorescence ) . Results : Overall accuracy of tests for discriminating IBD from IBS : IBD‐SCAN 90 % , PhiCal Test 89 % , LEUKO‐TEST 78 % , Hexagon‐OBTI 74 % , CRP 73 % , blood leukocytes 63 % , CD antibodies ( ASCA+/pANCA− or ASCA+/pANCA+ ) 55 % , UC antibodies ( pANCA+/ASCA− ) 49 % . ASCA and pANCA had an accuracy of 78 % for detecting CD and 75 % for detecting UC , respectively . The overall accuracy of IBD‐SCAN and PhiCal Test combined with ASCA/pANCA for discriminating IBD from IBS was 92 % and 91 % , respectively . Conclusions : The PhiCal Test and IBD‐SCAN are highly accurate for discriminating IBD from IBS . There is only marginal additional diagnostic accuracy when the PhiCal Test and IBD‐SCAN are combined with ASCA and pANCA . ASCA and pANCA have a high specificity for IBD Backgound : Patients being investigated for symptoms of abdominal pain , diarrhoea and or weight loss often undergo small bowel radiology as part of their diagnostic workup mainly to exclude inflammatory bowel disease Prospect i ve measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn 's disease and fifty with ulcerative colitis . The results were related to clinical assessment of disease activity . C-reactive protein levels were raised in both groups but were significantly higher in Crohn 's disease than ulcerative colitis for all categories of disease severity : with mild disease the median and range of C-reactive protein concentration were 4 , 0 - 65 mg/l in Crohn 's disease v. 0 , 0 - 15 mg/l in ulcerative colitis , P less than 0.01 ; in moderate disease the values were 15 , 1 - 100 mg/l v. 3 , 0 - 29 mg/l respectively , P less than 0.05 and in cases of severe disease , 85 , 15 - 183 mg/l v. 12 , 2 - 33 mg/l respectively , P less than 0.001 . Erythrocyte sedimentation rate was also higher in Crohn 's disease but did not closely reflect disease activity in individual patients . C-reactive protein levels corresponded closely with clinical and pathological indices of relapse , remission and response to therapy in patients with Crohn 's disease . The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity , which may be useful in the assessment , management and study of Crohn 's disease BACKGROUND AND AIMS Assessing the presence and degree of intestinal inflammation objective ly , simply , and reliably is a significant problem in gastroenterology . We assessed faecal excretion of calprotectin , a stable neutrophil specific marker , as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn 's disease and those with irritable bowel syndrome . METHODS The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn 's disease ( 35 studies ) by comparing faecal excretions and concentrations using four day faecal excretion of111indium white cells . A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn 's disease ( n=116 ) . A prospect i ve study assessed the value of faecal calprotectin in discriminating between patients with Crohn 's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic . RESULTS Four day faecal excretion of 111indium ( median 8.7 % ; 95 % confidence interval ( CI ) 7–17 % ; normal < 1.0 % ) correlated significantly ( p<0.0001 ) with daily ( median ranged from 39 to 47 mg ; normal <3 mg ; r=0.76–0.82 ) and four day faecal calprotectin excretion ( median 101 mg ; 95 % CI 45–168 mg ; normal < 11 mg ; r=0.80 ) and single stool calprotectin concentrations ( median 118 mg/l ; 95 % CI 36–175 mg/l ; normal < 10 mg/l ; r=0.70 ) in patients with Crohn 's disease . The cross sectional study showed a sensitivity of 96 % for calprotectin in discriminating between normal subjects ( 2 mg/l ; 95 % CI 2–3 mg/l ) and those with Crohn 's disease ( 91 mg/l ; 95 % CI 59–105 mg/l ) . With a cut off point of 30 mg/l faecal calprotectin has 100 % sensitivity and 97 % specificity in discriminating between active Crohn 's disease and irritable bowel syndrome . CONCLUSION The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn 's disease and irritable bowel syndrome Purpose This study was design ed to evaluate the accuracy of four different fecal markers in discriminating between irritable bowel syndrome , inflammatory bowel disease , and other forms of colitis and to examine the feasibility of collecting fecal sample s in out patients . Methods We prospect ively included 20 patients with irritable bowel syndrome , 36 with inflammatory bowel disease ( 24 Crohn ’s disease , 12 ulcerative colitis ) , and 18 with other forms of colitis ( 8 infectious colitis , 5 ischemic colitis , 5 medication-induced colitis ) . Diagnosis was established by clinical , laboratory , and endoscopic workup . Blinded fecal sample s were measured for calprotectin ( PhiCal ™ -Test , ELISA ) , lactoferrin ( IBD-SCAN ™ , ELISA ) , Hexagon OBTI ( immunochromatographic test for detection of human hemoglobin ) , and LEUKO-TEST ( lactoferrin latex-agglutination test ) . Results Overall accuracy for discriminating irritable bowel syndrome from inflammatory bowel disease or other forms of colitis was recorded , respectively : IBD-SCAN ™ 91/100 percent , PhiCal ™ -Test 89/100 percent , LEUKO-TEST 83/89 percent , Hexagon OBTI 77/84 percent , C-reactive protein 71/79 percent , and blood leukocytes 63/68 percent . Differentiation of inflammatory bowel disease from other forms of colitis with fecal markers was as follows : range of overall accuracy from 43 to 50 percent . Overall accuracy ( in percent ) for discrimination of irritable bowel syndrome from patients with Crohn ’s disease in remission ( CDAI<150 ) was : IBD-SCAN ™ 90 , PhiCal ™ -Test 90 , LEUKO-TEST 85 , Hexagon OBTI 77 . Calprotectin and lactoferrin were significantly elevated in patients with Crohn ’s disease with CDAI>150 compared with those in remission . Fecal sampling feasibility in out patients was high ( acceptance rate 95 percent ) . Conclusions IBD-SCAN ™ and PhiCal ™ -Test have the best overall accuracy for detection of colitis , followed by LEUKO-TEST , Hexagon OBTI , C-reactive protein , and blood leukocytes . Accuracy of fecal markers is high even in patients with Crohn ’s disease in remission . Fecal sampling feasibility was high in out patients . Because fecal markers are unspecific , endoscopic workup remains crucial to determine the underlying cause of colitis |
511 | 19,219,920 | BCs have very limited utility in immunocompetent patients hospitalized with CAP . | BACKGROUND Obtaining blood cultures ( BCs ) for patients hospitalized with community-acquired-pneumonia ( CAP ) has been recommended by experts and used as a measure of quality of care .
However , BCs are infrequently positive in these patients and their effect on clinical management has been question ed .
PURPOSE We performed a systematic review of the literature to determine the impact of BCs on clinical management in CAP requiring hospitalization and thus its appropriateness as a quality measure . | 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 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 BACKGROUND Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide , and strains with resistance to cephalosporin are being reported . The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial . METHODS To examine the effect of resistance to penicillin and cephalosporin on mortality , we conducted a 10-year , prospect i ve study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia . RESULTS Among the 504 patients , 145 ( 29 percent ) had penicillin-resistant strains of S. pneumoniae ( minimal inhibitory concentration [ MIC ] of penicillin G , 0.12 to 4.0 micrograms per milliliter ) , and 31 patients ( 6 percent ) had cephalosporin-resistant strains ( MIC of ceftriaxone or cefotaxime , 1.0 to 4.0 micrograms per milliliter ) . Mortality was 38 percent in patients with penicillin-resistant strains , as compared with 24 percent in patients with penicillin-sensitive strains ( P = 0.001 ) . However , after the exclusion of patients with polymicrobial pneumonia and adjustment for other predictors of mortality , the odds ratio for mortality in patients with penicillin-resistant strains was 1.0 ( 95 percent confidence interval , 0.5 to 1.9 ; P = 0.84 ) . Among patients treated with penicillin G or ampicillin , the mortality was 25 percent in the 24 with penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive strains ( P = 0.51 ) . Among patients treated with ceftriaxone or cefotaxime , the mortality was 22 percent in the 59 with penicillin-resistant strains and 25 percent in the 127 with penicillin-sensitive strains ( P = 0.64 ) The frequency of resistance to cephalosporin increased from 2 percent in 1984 - 1988 to 9 percent in 1989 - 1993 ( P = 0.002 ) . Mortality was 26 percent in patients with cephalosporin-resistant S. pneumoniae and 28 percent in patients with susceptible organisms ( P = 0.89 ) . Among patients treated with ceftriaxone or cefotaxime , mortality was 22 percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168 with cephalosporin-sensitive organisms ( P = 0.64 ) . CONCLUSIONS Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia . Hence , these antibiotics remain the therapy of choice for this disease 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 BACKGROUND Since the last British study of the microbial aetiology of community acquired pneumonia ( CAP ) about 20 years ago , new organisms have been identified ( for example , Chlamydia pneumoniae ) , new antibiotics introduced , and fresh advances made in microbiological techniques . Pathogens implicated in CAP in adults admitted to hospital in the UK using modern and traditional microbiological investigations are described . METHODS Adults aged 16 years and over admitted to a teaching hospital with CAP over a 12 month period from 4 October 1998 were prospect ively studied . Sample s of blood , sputum , and urine were collected for microbiological testing by st and ard culture techniques and new serological and urine antigen detection methods . RESULTS Of 309 patients admitted with CAP , 267 fulfilled the study criteria ; 135 ( 50.6 % ) were men and the mean ( SD ) age was 65.4 ( 19.6 ) years . Aetiological agents were identified from 199 ( 75 % ) patients ( one pathogen in 124 ( 46 % ) , two in 53 ( 20 % ) , and three or more in 22 ( 8 % ) ) : Streptococcus pneumoniae 129 ( 48 % ) , influenza A virus 50 ( 19 % ) , Chlamydia pneumoniae 35 ( 13 % ) , Haemophilus influenzae 20 ( 7 % ) , Mycoplasma pneumoniae 9 ( 3 % ) , Legionella pneumophilia 9 ( 3 % ) , other Chlamydiaspp 7 ( 2 % ) , Moraxella catarrhalis 5 ( 2 % ) , Coxiella burnetii 2 ( 0.7 % ) , others 8 ( 3 % ) . Atypical pathogens were less common in patients aged 75 years and over than in younger patients ( 16 % v27 % ; OR 0.5 , 95 % CI 0.3 to 0.9 ) . The 30 day mortality was 14.9 % . Mortality risk could be stratified by the presence of four “ core ” adverse features . Three of 60 patients ( 5 % ) infected with an atypical pathogen died . CONCLUSION S pneumoniae remains the most important pathogen to cover by initial antibiotic therapy in adults of all ages admitted to hospital with CAP . Atypical pathogens are more common in younger patients . They should also be covered in all patients with severe pneumonia and younger patients with non-severe infection BACKGROUND Prompt antibiotic administration , oxygenation measurement , and blood cultures are generally considered markers of high- quality care in the inpatient management of community-acquired pneumonia ( CAP ) . However , few studies have examined the relationship between prompt achievement of process-of-care markers and outcomes for patients with CAP . We examined whether antibiotic administration within 8 hours of hospital arrival , a blood culture within 24 hours , an oxygenation measurement within 24 hours , or performing blood cultures before giving antibiotics was associated with the following : ( 1 ) reaching clinical stability within 48 hours of hospital admission , ( 2 ) a decreased length of hospital stay , or ( 3 ) fewer inpatient deaths . METHODS A retrospective medical record review identified 1062 eligible patients discharged from the hospital with a diagnosis of CAP between December 1 , 1997 , and February 28 , 1998 , among 38 US academic hospitals . We assessed the independent relationship between each process marker and the 3 clinical outcomes , controlling for the Pneumonia Severity Index on admission . We also examined the relationship of pneumonia severity on admission to process marker achievement and clinical outcomes . RESULTS Overall , there was no consistent or statistically significant relationship between achieving process markers and better clinical outcomes ( P>.40 for all ) . We did observe that performing blood cultures within 24 hours was related to not achieving clinical stability within 48 hours ( odds ratio , 1.62 ; 95 % confidence interval , 1.13 - 2.33 ) . However , this finding likely reflects residual confounding by severity of illness , since increasing pneumonia severity on admission was associated with blood culture performance ( P = .009 ) and with shorter times to antibiotic administration ( P = .04 ) . CONCLUSIONS Achieving process-of-care markers was not associated with improved outcomes , but was related to the severity of pneumonia as assessed on admission . Our results highlight the difficulty in demonstrating a link between process-of-care markers and outcomes in observational studies of CAP . R and omized studies are needed to objective ly evaluate the impact of process-of-care markers on CAP outcomes To assess the association between inclusion of a macrolide in a beta-lactam-based empirical antibiotic regimen and mortality among patients with bacteremic pneumococcal pneumonia , 10 years of data from a data base were analyzed . The total available set of putative prognostic factors was subjected to stepwise logistic regression , with in-hospital death as the dependent variable . Of the 409 patients analyzed , 238 ( 58 % ) received a beta-lactam plus a macrolide and 171 ( 42 % ) received a beta-lactam without a macrolide . Multivariate analysis revealed 4 variables to be independently associated with death : shock ( P<.0001 ) , age of > or=65 years ( P=.02 ) , infections with pathogens that have resistance to both penicillin and erythromycin ( P=.04 ) , and no inclusion of a macrolide in the initial antibiotic regimen ( P=.03 ) . For patients with bacteremic pneumococcal pneumonia , not adding a macrolide to a beta-lactam-based initial antibiotic regimen is an independent predictor of in-hospital mortality . However , only a r and omized study can definitively determine whether this association is due to a real effect of macrolides The aim of the study was to determine the incidence of and risk factors for drug resistance of Streptococcus pneumoniae , and its impact on the outcome among hospitalized patients of pneumococcal pneumonia acquired in the community . Consecutive patients with culture-proven pneumococcal pneumonia were prospect ively studied with regard to the incidence of pneumococcal drug resistance , potential risk factors , and in-hospital outcome variables . A total of 101 patients were studied . Drug resistance to penicillin , cephalosporin , or a macrolide drug was found in pneumococci from 52 of the 101 ( 52 % ) patients ; 49 % of these isolates were resistant to penicillin ( 16 % intermediate resistance , 33 % high resistance ) , 31 % to cephalosporin ( 22 % intermediate and 9 % high resistance ) , and 27 % to a macrolide drug . In immunocompetent patients , age > 65 yr was significantly associated with resistance to cephalosporin ( odds ratio [ OR ] : 5.0 ; 95 % confidence interval [ CI ] : 1.3 to 18.8 , p = 0 . 01 ) , and with the presence of > 2 comorbidities with resistance to penicillin ( OR : 4.7 ; 95 % CI : 1.2 to 19.1 ; p < 0.05 ) . In immunosuppressed patients , bacteremia was inversely associated with resistance to penicillin and cephalosporin ( OR : 0.04 ; 95 % CI : 0.003 to 0.45 ; p < 0.005 ; and OR : 0.46 ; 95 % CI : 0.23 to 0.93 ; p < 0.05 , respectively ) . Length of hospital stay , severity of pneumonia , and complications were not significantly affected by drug resistance . Mortality was 15 % in patients with any drug resistance , as compared with 6 % in those without resistance . However , any drug resistance was not significantly associated with death ( relative risk [ RR ] : 2 . 5 ; 95 % CI : 0.7 to 8.9 ; p = 0.14 ) . Moreover , attributable mortality in the presence of discordant antimicrobial treatment was 12 % , as compared with 10 % ( RR : 1.2 ; 95 % CI : 0.3 to 5.3 ; p = 0.67 ) in the absence of such treatment . We conclude that the incidence of drug-resistant pneumococci was high . Risk factors for drug resistance included advanced age , comorbidity , and ( inversely ) bacteremia . Outcome was not significantly affected by drug resistance PURPOSE To evaluate the clinical relevance of cephalosporin ( ceftriaxone/cefotaxime ) resistance among patients with nonmeningeal systemic pneumococcal infection . SUBJECTS AND METHODS From January 1994 to October 2000 , we prospect ively studied 522 episodes of nonmeningeal systemic pneumococcal infections ( 448 pneumonias ) in 499 adults who were treated according to hospital guidelines . In vitro antibiotic susceptibility , as the minimum inhibitory concentration ( MIC ) , was determined by microdilution method . The MIC methods and breakpoints ( cutoffs ) were established by the National Committee for Clinical Laboratory St and ards . RESULTS Of the 522 pneumococcal strains , 413 strains ( 79 % ) were susceptible to ceftriaxone/cefotaxime , MIC < or = 0.5 microg/mL ; 79 ( 15 % ) were intermediate , MIC = 1 microg/mL ; and 30 ( 6 % ) were resistant , MIC = 2 microg/mL. After adjusting for several variables , including pneumococcal serogroups/serotypes , infections due to nonsusceptible ( intermediate and resistant ) pneumococcal strains were independently associated with prior antibiotic therapy , with an odds ratio of 5.9 ( 95 % confidence interval : 2.6 to 13.6 ) . Thirty-day mortality among the 185 patients who were treated with ceftriaxone ( 1 g/d ) or cefotaxime ( 1.5 g every 8 hours ) did not differ by cephalosporin susceptibility : 18 % ( 26/148 ) among those with susceptible organisms , 13 % ( 3/24 ) with intermediate organisms , and 15 % ( 2/13 ) in resistant cases ( P = 0.81 ) . CONCLUSION Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or = 2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints ( cutoffs ) for nonmeningeal pneumococcal infections We performed a prospect i ve , international , observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae . Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin ( minimum inhibitory concentration [ MIC ] , 0.12 - 1 microg/mL ) , and 9.6 % of isolates were resistant ( MIC , > or=2 microg/mL ) . Age , severity of illness , and underlying disease with immunosuppression were significantly associated with mortality ; penicillin resistance was not a risk factor for mortality . The impact of concordant antibiotic therapy ( i.e. , receipt of a single antibiotic with in vitro activity against S. pneumoniae ) versus discordant therapy ( inactive in vitro ) on mortality was assessed at 14 days . Discordant therapy with penicillins , cefotaxime , and ceftriaxone ( but not cefuroxime ) did not result in a higher mortality rate . Similarly , time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy . beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid , regardless of in vitro susceptibility , as determined by current NCCLS breakpoints It has been previously shown that antibiotics given before hospitalization significantly reduce the proportion of positive blood cultures in community-acquired pneumonia ( CAP ) . The aim of this prospect i ve study was to compare the utility and cost- benefits of blood cultures in patients , hospitalized for moderate CAP , who had or had not received antibiotic therapy prior to admission . During 1 year , 53 patients were included and separated into two groups : group 1 patients had not received antibiotic treatment prior to admission ( n = 30 ) , whereas group 2 patients had been treated with antibiotics ( n = 23 ) . Within the first 48 hours , a set of blood cultures was collected if the body temperature was higher than 38.5 degrees C or in the case of shaking chills . A total of 136 blood cultures was collected ; 74 in group 1 and 62 in group 2 . Bacteraemia was significantly more frequent in group 1 than in group 2 , 5/30 patients vs. 0/23 , respectively ( P < 0.05 ) . The cost of negative blood cultures was valued at 13,939.2 FF in group 1 and 13,164.8 FF in group 2 , respectively 464.6 + /- 244.3 FF and 569.3 + /- 233.4 FF per patient ( n.s . ) . Moreover , blood cultures were the method of diagnosis in only one of the five patients with bacteraemia and in no case did a positive blood-culture result influence the initial therapeutic regime . Thus , our results suggest a reduced clinical utility and cost-benefit of blood cultures in patients hospitalized for moderate CAP who have received an antibiotic treatment prior to admission 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 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 STUDY OBJECTIVE To determine the influence of blood culture and susceptibility results and antimicrobial allergy history on fluoroquinolone use in the treatment of community-acquired pneumonia . DESIGN Retrospective analysis of medical records . SETTING Centers for Medicare and Medicaid Services , Seattle , Washington . PATIENTS A total of 10,275 Medicare beneficiaries hospitalized with the diagnosis of pneumonia received antimicrobial treatment within 24 hours of admission . Of these patients , 288 had blood cultures positive for pneumococcus and were matched one-to-one with patients with negative blood and sputum cultures . MEASUREMENTS AND MAIN RESULTS Antimicrobial use at the beginning and end of hospitalization , culture and susceptibility results , and patient allergies were recorded retrospectively and compared between two matched groups : patients with blood cultures positive for Streptococcus pneumoniae and those whose blood and sputum cultures were negative . Neither culture and susceptibility results nor allergy history affected the rate of fluoroquinolone use . Despite infection due to penicillin-susceptible pneumococci and no penicillin allergy , patients received therapy with fluoroquinolones ( 26.7 % ) as frequently as those with culture-negative pneumonia ( 34.9 % ; p=0.401 ) . CONCLUSION Fluoroquinolones are prescribed despite microbiologic confirmation of penicillin-susceptible pneumococcal pneumonia in the absence of penicillin allergy . These prescribing patterns may contribute to selection pressure associated with fluoroquinolone-resistant gram-positive and gram-negative bacteria Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality . We assessed this issue in a prospect i ve , multicenter , international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae . The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models . The 14-day mortality was not significantly different for the two groups . However , among critically ill patients , combination antibiotic therapy was associated with lower 14-day mortality ( 23.4 versus 55.3 % , p = 0.0015 ) . This improvement in survival was independent of country of origin , intensive care unit support , class of antibiotics , or in vitro activity of the antibiotics prescribed . Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness The value of blood cultures in community-acquired pneumonia ( CAP ) has been question ed . At issue is the potential for blood cultures to change management . We prospect ively studied the yield and impact of blood cultures in patients admitted with CAP . Two hundred and nine subjects had at least two blood cultures prior to receiving antibiotics . The severity of CAP was grade d using the Pneumonia Severity Index ( PSI ) . Twenty-nine patients ( 13.9 % ) had a pathogen identified by blood culture . The yield of blood cultures increased with PSI grade ( I--5.3 % , II--10.2 % , III--10.3 % , IV--16.1 % , V--26.7 % ) , as did the likelihood of blood cultures changing antibiotic therapy ( I to III--0 % , IV--9.7 % , V--20.0 % ) . One hundred and seventy-nine ( 85.6 % ) patients received a quinolone , limiting the impact of pathogens resistant to beta-lactams . Four of 16 patients ( 25.0 % ) with a culture ( blood or sputum)-guided change in antibiotic therapy died , compared to five of 31 patients ( 16.1 % ) who had an empiric change . Blood cultures are of minimal value in mild to moderate CAP , and should be limited to patients with PSI grade IV or V CAP unless a specific risk factor for pathogens resistant to the empiric therapy is present STUDY OBJECTIVE To assess the value of the initial microbiological studies ( MBS ) , consisting of sputum Gram 's stains , sputum cultures , and blood cultures , in the etiologic diagnosis of community-acquired pneumonia ( CAP ) without comorbidity . DESIGN A prospect i ve study of 74 adult patients hospitalized with nonsevere CAP empirically treated according to the American Thoracic Society guidelines ( ATS-GL ) and evaluated with Gram 's stains and cultures of valid sputum specimens and blood cultures . SETTING University-affiliated community hospital . RESULTS Gram 's stain of a valid sputum specimen failed to identify the etiologic agent in all patients . Sputum cultures identified pathogens in only four patients ( 5 % ) . The results of all blood cultures were negative . All patients responded to the initial empiric antibiotic coverage selected according to the ATS-GL , and the results of the initial MBS had no clinical impact . CONCLUSION The initial MBS , such as sputum Gram 's stains , sputum cultures , and blood cultures , have no value in the management of nonsevere CAP without comorbid factors BACKGROUND It is unclear how often blood culture results influence empiric antibiotic regimens . METHODS To assess the frequency of antibiotic modification and the rates of proper documentation of blood culture results by house staff physicians , we prospect ively evaluated 226 episodes of bacteremia in 199 patients . RESULTS Antibiotics were changed in 49.6 % of episodes of true bacteremias . Physicians were more likely to change therapy if gram-negative rods ( odds ratio [ OR ] , 3.19 ) or Staphylococcus aureus ( OR , 3.12 ) were isolated , if the blood culture was obtained in the first 7 days of hospitalization ( OR , 1.9 ) , or if house staff physicians properly documented the culture results in the medical chart ( OR , 3.8 ) ( all P values , < .05 ) . Documentation of positive blood culture results by house staff physicians was absent in 26 % of patients , and it was observed less often in patients on the surgical service ( OR , 0.35 ; P = .004 ) or if a contaminant was recovered ( OR , 0.24 ; P < .001 ) . Eighty-three percent of " true-positive " blood cultures , as compared with 55 % of " contaminated " blood cultures , were documented with a note in the medical records ( P < .0001 ) . Rates of documentation were higher for gram-negative rods , for patients who were already receiving antibiotic therapy , and for those who had a change of therapy after the culture results became available ( all P values , < .05 ) . A multivariate logistic regression model showed that documentation of the blood culture result ( OR , 1.78 ; P = .006 ) or a positive culture within 7 days of hospitalization ( OR , 1.49 ; P = .01 ) was independently associated with a change in therapy . CONCLUSIONS In a significant proportion of patients with bacteremia , the blood culture result may not be the most important factor that determines antibiotic choice . Bacteremia is not adequately documented by house staff physicians in up to a quarter of patients |
512 | 27,000,311 | Effectiveness of supplements for secondary dysmenorrhoea There was no strong evidence of benefit for melatonin compared to placebo for dysmenorrhoea secondary to endometriosis ( data were unsuitable for analysis ) .
There was no evidence of a difference between the groups but data were too scanty to reach any conclusions about safety .
There is no high quality evidence to support the effectiveness of any dietary supplement for dysmenorrhoea , and evidence of safety is lacking . | BACKGROUND Dysmenorrhoea refers to painful menstrual cramps and is a common gynaecological complaint .
Conventional treatments include non-steroidal anti-inflammatory drugs ( NSAIDs ) and oral contraceptive pills ( OCPs ) , which both reduce myometrial activity ( contractions of the uterus ) .
A suggested alternative approach is dietary supplements .
OBJECTIVES To determine the efficacy and safety of dietary supplements for treating dysmenorrhoea . | Background : Dysmenorrhea is a common gynecologic disorder affecting as many as 60 % of menstruating women . In the United States , work absenteeism due to dysmenorrhea is estimated to be 600 million work hours per year , and the economic consequences are estimated at $ 2 billion per year ; therefore , it is a public problem nowadays . Aim : The purpose of this study was to compare the effects of combination of fennel extract/vitamin E with ibuprofen on the intensity of pain in primary dysmenorrhea among the students of Tabriz city in 2007 - 2009 . Material s and Methods : This study was done by using double-blinded quasi-experimental research method . After taking the required licenses from ethics committee , 68 students from Medical and Tabriz universities , who were living in the dormitory , suffering from primary dysmenorrhea , and were eligible for the study , were r and omly divided into two groups of 34 students each ( the two groups used combination of fennel extract/vitamin E and ibuprofen cross-over form in the 2 months ) . We used Visual Analogue Scale ( VAS ) tool for ranking the intensity of the pain . Data analysis was done by using SPSS Ver . 14 . Results : The mean of peak pain intensity in the first , second , third , sixth , and forty-eighth hours in the group that had used combination of fennel extract/vitamin E was lower than the group that had used ibuprofen , and statistical differences were observed between the two groups in the first and second hours ; combination of fennel extract/vitamin E was more effective than ibuprofen in the first hour ( P < 0.03 ) and second hour ( P < 0.04 ) . Conclusion : Combination of fennel extract/vitamin E is effective on decreasing the intensity of pain of primary dysmenorrhea , and it is advised to those who can not use chemical drugs Background Zingiber officinale R. rhizome ( ginger ) is a popular spice that has traditionally been used to combat the effects of various inflammatory diseases . The aim of this study was to evaluate the effects of ginger on pain relief in primary dysmenorrhea . Method This was a r and omized , controlled trial . The study was based on a sample of one hundred and twenty students with moderate or severe primary dysmenorrhea . The students were all residents of the dormitories of Shahed University . They were r and omly assigned into two equal groups , one for ginger and the other for placebo in two different treatment protocol s with monthly intervals . The ginger and placebo groups in both protocol s received 500 mg capsules of ginger root powder or placebo three times a day . In the first protocol ginger and placebo were given two days before the onset of the menstrual period and continued through the first three days of the menstrual period . In the second protocol ginger and placebo were given only for the first three days of the menstrual period . Severity of pain was determined by a verbal multidimensional scoring system and a visual analogue scale . Results There was no difference in the baseline characteristics of the two groups ( placebo n = 46 , ginger n = 56 ) . The results of this study showed that there were significant differences in the severity of pain between ginger and placebo groups for protocol one ( P = 0.015 ) and protocol two ( P = 0.029 ) . There was also significant difference in duration of pain between the two groups for protocol one ( P = 0.017 ) but not for protocol two ( P = 0.210 ) . Conclusion Treatment of primary dysmenorrhea in students with ginger for 5 days had a statistically significant effect on relieving intensity and duration of pain . Trial registration I RCT OBJECTIVE To evaluate the impact of valerian-a herb with sedative effects and antispasmodic effects on smooth muscles-on the severity of dysmenorrhea . METHODS In a double-blind , r and omized , placebo-controlled trial , 100 students were r and omly assigned to receive valerian ( n=49 ) or placebo ( n=51 ) . Valerian ( dose 255 mg ) was given 3 times daily for 3 days beginning at the onset of menstruation , for 2 consecutive menstrual cycles . At baseline and during the intervention cycles , the pain severity was evaluated with a visual analog scale and the systemic manifestations were assessed using a multidimensional verbal scale . RESULTS The pain severity at baseline did not differ significantly between the groups . After the intervention , the pain severity was significantly reduced in both groups ( P<0.001 ) , but the extent of the reduction was larger in the valerian group , with the difference between the 2 groups being statistically significant ( P<0.05 ) . The total scores of the systemic manifestations associated with dysmenorrhea decreased after the intervention , but there was no significant difference between the groups , with the exception for syncope ( P<0.05 ) . CONCLUSION Valerian seems to be an effective treatment for dysmenorrhea , probably because of its antispasmodic effects Background : Dysmenorrhea has negative effects on women 's life . Due to side-effects of chemical drugs , there is growing trend toward herbal medicine . The aim of this study was to assess the effect of Dill compared to mefenamic acid on primary dysmenorrhea . Material s and Methods : This double-blind , r and omized , clinical trial study was conducted on 75 single female students between 18 and 28 years old educating in Nursing and Midwifery School and Paramedical Faculty of Qom University of Medical Sciences of Iran in 2011 . They were allocated r and omly into one of the three groups : In Dill group , they took 1000 mg of Dill powder q12h for 5 days from 2 days before the beginning of menstruation for two cycles . Other groups received 250 mg mefenamic acid or 500 mg starch capsule as placebo , respectively . Dysmenorrhea severity was determined by a verbal multidimensional scoring system and a visual analog scale ( VAS ) . Students with mild dysmenorrhea were excluded . Data were analyzed by SPSS using the descriptive statistic , paired- sample s t-test , Wilcoxon signed-rank test , Mann-Whitney test , and Kruskal-Wallis test . Results : There were no significant differences between three groups for demographic or descriptive variables . Comprising the VAS showed that the participants of Dill and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after treatment , whereas in the placebo group this was only significant in the 2nd month ( P < 0.05 ) . Conclusion : Dill was as effective as mefenamic acid in reducing the pain severity in primary dysmenorrhea . Further studies regarding side-effects of Dill and its interactivity are recommended OBJECTIVE Wujijing Oral Liquid ( WJJ ) contained principally the flesh essence of the black-boned chicken . As a kind of food and medicine in China , it was used to treat the menstrual disturbance traditionally , but the exact mechanism of the action was not yet clear . The clinical effects of the WJJ on the symptoms of the menstrual disturbance and the reproductive hormones were studied in this paper . MATERIAL S AND METHODS The 53 women with the menstrual disturbance were selected as the study object , and then they were r and omly divided to receive either WJJ 10mL twice daily ( n=28 ) or the placebo ( n=25 ) from the 1st day after menstrual flow for 2 menstrual cycles . On the 1st day after the discontinuation of the medication but before the treatment , the scores for the menstrual pattern and the related symptoms were obtained and the blood sample s were collected to test the reproductive hormones . The serum levels of the follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , prolactin ( PRL ) and estradiol ( E2 ) were examined by enzyme-linked immunosorbent assay ( ELISA ) . The levels of progesterone ( P ) and testosterone ( T ) in serum were measured by the radioimmunoassay . RESULTS The score for the primary and related symptoms of the menstruation was increased significantly among patients treated with the WJJ . The differences on the FSH , PRL , and E2 levels of patients were significant before and after the treatment with WJJ . Comparing the WJJ group and the placebo group , the levels of P and T differed significantly after treatment . The oral liquid of WJJ was found to be safe , as it did not cause any change in the hepatic and renal functional parameters . CONCLUSION The oral liquid of Wujijing could improve the menstrual disturbance and were generally safe and well tolerated . The possible mechanism could be associated with its effects in reinforcing the kidney and regulating the hypothalamus-pituitary-ovary axis ( HPOA ) Our objective was to examine the effect of an Iranian herbal drug in the treatment of primary dysmenorrhea . A r and omized , double-blind , placebo-controlled pilot trial among 180 female students at Isfahan University dormitory aged 18 to 27 who suffered from primary dysmenorrhea was undertaken . The participants were r and omly divided into three groups : herbal drug , mefenamic acid , and placebo . The herbal drug group was given 500 mg of highly purified saffron , celery seed , and anise ( SCA ) extracts three times a day for three days , starting from the onset of bleeding or pain . Participants were followed for two to three cycles from the beginning of menstruation through the three days of bleeding . Main outcome measures were the severity and duration of pain at 2 and 3 months . A visual analogue scale was used to record pain . There were statistically significant reductions in pain scores and pain duration scores in the groups that took SCA ( P < . 001 ) and mefenamic acid ( P < . 01 ) . The decrease in pain score was reflected by a significant reduction in other drug use among the treatment groups compared with the women in the placebo group . The magnitude of the reduction was significantly greater in the SCA group than in the mefenamic acid and placebo groups . Both drugs effectively relieved menstrual pain as compared with the placebo . More clinical trials are needed to establish the efficacy of this herbal drug Objective Preliminary evaluation of efficacy and safety of uzara use in treatment of moderate and severe primary dysmenorrhea in comparison to ibuprofen . Material s and Methods This r and omized , comparative two way cross-over study comprised 60 single female students at Faculty of Medicine , Ain Shams University , Egypt , aged 19–28 years with moderate ( n = 46 ) or severe ( n = 14 ) primary dysmenorrhea . Participants were r and omized to take either uzara ( 80 mg/8 hours for two doses , then 40 mg/8 hours ) then ibuprofen ( 400 mg/6 hours ) in two subsequent cycles or vice versa . The pain intensity , using VAS , was recorded immediately before taking the medication ( 0 hour ) and after 4 , 12 , 24 , 48–60 , 96–120 hours . Main outcome measures included effectiveness of pain relief defined as drop of VAS to 3 or less , patient 's global evaluation of the drug , absence from school , the use of a rescue medication , and , in those who continued the treatment , the pain intensity difference ( PID ) at different points after start of medication and its sum ( SPID ) . Results Uzara was comparably effective to ibuprofen ( 78.3 % vs. 86.7 % of cycles ; respectively ) , with comparable rates of effectiveness on global evaluation ( being around 50 % for either drug ) , and rates of school absences ( 11.7 % vs. 13.3 % ; respectively ) . The need for rescue medication was different ( 18.3 % and 10 % ; respectively ) , albeit with no statistical significance . The means of PID at different time points and SPID were comparable , with significantly lower average mean of VAS scores compared to that felt with no medication ( 1.6 vs. 6.8 , p<0.001 ) . Side effects were less with uzara than ibuprofen ( 0 % vs. 8.3 % , p<0.05 ) . Conclusions Uzara might be as effective as ibuprofen in management of primary dysmenorrhea but with less side effects . These findings need to be confirmed by a properly design ed trial with a larger sample size . Trial Registration Current Controlled Trials IS RCT Background : Primary dysmenorrhea refers to the occurrence of painful menstrual cramps of uterus and is considered as a gynecological complaint . The common treatment for this problem is medical therapy such as mefenamic acid [ non-steroidal anti-inflammatory drugs ( NSAIDs ) ] and oral contraceptive pills , both of which work by reducing myometrial activity . Fennel contains an antispasmodic and anethol agents and may be helpful for management of primary dysmenorrhea . Material and Methods : The aim of this study was to evaluate the effects of oral fennel drop for treating primary dysmenorrhea . Sixty college students suffering from primary dysmenorrhea were r and omly assigned to two groups and followed up for two cycles . Statistical analysis was performed using SPSS version 16 . P < 0.05 was considered to be statistically significant . Parametric and non-parametric tests were adopted . Results : Comparison of pain intensity in the two groups showed that there was no significant difference in pain relief between the two groups . Comparison of bleeding severity in the study group before and after intervention was demonstrated from the first day to the fifth day ( PV on first day , second day , third day , fourth day , and fifth day 0.948 , 0.330 , 0.508 , 0.583 , 0.890 , respectively ) . Conclusion : It seems that fennel can be effective in reducing the severity of dysmenorrhea , but it has an unpleasant taste in view of most of the volunteers Background : Different therapeutic methods have been applied for the treatment of dysmenorrhea and the method with the lesser side effects is preferred . The aim of this study was to compare the effects of herbal products ( fennelin and vitagnus ) and mefenamic acid in the treatment of primary dysmenorrhea . Material s and Methods : This ouble-blind clinical trial was carried out in 105 students with mild and moderate dysmenorrhea . The students were r and omly divided into four groups which received the extracts of fennelin and vitagnus , mefenamic acid , and placebo , respectively . Severity of pain was detected by the Visual Analog Scale ( VAS ) during one cycle before and two cycles after the intervention . Data were analyzed by SPSS version 16 and ( P < 0.05 was considered significant . Results : Demographic characteristics of the students were similar in the four groups . There was no significant difference in the mean of severity of dysmenorrhea during one cycle before the intervention between the four groups , but the difference was significant during two cycles after the intervention . Fennelin had similar effects as vitagnus on dysmenorrhea . Mefenamic acid had less effect than both the drugs ( P < 0.05 ) . Conclusion : Fennelin and vitagnus had higher effect than mefenamic acid . Use of these products is suggested for dysmenorrhea Background : Dysmenorrhea is one of the most common types of cyclic pain that affects 50 % of women and girls in their menstrual ages . Because of the side-effects and contraindications of chemical medicines , using herbs has been investigated in treating dysmenorrhea . Objectives : The aim of this study was to determine the effect of Rosa damascena extract on primary dysmenorrhea among the students of Kowsar dormitory in Tabriz University of Medical Sciences . Material s and Methods : This study was performed in Iran on 92 single 18 - 24 year old students with BMI : 19 - 25 and obtaining pain intensity score of 5 - 8 in Visual Analogue Scale that were r and omly classified and included in two groups of 46 persons . The participants received two capsules of Mefenamic Acid and Rosa damascena with the similar physical properties in two consecutive cycles per 6 hours for 3 days in a cross-over form . The data were collected through the question naire of demographic characteristics and check-list of visual analogue scale . Descriptive statistics and repeated measurement test and independent sample s t test by using SPSS ( 13/win ) were used in order to determine and compare the effects of two drugs on dysmenorrheal pain intensity of the groups . Results : There was a significant difference between the average of pain intensity at different hours of measurement in each group after the end of first cycle and second cycle ( P < 0.001 ) . There was no significant difference between the average of pain intensity in two groups in the first cycle ( P = 0.35 ) and second cycle ( P = 0.22 ) . Conclusions : In this study ¸ Rosa damascena and Mefenamic acid had similar effects on pain intensity of primary dysmenorrhea . With further studies , Rosa damascena which has no chemical side effects¸ can be suggested for treating primary dysmenorrhea OBJECTIVE To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy . DESIGN R and omized comparative trial . SETTING University hospital . PATIENT(S ) Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV ( r-AFS ) . INTERVENTION(S ) Six months of placebo ( n = 110 ) versus GnRH-a ( tryptorelin or leuprorelin , 3.75 mg every 28 days ) ( n = 39 ) or continuous estroprogestin ( ethynilestradiol , 0.03 mg plus gestoden , 0.75 mg ) ( n = 38 ) versus dietary therapy ( vitamins , minerals salts , lactic ferments , fish oil ) ( n = 35 ) . MAIN OUTCOME MEASURE(S ) Painful symptoms ( visual analogue scale score ) and quality -of-life endometriosis-related symptoms ( SF-36 score ) at 12 months ' follow-up . RESULT ( S ) Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups . Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain . Surgery plus placebo showed significative decrease in dyspareunia scores . Postoperative medical and dietary therapy allowed a better quality of life than placebo . CONCLUSION ( S ) Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life STUDY OBJECTIVES To assess the effectiveness of fennel on primary dysmenorrhea symptoms and menorrheal duration . DESIGN Clinical trial study . SETTING Islamic Azad University , Toyserkan . PARTICIPANTS 80 female students were r and omly divided in to two groups of intervention ( n = 40 ) and control ( n = 40 ) . INTERVENTIONS The intervention group was given one soft capsule Fennel ( 30 mg ) every 4 hours , 3 days before menstruation till the 5th day and continued for 3 months . The control group received no medication . MAIN OUTCOME MEASURES The severity of sample s pain was grade d using a visual analogue scale . 5 st and ard question naires include of Visual analog scale pain ( VAS ) , McGill pain question naire , the range of stress about dysmenorrheal ( VASA ) , Perceived stress scale , Well being scale were filled out in intervals of before , during and after fennel capsule uptake . Data were analyzed by SPSS 17 software . P < .05 was considered to be statistically significant . RESULTS The mean of nausea intensity and weakness decreased to 1.93 , and 2.88 after 3 months , whereas they were 2.37 , 6.65 in control group which indicated a significant difference . Reduce the duration of menstrual period , a significant difference was found after two and three months of use . Concern in terms of quality and feelings of well-being after 1 and 3 months , was observed significant difference compared with before using . CONCLUSION Considering the safety of herbal medicines , this drug can use to relieve dysmenorrheal signs and menstrual duration Background : Dysmenorrhea is one of the most common medical problems in gynecology causing several problems in the personal and social life of women . This study was conducted to compare the effect of thymus vulgaris and ibuprofen on the treatment of primary dysmenorrhea Methods : This clinical study was conducted on 84 students of Babol University of Medical Sciences with primary dysmenorrhea . The students were r and omly assigned to three groups receiving thymus vulgaris , ibuprofen and placebo . In all three groups , with the beginning of pain , 200 mg capsules and 25 drops of essential oil were given every 6 hours for two consecutive cycles . Pain intensity used the visual scale before and one hour after each dose for 48 hour after starting medication . The data were collected and analyzed . This study was registered in the Iranian Registry of Clinical Trial ( www.i rct .ir ) with registration number ID : I RCT 201101245683N1 Results : The mean age of participants was 20.5±1.8 years . Both thymus vulgaris and ibuprofen were effective to reduce the pain severity of dysmenorrhea . Before treatment , the mean pain intensity in thymus vulgaris , ibuprofen and placebo groups were 6.57±2.02 , 5.30±2.23 and 6.18±1.78 , respectively and after treatment decreased to 1.21±1.06 , 1.48±1.62 and 3.54±2.26 , respectively . Reduction of pain severity was not statistically significant between the two medications , however it was significant for each drug compared with placebo ( p<0.001 ) . Conclusion : The results suggest that thymus vulgaris as well as ibuprofen can be effective in reducing the severity of pain and spasm in primary dysmenorrhea Background Primary dysmenorrhea is a prevalent disorder and its unfavorable effects deteriorates the quality of life in many people across the world . Based on some evidence on the characteristics of fenugreek as a medical plant with anti-inflammato-ry and analgesic properties , this double-blind , r and omized , placebo controlled trial was conducted . The main purpose of the study was to evaluate the effects of fenugreek seeds on the severity of primary dysmenorrhea among students . Methods Unmarried Students were r and omly assigned to two groups who received fenugreek ( n = 51 ) or placebo ( n = 50 ) . For the first 3 days of menstruation , 2–3 capsules containing fenugreek seed powder ( 900 mg ) were given to the subjects three times daily for two consecutive menstrual cycles . Pain severity was evaluated using a visual analog scale and systemic symptoms were assessed using a multidimensional verbal scale . Results Pain severity at baseline did not differ significantly between the two groups . Pain severity was significantly reduced in both groups after the intervention ; however , the fenugreek group experienced significantly larger pain reduction ( p < 0.001 ) . With respect to the duration of pain , there was no meaningful difference between the two cycles in the placebo group ( p = 0.07 ) but in the fenugreek group , the duration of pain decreased between the two cycles ( p < 0.001 ) . Systemic symptoms of dysmenorrhea ( fatigue , headache , nausea , vomiting , lack of energy , syncope ) decreased in the fenugreek seed group ( p < 0.05 ) . No side effects were reported in the fenugreek group . Conclusion These data suggest that prescription of fenugreek seed powder during menstruation can reduce the severity of dysmenorrhea A study in Kerman , Islamic Republic of Iran in 2002 compared the effectiveness of fennel and mefenamic acid on pain relief in primary dysmenorrhoea . Two groups of high-school girls ( mean age 13 years ) suffering dysmenorrhoea were r and omized to receive fennel extract ( n = 55 ) or mefenamic acid ( n = 55 ) for 2 months . In the fennel group , 80 % of girls and in the mefenamic acid group , 73 % of girls showed complete pain relief or pain decrease , while 80 % in the fennel group and 62 % in the mefenamic acid group no longer needed to rest . There was no significant difference between the 2 groups in the level of pain relief OBJECTIVES To compare the effects of ginger , mefenamic acid , and ibuprofen on pain in women with primary dysmenorrhea . METHODS This was a double-blind comparative clinical trial conducted from September 2006 to February 2007 . Participants were 150 students ( 18 years old and over ) with primary dysmenorrhea from the dormitories of two medical universities who were alternately divided into three equal groups . Students in the ginger group took 250 mg capsules of ginger rhizome powder four times a day for three days from the start of their menstrual period . Members of the other groups received 250 mg mefenamic acid or 400 mg ibuprofen capsules , respectively , on the same protocol . A verbal multidimensional scoring system was used for assessing the severity of primary dysmenorrhea . Severity of disease , pain relief , and satisfaction with the treatment were compared between the groups after one menstruation . RESULTS There were not significant differences between groups in baseline characteristics , p > 0.05 . At the end of treatment , severity of dysmenorrhea decreased in all groups and no differences were found between the groups in severity of dysmenorrhea , pain relief , or satisfaction with the treatment , p > 0.05 . No severe side effects occurred . CONCLUSION Ginger was as effective as mefenamic acid and ibuprofen in relieving pain in women with primary dysmenorrhea . Further studies regarding the effects of ginger on other symptoms associated with dysmenorrhea and efficacy and safety of various doses and treatment duration s of ginger are warranted Abstract Background : The aim of this study was to investigate and evaluate the efficacy of Rheum emodi in the management of primary dysmenorrhoea . Methods : A r and omized , single-blind , st and ard controlled trial compared efficacy of R. emodi against mefenamic acid on diagnosed subjects of primary dysmenorrhoea for three consecutive cycles . Experimental group ( n=30 ) received capsules of R. emodi powder two times a day , two days before the expected date of menstruation , and continued first three days of menstruation , while control group ( n=15 ) participants received mefenamic acid capsules three times a day on the same protocol . The primary outcome measures were reduced in severity and duration of pain , assessed by visual analogue scale ( VAS ) and verbal multidimensional scoring system ( VMSS ) , and secondary outcome measures were overall improvement of dysmenorrhoea and improved in quality of life ( QOL ) . Statistical analysis was done by repeated measures analysis of variance and Chi-square/Fisher Exact test . Results : The menstrual pain was significantly decreased in both groups after three-cycle intervention . Significant changes were observed in VAS ( p<0.001 ) and VMSS ( p<0.001 ) in the experimental group . There is a significant ( p<0.001 ) reduction in duration of pain in both the groups . Associated symptoms and QOL were markedly improved after treatment ( p<0.001 ) . Conclusions : It has been clear from the above result that R. emodi is an effective herb in alleviating symptoms of primary dysmenorrhoea . It can serve as an alternative treatment without any apparent side effects . These results deserve further investigations OBJECTIVE To evaluate the effect of vitamin E on the reduction of pelvic pain in women with primary dysmenorrhea and to compare its effect with placebo . STUDY DESIGN A double-blind r and omized clinical trial was performed on 120 women suffering from primary dysmenorrhea . They were r and omly assigned into 2 groups , and 94 women finished the study . In the study group ( n = 42 ) 400 IU/day of vitamin E was prescribed starting 2 days before the beginning of menstruation and continuing for a total of 5 days , for 2 consecutive cycles . In the control group ( n = 52 ) a placebo was prescribed . Pain severity was evaluated using the Visual Analogue Scale for 1 month before the study and during the 2 months of study . RESULTS Pain severity during the first month of the study was 5.41 + /- 2.4 in the study group and 5.76 + /- 2.08 in the control group and 4.73 + /- 1.89 and 5.35 + /- 2.05 in the study and control groups , respectively , during the second month of the study . Pain severity during the first and second months of treatment with vitamin E and placebo was lower than the pain severity before treatment . The mean reduction of pain in the study group ( -2.7 + /- 2.1 ) was greater than that in the control group ( -1.8 + /- 2.4 ) during the second month of the study . CONCLUSION Both vitamin E and placebo may reduce the pelvic pain of dysmenorrhea , but vitamin E seems to cause a more significant reduction in pain . With regard to its safety , the study indicates it can be a simple and safe option for the treatment of dysmenorrhea Primary dysmenorrhea is a common gynaecological symptom complex characterized by a painful syndrome occurring predominantly on the first and the second day of the cycle and associated with concomitant autonomic phenomena . In a r and omized double-blind study , the therapeutic effect of magnesium has been investigated in 32 women ( 16 to 42 years old ) who have been treated in the gynaecological outpatient-department at our clinic because of primary dysmenorrhea . The dosage of Magnesiocard comprised 3 X 5 mmol granulate orally on the day preceding menstruation and on the first and the second day of the cycle . At the end of the study , which covered six cycles , we were able to analyze the results in 21 patients , 11 having been treated with magnesium and 10 with placebo . While in the magnesium group only a slight effect was noted on the first day of the cycle under therapy when compared to both the placebo group and the dysmenorrhea disturbances persisting before therapy was started , magnesium had a therapeutic effect on both back pain and lower abdominal pain on the second and the third day of the cycle . Parallel to this therapeutic influence on the symptomatology of dysmenorrhea , a marked reduction in absences from work due to the dysmenorrhea was also noted . The possibilities of magnesium therapy in dysmenorrhea should be investigated further in multicentre studies Primary dysmenorrhea is common among young women and results in their incapacitation ; it can be accompanied by various symptoms that can disrupt their lives . The aim of this r and omized trial was to compare the effect of ginger , zinc sulfate , and placebo on the severity of primary dysmenorrhea in young women . One hundred and fifty high school students were recruited . The participants were divided into three groups . The first group received ginger capsules , the second group received zinc sulfate capsules , and the third group received placebo capsules . All participants took the medications for four days , from the day before the commencement of menstruation to the third day of their menstrual bleeding . The severity of dysmenorrhea was assessed every 24 hours by the pain visual analog scale . The severity of pain was significantly different between , before , and after the intervention in both the ginger and the zinc sulfate groups ( p < .001 ) . Compared with the placebo receiving group , participants receiving ginger and zinc sulfate reported more alleviation of pain during the intervention ( p < .05 ) . Ginger and zinc sulfate had similar positive effects on the improvement of primary dysmenorrheal pain in young women With approximately 25 % of dysmenorrheic patients reporting no improvement with nonsteroidal anti-inflammatory drugs , a study was devised to evaluate the effectiveness of a laparoscopic technique for the interruption of the uterosacral nerves . In a double-blind study of 21 patients with primary dysmenorrhea , 81 % ( 9 of 11 ) reported significant relief from menstrual pain after the surgery . Performed as an outpatient procedure , laparoscopic uterine nerve ablation may alleviate dysmenorrheic complaints when other modalities have failed . Half the treated women reported continued relief of menstrual pain at 12 months . These results suggest that uterosacral nerve interruption may prove an effective alternative treatment for this menstrual disorder Objective To determine whether vitamin E is effective in the treatment of primary dysmenorrhoea OBJECTIVES The hypothesis tested was that menstrual discomfort , e.g. dysmenorrhoea , known to be prostagl and in-mediated , can be influenced by the dietary ratio of n-3 and n-6 polyunsaturated fatty acids . The prostagl and ins derived from marine n-3 fatty acids are normally less aggressive and therefore expected to be associated with milder symptoms . DESIGN The question was surveyed in an epidemiological study based upon self-administered question naires concerning menstrual history , present symptoms , general health , socioeconomic factors , and general dietary habits . Two ( prospect i ve ) 4-day dietary records were used to estimate average daily nutrient intake . SUBJECTS The subjects were recruited by advertising ( about 220 volunteered ) ; 181 healthy Danish women were selected , aged 20 - 45 years ; they were not pregnant and did not use oral contraceptives . RESULTS No correlations were found between socioeconomic or anthropometric data and menstrual problems . On the contrary certain dietary habits , e.g. low intake of animal and fish products , and intakes of specific nutrients , were correlated with menstrual pain . The average dietary n-3/n-6 ratio of women with menstrual pain was 0.24 . It was significantly higher among those with low intake of B12 coincident with low intake of n-3 ( 0.42 , P < 0.001 ) ( chi-square ) , with low n-3 intake coincident with low n-3/n-6 ratio ( 0.42 , P < 0.005 ) , and finally with low intake of B12 coincident with low n-3/n-6 ratio ( 0.47 , P < 0.001 ) . CONCLUSION The results were highly significant and mutually consistent and supported the hypothesis that a higher intake of marine n-3 fatty acids correlates with milder menstrual symptoms OBJECTIVE To assess the effectiveness of ginger in providing relief to patients of primary dysmenorrhoea . METHODS The clinical trial was conducted at Toyserkan Azad University in western Iran from July 10 to September 5 , 2010 . It comprised of 70 female students of the university with primary dysmenorrhoea . The subjects were r and omly divided in to two equal groups and were given either placebo or ginger in capsule form for 3 days in first menstruation cycles . They grade d the severity of their pain using a visual analogue scale . A 5-point Likert scale was used to assess response to treatment . Wilcoxor 's rank-sum test was used to compare the severity of pain in the two groups . RESULTS Compared with the baseline , the decrease in the visual analogue scores of post-therapy pain in the ginger group was significantly greater than that for placebo group . In the ginger group , 29 ( 82.85 % ) subjects reported an improvement in nausea symptoms , compared with 16 ( 47.05 % ) in the placebo group . CONCLUSION Ginger is effective in minimising the pain severity in primary dysmenorrhoea Primary dysmenorrhea occurs in as many as 50 % of female adolescents and is associated with significant decreases in academic performance , sports participation , and socialization with peers . Complementary and alternative medicine treatment options are of interest to patients and health care providers . The use of rose tea to alleviate menstrual pain has long been a part of folk knowledge around the world but has not been studied scientifically . To determine the effectiveness of drinking rose tea as an intervention for reducing pain and psychophysiologic distress in adolescents with primary dysmenorrhea , 130 female adolescents were r and omly assigned to an experimental ( n = 70 ) and a control ( n = 60 ) group . Preintervention and postintervention data at 1 month , 3 months , and 6 months were gathered on the biopsychosocial outcomes of dysmenorrhea . The results showed that compared with the control group , the experimental group perceived less menstrual pain , distress , and anxiety and showed greater psychophysiologic well-being through time , at 1 , 3 , and 6 months after the interventions . Findings suggest that drinking rose tea is a safe , readily available , and simple treatment for dysmenorrhea , which female adolescents may take to suit their individual needs OBJECTIVE To examine whether dietary supplementation with omega-3 fatty acids relieved symptoms of primary dysmenorrhea . METHODS Women aged 18 - 22 years with primary dysmenorrhea were enrolled in a double-blind crossover study . Women assigned to group 1 ( n=47 ) received 1 omega-3 capsule daily for 3 months , followed by placebo for 3 months . Women in group 2 ( n=48 ) received placebo for 3 months , followed by omega-3 for 3 months . A washout period was performed in both groups . Participants used 400 mg of ibuprofen as a rescue dose if severe menstrual pains were experienced . RESULTS A marked reduction in pain intensity was observed after 3 months of treatment with omega-3 fatty acids ( P<0.05 ) . Women who received omega-3 fatty acids required fewer rescue doses than women who received placebo ( P<0.05 ) . The mean numbers of ibuprofen tablets used after 3 months with omega-3 fatty acids were 4.3±2.1 ( group 1 ) and 3.2±2.5 ( group 2 ) ; the mean numbers of tablets used after 3 months of placebo were 5.3±2.2 ( group 1 ) and 6.0±2.6 ( group 2 ) ( P=0.001 for both ) . CONCLUSION Supplementation with omega-3 fatty acids reduced the symptom intensity of primary dysmenorrhea . Supplementation efficacy was sufficient to decrease the ibuprofen rescue dose The purpose of the present research work was to carry out clinical study on primary dysmenorrhea to comparatively examine the coded herbal drug formulation “ Dysmo-off ” with authentic allopathic medicine “ Diclofenac sodium ” ( NSAIDs ) . A r and om controlled clinical trial was conducted to compare the efficacy and safety of coded herbal medicinal treatments Dysmo-off with Diclofenac sodium/Phenylacetic acid . These evaluations were based on verbal rating scale so as to ascertain the rate of analgesic effects on dysmenorrhoeic pain . The patients were r and omly allocated with the ratio of 1:2 for controlled treatment with nonsteroidal anti-inflammatory drugs ( NSAIDs ) ( n = 40 ) received Diclofenac sodium tablets twice daily for 4 days ( 50 mg one day prior to and three days after the menstruation ) , and test treatment with Dysmo-off ( n = 80 ) received powdered Dysmo-off twice daily for four days ( 5 g one day prior to and three days after the menstruation ) . Treatment lasted for 4 consecutive menstrual cycles . Hemoglobin , ESR and ultrasound were measured at baseline during study . All subjects were clinical ly studied and completed the assigned therapy during the period May 2001 to June 2004 Objective To study the effect of vitamin E in the treatment of primary dysmenorrhoea OBJECTIVE This clinical study was conducted to investigate the efficacy and safety of an oriental herbal medicine native to Korea , Chiljehyangbuhwan , in treating primary dysmenorrhea . DESIGN AND SETTING A total of 100 primary dysmenorrhea patients who visited Kyung Hee University Korean Oriental Medicine Hospital between July 19 2004 and August 27 2004 were recruited . Secondary or drug-related dysmenorrhea was screened out through interviews and examination . The patients were grouped by fixed blocked r and omization and administered either Chiljehyangbuhwan or placebo for one menstrual period in a double blind model . Visual Analogue Scale ( VAS ) , Verbal Rating Scale ( VRS ) , and Multidimensional Verbal Rating Scale ( MVRS ) were used to evaluate dysmenorrhea severity . A total of 71 patients who passed the screening test and remained to the last were divided into either placebo or Chiljehyangbuhwan group , and each were further split into smaller subsets ( indication , non-indication , and unspecified group ) according to Korean Oriental medical diagnosis . RESULTS In the non-indication group , the placebo and Chiljehyangbuhwan group did not show significant difference in VAS , VRS , and MVRS scores before medication ( 1st VAS , 1st VRS , 1st MVRS ) , after medication ( 2nd VAS , 2nd VRS , 2nd MVRS ) , and in changes in scores before and after ( DeltaVAS , DeltaVRS , DeltaMVRS ) . In the indication group , the placebo and Chiljehyangbuhwan group showed significant difference in change in VAS and MVRS scores ( DeltaVAS and DeltaMVRS ) . No evidence of toxicity could be found , and no serious adverse reactions to Chiljehyangbuhwan were reported . CONCLUSION The results suggest that Chiljehyangbuhwan is effective and safe in treating primary dysmenorrhea when prescribed appropriately under Korean Oriental medical diagnosis OBJECTIVE This exploratory study was design ed to determine whether dietary calcium and manganese affect menstrual symptoms in healthy women . STUDY DESIGN Ten women with normal menstrual cycles completed the Menstrual Distress Question naire each cycle during a 169-day , live-in metabolic study of calcium and manganese nutrition . Women were assigned in a double-blind , Latin-square manner to each of four 39-day dietary periods : 587 or 1336 mg calcium per day with 1.0 or 5.6 mg manganese per day . Responses were analyzed by repeated- measures analysis of variance . RESULTS Increasing calcium intake reduced mood , concentration , and behavior symptoms generally ( p < or = 0.05 ) , reduced pain during the menstrual phase of the cycle ( p = 0.034 ) , and reduced water retention during the premenstrual phase ( p = 0.041 ) . In spite of increasing calcium intake , lower dietary manganese increased mood and pain symptoms during the premenstrual phase ( p < or = 0.05 ) . CONCLUSION Dietary calcium and manganese may have a functional role in the manifestation of symptomatology typically associated with menstrual distress PRIMARY OBJECTIVE To evaluate the effectiveness of Neptune Krill Oil ( NKO ) for the management of premenstrual syndrome and dysmenorrhea . SECONDARY OBJECTIVE To compare the effectiveness of NKO for the management of premenstrual syndrome and dysmenorrhea with that of omega-3 fish oil . METHODS / DESIGN Double-blind , r and omized clinical trial . SETTING Outpatient clinic . PARTICIPANTS Seventy patients of reproductive age diagnosed with premenstrual syndrome according to the Diagnostic and Statistical Manual of Mental Disorders , Third Edition , Revised ( DSM-III-R ) . INTERVENTIONS Treatment period of three months with either NKO or omega-3 fish oil . OUTCOME MEASURES Self- Assessment Question naire based on the American College of Obstetricians and Gynecologists ( ACOG ) diagnostic criteria for premenstrual syndrome and dysmenorrhea and number of analgesics used for dysmenorrhea . RESULTS In 70 patients with complete data , a statistically significant improvement was demonstrated among baseline , interim , and final evaluations in the self assessment question naire ( P < 0.001 ) within the NKO group as well as between-group comparison to fish oil , after three cycles or 45 and 90 days of treatment . Data analysis showed a significant reduction of the number of analgesics used for dysmenorrhea within the NKO group ( comparing baseline vs. 45- vs. 90-day visit ) . The between-groups analysis illustrated that women taking NKO consumed significantly fewer analgesics during the 10-day treatment period than women receiving omega-3 fish oil ( P < 0.03 ) . CONCLUSION Neptune Krill Oil can significantly reduce dysmenorrhea and the emotional symptoms of premenstrual syndrome and is shown to be significantly more effective for the complete management of premenstrual symptoms compared to omega-3 fish oil Objective : Primary dysmenorrhea is defined as painful cramps during menstruation with no pelvic pathology . Due to the adverse effects of Non-Steroidal Anti-Inflammatory Drugs ( NSAIDs ) are considered as the most common pharmacological treatment for this disorder . The present study was conducted to assess the impact of Shirazi Thymus Vulgaris compared to that of Ibuprofen on primary dysmenorrhea . Material s and Methods : A r and omized , single-blind clinical trial was conducted amongst 120 female students ofIlam University of Medical Sciences , aged 18 - 25 years who suffered from primary dysmenorrhea . The participants were r and omly divided into two groups ; one received the herbal and the other classical treatments . The herbal group received 5 ml of the Shirazi Thymus Vulgaris medication that commercially called BronchoT.D , orally four times a day . The classic group received Ibuprofen orally three times a day . A visual analogue scale ( VAS ) was used to record pain severity . Results : Pain severity was reduced in both herbal and classic groups with no significant differences . Pain duration at the first and second month of treatment was also similar between two groups . Conclusions : Shirazi Thymus Vulgaris decreased dysmenorrhea symptoms , which might be attributed to its antispasmodic effects . The herbal Shirazi Thymus Vulgaris can be recommended as an effective medication fortreatment of the primary dysmenorrhea disorder Aims : The purpose of this study is the comparison of the effect of vitamin B1 and fish oil with together on severity and duration of dysmenorrhea , and if it is effective , we can administrate both of them with less complication to compare with other chemical drugs which has many disadvantages . Study Design : High school of Urmia city , between March 2008 and June 2008 . Methodology : This study has a double-blind clinical trial design .240 high school female students with dysmenorrhea by a r and omized Method were followed up in a double-blind , r and omized , placebo-controlled study by dividing into four groups with 60 members . The daily supplement was vit B1 ( 100 mg/day and fish oil pearl 500 mg/day ) , taken as a single dose starting at the beginning of the menstrual cycle and continued for 2 consecutive months . Results : Intensity of pain in three experimental groups ( Vit B1 , fish oil and both of them ) had significant difference comparing placebo group and intensity of pain had reduced . ( p<0.001 ) , ( p=0.018 ) , ( p<0.001 ) VS in placebo group ( p=0.79 ) . Duration of pain had significantly reduced in all three experimental groups compared with placebo group . ( p=0.004 ) , ( p=0.008 ) , ( p<0.001 ) VS in placebo group ( p=0.32 ) . In all of drugs , results ( mean ) was better at the end of the second month than the first month . Conclusion : Fish oil and vit B1 effects on treatment of primary dysmenorrhea were similar , but vit B1 has less complications and it was more acceptable . We mixed them and compared its results with vit B1 , fish oil and placebo separately . Pain duration is the least in Vitamin B1 tablets compare with the others , but its duration was minimum in complex of Vitamin B1 tablets and fish oil capsules . Due to good effects of vitamin B1 and fish oil on symptoms of dysmenorrhea , using of them is suggested OBJECTIVE To assess the efficacy of two different doses of a Psidii guajavae folium extract in the management of primary dysmenorrhea . METHODOLOGY A double-blinded r and omized clinical trial was conducted in 197 women with primary dysmenorrhea . Four intervention groups were defined : two extract doses ( 3 and 6 mg/day ) ; ibuprofen ( 1200 mg/day ) ; placebo ( 3mg/day ) . Participants were followed-up individually for 4 months . The main outcome variable was abdominal pain intensity measured according to a visual analogue scale ( VAS ) . RESULTS The average age of participants was 19 years ; menarche occurred around age 12 years . Participants had menstrual cycles of 28 or 29 days , with menstruation lasting 5 days and mean of pain intensity of 8.2 on the VAS . During each successive treatment cycle , participants experienced a lower pain intensity score . Multiple regression analysis , after adjusting each cycle for baseline pain , treatment compliance and other variables , showed that the group receiving 6 mg/day extract had significantly reduced pain intensity ( p<0.001 ) . This effect was maintained in cycles 2 and 3 , although the reduction in the mean of pain intensity was lower . The group receiving the 3mg/day extract did not show a consistent effect throughout the three cycles . CONCLUSION At a dose of 6 mg/day , the st and ardized phyto-drug ( Psidii guajavae folium extract ) reduced menstrual pain significantly compared with conventional treatment and placebo 50 patients suffering from primary dysmenorrhoea were treated with Magnesium ( Mg 5-longoral , Artesan GmbH ) in a double-blind study . After a six-month period 21 out of 25 women showed a decline of symptoms , only 4 ones reported no therapeutical effect . For monitoring treatment results prostagl and in F2 alpha ( PGF2 alpha ) was measured every second month . On Mg-therapy conditions we achieved a reduction of PGF2 alpha in menstrual blood to 45 % of value before treatment started . As against that 90 % of basic concentration were estimated from women who received a placebo . Probably , the specific therapeutical effect of Mg based on inhibition of bio synthesis of PGF2 alpha but also on its direct muscle relaxant and vasodilatory effect . Beside the PG- synthesis and ovulation inhibitors the use of Magnesium is a potential , natural opportunity to treat primary dysmenorrhoea , which is widely free of side effects Background Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological complaint . Common treatment for dysmenorrhoea is medical therapy such as nonsteroidal anti-inflammatories ( NSAIDs ) or oral contraceptive pills ( OCPs ) which both work by reducing myometrial activity ( contractions of the uterus ) . The efficacy of conventional treatments such as nonsteroidals is considerable , however the failure rate is still often 20 - 25 % . Many consumers are now seeking alternatives to conventional medicine and research into the menstrual cycle suggests that nutritional intake and metabolism may play an important role in the cause and treatment of menstrual disorders . Herbal and dietary therapies number among the more popular complementary medicines yet there is a lack of taxonomy to assist in classifying them . In the US , herbs and other phytomedicinal products ( medicine from plants ) have been legally classified as dietary supplements since 1994 . Included in this category are vitamins , minerals , herbs or other botanicals , amino acids and other dietary substances . For the purpose of this review we use the wider term herbal and dietary therapies to include the assorted herbal or dietary treatments that are classified in the US as supplements and also the phytomedicines that may be classified as drugs in the European Union . Objectives To determine the efficacy and safety of herbal and dietary therapies for the treatment of primary and secondary dysmenorrhoea when compared to each other , placebo , no treatment or other conventional treatments ( e.g. NSAIDS ) . Search methods Electronic search es of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials , CCTR , MEDLINE , EMBASE , CINAHL , Bio extracts , and PsycLIT were performed to identify relevant r and omised controlled trials ( RCTs ) . The Cochrane Complementary Medicine Field 's Register of controlled trials ( CISCOM ) was also search ed . Attempts were also made to identify trials from the National Research Register , the Clinical Trial Register and the citation lists of review articles and included trials . In most cases , the first or corresponding author of each included trial was contacted for additional information . Selection criteria The inclusion criteria were RCTs of herbal or dietary therapies as treatment for primary or secondary dysmenorrhoea vs each other , placebo , no treatment or conventional treatment . Interventions could include , but were not limited to , the following ; vitamins , essential minerals , proteins , herbs , and fatty acids . Exclusion criteria were : mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD . Data collection and analysis Seven trials were included in the review . Quality assessment and data extraction were performed independently by two review ers . The main outcomes were pain intensity or pain relief and the number of adverse effects . Data on absence from work and the use of additional medication was also collected if available . Data was combined for meta- analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data . A fixed effects statistical model was used . If data suitable for meta- analysis could not be extracted , any available data from the trial was extracted and presented as descriptive data . Main results MAGNESIUM : Three small trials were included that compared magnesium and placebo . Overall magnesium was more effective than placebo for pain relief and the need for additional medication was less . There was no significant difference in the number of adverse effects experienced . VITAMIN B6 : One small trial of vitamin B6 showed it was more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6 . MAGNESIUM AND VITAMIN B6 : Magnesium was shown to be no different in pain outcomes from both vitamin B6 and a combination of vitamin B6 and magnesium by one small trial . The same trial also showed that a combination of magnesium and vitamin B6 was no different from placebo in reducing pain . VITAMIN B1 : One large trial showed vitamin B1 to be more effective than placebo in reducing pain . VITAMIN E : One small trial comparing a combination of vitamin E ( taken daily ) and ibuprofen ( taken during menses ) versus ibuprofen ( taken during menses ) alone showed no difference in pain relief between the two treatments . OMEGA-3 FATTY ACIDS : One small trial showed fish oil ( omega-3 fatty acids ) to be more effective than placebo for pain relief . JAPANESE HERBAL COMBINATION : One small trial showed the herbal combination to be more effective for pain relief than placebo , and less additional pain medication was taken by the treatment group . Authors ' conclusions Vitamin B1 is shown to be an effective treatment for dysmenorrhoea taken at 100 mg daily , although this conclusion is tempered slightly by its basis on only one large RCT . Results suggest that magnesium is a promising treatment for dysmenorrhoea . It is unclear what dose or regime of treatment should be used for magnesium therapy , due to variations in the included trials , therefore no strong recommendation can be made until further evaluation is carried out . Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies considered in this review for the treatment of primary or secondary dysmenorrhoea To examine whether dietary supplementation with omega-3 fatty acids from Clupeonella grimmi can relieve symptoms of dysmenorrhoea , we carried out a cross-over clinical trial on 36 girls aged 18 - 22 years . They were r and omly allocated into 2 groups of 18 . Group A received 15 mL fish oil daily ( 550 mg eicosapentaenoic acid ; 205 mg decosahexaenoic acid ) while Group B received placebo . After 3 months , the treatment regimens were swapped . The treatment groups reported a significant difference after 3 months of supplementation with fish oil ( visual analogue scale score 20.9 compared with 61.8 for the placebo ( P= 0.001 ) . There was also a marked reduction in low back pain and abdominal pain ( P < 0.05 ) , and participants needed significantly fewer rescue doses of ibuprofen while using fish oil OBJECTIVES The purpose of the study was to examine whether dietary supplementation with omega-3 fatty acids can relieve symptoms of dysmenorrhea in adolescents . STUDY DESIGN Forty-two adolescents with dysmenorrhea were r and omly allocated to two groups . In the first group 21 girls received fish oil ( 1080 mg icosapentaenoic acid , 720 mg docosahexaenoic acid , and 1.5 mg vitamin E ) daily for 2 months followed by a placebo for an additional 2 months . In the second group 21 girls received placebo for the first 2 months , followed by fish oil for 2 more months . The Cox Menstrual Symptom Scale was used to assess response to treatment . RESULTS There were no significant differences in the Cox Menstrual Symptom Scale between the two groups at baseline after 2 months of placebo administration . After 2 months of treatment with fish oil there was a marked reduction in the Cox Menstrual Symptom Scale from a baseline mean value of 69.9 to 44.0 ( p < 0.0004 ) . CONCLUSIONS This study suggests that dietary supplementation with omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents We evaluated the analgesic effect of Toki-shakuyaku-san ( TSS ) in women who had a combination of " deficiency , " of " Yin , " " cold , " and " stagnated blood " syndromes , and were suffering from dysmenorrhea . A diagnostic scoring system was used for determination of these conditions . We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique , and we followed them for 2 additional cycles . A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo . Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity . To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms , we performed a r and omized , placebo-controlled trial of antioxidant vitamins ( vitamins E and C ) in women with pelvic pain and endometriosis . Fifty-nine women , ages 19 to 41 years , with pelvic pain and history of endometriosis or infertility were recruited for this study . Patients were r and omly assigned to 2 groups : vitamin E ( 1200 IU ) and vitamin C ( 1000 mg ) combination or placebo daily for 8 weeks before surgery . Pain scales were administered at baseline and biweekly . Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy . Our results indicated that after treatment with antioxidants , chronic pain ( " everyday pain " ) improved in 43 % of patients in the antioxidant treatment group ( P = 0.0055 ) compared with the placebo group . In the same group , dysmenorrhea ( " pain associated with menstruation " ) and dyspareunia ( " pain with sex " ) decreased in 37 % and 24 % patients , respectively . In the placebo group , dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia . There was a significant decrease in peritoneal fluid inflammatory markers , regulated upon activation , normal T-cell expressed and secreted ( P ≤ 0.002 ) , interleukin-6 ( P ≤ 0.056 ) , and monocyte chemotactic protein-1 ( P ≤ 0.016 ) after antioxidant therapy compared with patients not taking antioxidants . The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid & NA ; Melatonin reduced pain scores and analgesic use , and improved sleep quality in endometriosis‐associated chronic pelvic pain . Melatonin modulates the secretion of brain‐derived neurotrophic factor independently of its analgesic effect in endometriosis . & NA ; Endometriosis‐associated chronic pelvic pain ( EACPP ) presents with an intense inflammatory reaction . Melatonin has emerged as an important analgesic , antioxidant , and antiinflammatory agent . This trial investigates the effects of melatonin compared with a placebo on EACPP , brain‐derived neurotrophic factor ( BDNF ) level , and sleep quality . Forty females , aged 18 to 45 years , were r and omized into the placebo ( n = 20 ) or melatonin ( 10 mg ) ( n = 20 ) treatment groups for a period of 8 weeks . There was a significant interaction ( time vs group ) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain , dysmenorrhea , dysuria , and dyschezia ( analysis of variance , P < 0.01 for all analyses ) . Post hoc analysis showed that compared with placebo , the treatment reduced daily pain scores by 39.80 % ( 95 % confidence interval [ CI ] 12.88–43.01 % ) and dysmenorrhea by 38.01 % ( 95 % CI 15.96–49.15 % ) . Melatonin improved sleep quality , reduced the risk of using an analgesic by 80 % , and reduced BNDF levels independently of its effect on pain . This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin ’s ability to improve sleep quality . Additionally , the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms |
513 | 30,703,096 | There are significant differences in program impact by gender , with numeracy and literacy differentially positively affected for girls , and by age , with treatment effects larger for the primary school aged sub sample .
There are also significant treatment interactions for those living in households with more treatment-eligible children .
There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility .
Mass deworming of preschool aged children in high prevalence communities in Ug and a result ed in no statistically significant gains in numeracy or literacy 7 - 12 years after program completion .
Point estimates were positive but imprecise ; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects .
However , there is suggestive evidence that deworming was relatively more beneficial for girls , primary school aged children , and children living in households with other treated children . | BACKGROUND Up to 1.45 billion people currently suffer from soil transmitted helminth infection , with the largest burden occurring in Africa and Asia .
Safe and cost effective deworming treatment exists , but there is a debate about mass distribution of this treatment in high prevalence setting s. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high ( > 20 % ) prevalence setting s , and several long run follow up studies of an influential trial have suggested large benefits that persist over time , recent systematic review s have called this recommendation into question . | Abstract Soil-transmitted helminths ( STHs ) infect over one billion people worldwide . There is concern that chronic infection with STHs among school-aged children may detrimentally affect their development , including their health , cognition , and education . However , two recent Cochrane review s examining the impact of deworming drugs for STH on nutrition , hemoglobin , and school performance found that r and omized controlled trials ( RCTs ) in the literature provide an insufficient evidence base to draw reliable conclusions . This study uses a cluster- RCT to add to existing evidence by assessing the impact of a deworming intervention on nutrition , cognition , and school performance among schoolchildren in rural China . The intervention , implemented by local health practitioners in a setting with a baseline infection prevalence of 41.9 % ( 95 % confidence interval [ CI ] = 39.8 % , 43.9 % ) and infection intensity of 599.5 eggs per gram of feces among positive-tested schoolchildren ( 95 % CI = 473.2 , 725.8 ) , consisted of distributing a 400-mg dose of albendazole accompanied with educational training about STH infection , treatment , and prevention . The intervention was conducted twice over the course of the study -at baseline in May 2013 and later in November 2013 . We found that the deworming intervention reduced both infection prevalence and infection intensity , but these declines in infection were not accompanied by an impact on outcomes of nutrition , cognition , or school performance . Our interpretation is that the impact of deworming was attenuated by the light infection intensity in our sample population . Evidence from future RCTs is needed to assess the effect of deworming on key outcomes in areas with moderate and severe worm infections Abstract Background : Documents from advocacy and fund-raising organizations for child mass deworming programmes in low- and middle-income countries cite unpublished economic studies cl aim ing long-term effects on health , schooling and economic development . Methods : To summarize and appraise these studies , we search ed for and included all long-term follow-up studies based on cluster-r and omized trials included in a 2015 Cochrane review on deworming . We used Cochrane methods to assess risk of bias , and appraised the credibility of the main findings . Where necessary we contacted study authors for clarifications . Results : We identified three studies ( Baird 2016 , Ozier 2016 and Croke 2014 ) evaluating effects more than 9 years after cluster-r and omized trials in Kenya and Ug and a. Baird and Croke evaluate short additional exposures to deworming programmes in setting s where all children were dewormed multiple times . Ozier evaluates potential spin-off effects to infants living in areas with school-based deworming . None of the studies used pre-planned protocol s nor blinded the analysis to treatment allocation . Baird 2016 has been presented online in six iterations . The work is at high risk of reporting bias and selective reporting , and there are substantive changes between versions . The main cited effects on secondary school attendance and job sector allocation are from post hoc subgroup analyses , which the study was not powered to assess . The study did not find any evidence of effect on nutritional status , cognitive tests or school grade s achieved , but these are not reported in the abstract s. Ozier 2016 has been presented online in four iterations , without substantive differences between versions . Higher cognitive test scores were associated with deworming , but the appropriate analysis was underpowered to reliably detect these effects . The size of the stated effect seems inconsistent with the short and indirect nature of the exposure to deworming , and a causal pathway for this effect is unclear . Croke 2014 uses a data set unrelated to the base trial , to report improvements in English and maths test scores . The analysis is at high risk of attrition bias , due to loss of clusters , and is substantially underpowered to assess these effects . Conclusions : In the context of reliable epidemiological methods , all three studies are at risk of substantial method ological bias . They therefore help in generating hypotheses , but should not be considered to provide reliable evidence of effects Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample Objective : The study was conducted to assess the effectiveness of six monthly albendazole ( ABZ ) for improving the weight and height of preschool children when initia ted at 0.5–1 year of age in population s with a high transmission rate of intestinal roundworm , Ascaris lumbricoides . It was a cluster r and omized trial in the urban slums of Lucknow , North India . Methods : Control children received 2 ml ( 1 ml to infants ) of Vitamin A every six month whereas those in the ABZ areas received , in addition , 400 mg of ABZ suspension ( Zentel , SKB ) every six month . Sixty-three and sixty-one slum areas were r and omized to albendazole ( ABZ ) or to control groups , respectively . Children aged 0.5–1 year were recruited in April 1996 and followed up for 1.5 years . Of 1022 children recruited from control and 988 from ABZ areas , the loss to follow-up at 1.5 year was 15.6 % and 14.6 % respectively . Mean ( ±SE ) weight gain in Kg in control versus ABZ areas was 3.04 ( 0.03 ) versus 3.22 ( 0.03 ) , ( p=0.01 ) . Results : After controlling for the presence of weight-for age z-score < -2.00 at enrollment in the ordinary least square ’s regression model , the extra weight gain in 1.5 years in those who received ABZ plus vitamin A was 0.13 Kg ( 95 % Cl:0.004 to 0.26 Kg . , p value=0.043 ) when compared to those who received only vitamin A ; underweight children at enrollment benefiting more than the normal ones . Conclusion : It was concluded that there was an improvement in weight with six monthly ABZ over 1.5 years . However , a much larger trial would be needed to determine whether there is any net effect of improvement in weight on under five mortality rate The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children ( age 9–12 years ) in Jamaica , using a double-blind placebo-controlled protocol . Results were evaluated by using a forward-stepwise multiple linear regression . Removal of worms led to a significant improvement in tests of auditory short-term memory ( p < 0.017 ; p < 0.013 ) , and scanning and retrieval of long-term memory ( p < 0.001 ) . Nine weeks after treatment , there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function . It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy The effects of mild to moderate infections of Trichuris trichiura on cognitive functions were investigated in Jamaican children aged 7 to 10 years . In all , 189 infected children and 100 uninfected classmates were studied . The infected children were r and omly assigned to receive treatment ( albendazole ) or a placebo . All children were given cognitive tests on enrolment and 14 weeks later . These included verbal fluency ( generation of ideas ) , digit span ( working memory ) , number choice ( speed of processing of visual stimuli ) , visual search ( sustained attention ) and a French Vocabulary test ( paired-associate learning ) . At baseline , the infected children had lower scores than the uninfected ones in fluency ( P = 0.01 ) , search ( P = 0.02 ) and French ( P = 0.01 ) . Treatment effects were examined among infected children and there was no significant treatment effect for any of the tests . However , there was a significant treatment by weight-for-age interaction in fluency ( P < 0.05 ) . The children with low weight-for-age ( Z-score < -1 ) improved with treatment while there was no improvement with treatment among the other children . We concluded that treatment of children with mild to moderate T. trichiura infections using albendazole produces little benefit in cognition if they are adequately nourished ; however , undernourished children are more likely to benefit OBJECTIVE To determine the prevalence and intensity of intestinal helminth species among school children in southern Ug and a. DESIGN A cross-sectional survey using a r and omly selected sample . SETTING Eighteen districts of southern Ug and a. SUBJECT Two thous and and four school children aged two to twenty years ( 93.3 % , aged 5 - 10 years ) selected from classes 1 and 2 in 26 r and omly selected primary schools . RESULTS Overall , 55.9 % of children were infected with either hookworm , Ascanis lumbricoides or Trichuris trichiura . The prevalence of A. lumbricoides was 17.5 % ( range 0 - 66.7 % by school ) , T. trichiura was 7.3 % ( 0 - 45.0 % ) and hookworm 44.5 % ( 15.6 - 86.0 % ) . The prevalence of A. lumbricoides and T. trichiura was greatest in western districts while hookworm infection was more evenly distributed across the country . CONCLUSION Mass antihelminthic treatment of school children was warranted in 13 of the 18 districts as more than 50 % of the children were infected with an intestinal nematode . It is likely that pre-school children are similarly infected Abstract Objective To estimate the effectiveness of delivering an anthelmintic through a community child health programme on the weight gain of preschool children in Ug and a. Design Cluster r and omised controlled trial . Setting Eastern Ug and a. Participants 48 parishes participating in a new programme for child health : 24 offered children an additional service of anthelmintic treatment . The outcome is based on measurements from 27 995 children . Intervention Treatment of children aged between 1 and 7 years with 400 mg albendazole added to st and ard services offered during child health days over a three year period . Main outcome measure Weight gain . Results The provision of periodic anthelmintic treatment as a part of child health services in Ug and a result ed in an increase in weight gain of about 10 % ( 166 g per child per year , 95 % confidence interval 16 to 316 ) above expected weight gain when treatments were given twice a year , and an increase of 5 % when the treatment was given annually . Conclusion Deworming of preschool children in Ug and a as part of regularly scheduled health services seems practical and associated with increased weight gain |
514 | 31,321,710 | In fact , the observed results partially in contrast with those of numerous r and omized controlled trials have documented a significant BP reduction combined with an intensification and optimization of the use of antihypertensive medications in patients making use of blood pressure telemonitoring plus remote counseling by a case manager , with the supervision of a doctor or a community pharmacist [ 5 , 6 ] . | Despite the availability of a large number of effective and relatively safe antihypertensive drugs , the control of hypertension in general population is suboptimal , reaching the 70 % in the best practice setting s. In particular , despite its economic power , Europe also ranges among the regions with the lowest rates of hypertension awareness and control worldwide [ 1 ] .
On the one h and , this predominance reflects the increasing life expectancy in European population , whereas on the other h and , it can be attributed to the sedentary lifestyle and the nutritional habits of wealthy societies , but also to medical inertia , insufficient patient education and contradictory recommendations from different institutions and scientific societies [ 2 ] .
In this context , the comparative evaluation of the effectiveness of different tools to improve hypertension control is of great interest , especially if the cost of the intervention is also estimated .
This raises a serious issue , as health professionals and those with hypertension have insufficient information to make decisions on which apps are safe and effective . | Question In patients with hypertension , do electronic health ( e-health ) interventions improve blood pressure ( BP ) control and other outcomes ? Review scope Included studies compared e-health interventions with usual or st and ard care or attention control in patients with adequately or inadequately controlled hypertension . E-health interventions had to use portable , Web-based , interactive wireless communication devices and focus on self-care , self-management , self-care behavior change , or education . Studies of interventions that only displayed information ( not interactive ) , were only used for follow-up , or that mostly benefitted health care providers were excluded . Outcomes included physical outcomes ( inadequate BP control , systolic [ SBP ] and diastolic BP [ DBP ] , body mass index [ BMI ] , body weight , and cholesterol levels ) , and self-care behavioral outcomes ( sodium and alcohol intake , smoking , and physical activities ) . Review methods MEDLINE , EMBASE /Excerpta Medica , Cochrane Data base of Systematic Review s , Cochrane Central Register of Controlled Trials , CINAHL Plus , PsycINFO , SCOPUS , Web of Science , Joanna Briggs Institute EBP Data base , INSPEC , China Journal Net , and WanFang Data ( all 2000 to Nov 2017 ) were search ed for English- and Chinese- language r and omized controlled trials ( RCTs ) . 14 RCTs ( n = 3998 , mean age 50 to 68 y ) , ranging in size from 44 to 778 patients , met the selection criteria . Follow-up ranged from 3 to 24 months . Studies were conducted in various setting s , including primary care clinics , community health centers , and hospitals . Intervention strategies included BP monitoring , lifestyle modification techniques , and motivation and maintenance . 9 RCTs had adequate r and omization sequence generation , 6 concealed allocation , 4 blinded outcome assessors , and none adequately reported blinding participants . Main results Results for inadequate BP control , SPB , DBP , BMI , body weight , and sodium intake are in the Table . E-health interventions did not improve total cholesterol levels at 3 to 6 months after the intervention ( 3 RCTs ) ; or alcohol intake , smoking , or physical activity at 6 months after the intervention ( 3 RCTs ) . Conclusion In patients with hypertension , electronic health interventions reduce blood pressure levels and increase likelihood of blood pressure control . Electronic health interventions vs control in patients with hypertension * Outcomes Assessment times ( after intervention ) Number of trials ( n ) RRR ( 95 % CI ) NNT ( CI ) Inadequate BP control 3 to 12 mo 5 ( 1518 ) 31 % ( 16 to 43 ) 6 ( 4 to 11 ) Mean between-group difference ( CI ) Change in systolic BP ( mm Hg ) 6 mo 12 ( 3171 ) 5.50 ( 9.85 to 1.16 ) 12 mo 3 ( 1272 ) 7.68 ( 9.95 to 5.41 ) 18 mo 2 ( 735 ) 6.26 ( 9.29 to 3.23 ) Change in diastolic BP ( mm Hg ) 6 mo 12 ( 3171 ) 3.40 ( 7.79 to 0.99 ) 12 mo 3 ( 1272 ) 3.36 ( 4.80 to 1.92 ) 18 mo 2 ( 735 ) 2.53 ( 4.72 to 0.34 ) Change in body mass index ( kg/m2 ) 6 mo 5 ( 1486 ) 0.22 ( 0.46 to 0.02 ) 12 mo 3 ( 1272 ) 0.24 ( 0.82 to 0.33 ) 18 mo 2 ( 735 ) 0.07 ( 0.77 to 0.91 ) Change in body weight ( kg ) 3 to 6 mo 3 ( 517 ) 1.08 ( 2.04 to 0.13 ) Change in sodium intake ( SMD ) 6 mo 2 ( 768 ) 0.34 ( 0.49 to 0.20 ) 12 mo 2 ( 753 ) 0.39 ( 0.54 to 0.25 ) 18 mo 2 ( 735 ) 0.30 ( 0.45 to 0.16 ) * BP = blood pressure ; SMD = st and ardized mean difference ; other abbreviations defined in Glossary . Weighted electronic health intervention event rate , RRR , NNT , and CI calculated using control event rate and relative risk in article . Blood pressure 140/90 mm Hg . Weighted event rates 42 % vs 60 % . Commentary The systematic review and meta- analysis by Ma and colleagues showed a small but clinical ly meaningful reduction in SBP and DBP in patients who received e-health re sources . However , some health outcomes , including BMI and cholesterol levels , were not improved . Despite a risk for selection bias in some of the studies and substantial heterogeneity between studies , the meta- analysis is of high quality . The interventions in the included studies varied greatly and included use of telephone calls , Web sites , and smartphone applications . The comparison treatments were either attention control or usual care , and trials did not directly compare e-health interventions . The outcomes measured also varied among studies . Because clinic BP measurements may overestimate the degree of elevation and ambulatory monitoring is costly and limited to brief periods of measurement , home BP monitoring using newer e-health re sources may provide a cost-effective alternative ( 1 ) . This is an exciting new avenue for improving BP control by allowing for more accurate and streamlined monitoring , leading to more precise and timely interventions . However , based on the heterogeneity of intervention types , the optimum method is unknown . Further studies should directly compare e-health platforms and assess patient-centered outcomes , including usability , satisfaction , affordability , and quality of life as well as BP . Although the evidence indicates that these interventions are not yet ready for routine clinical practice , there is a promising signal that they could be useful for BP management Self-management schemes and mobile apps can be used for the management of hypertension in the community , but the most appropriate patient population is unknown . To explore whether the Chinese Health Literacy Scale ( CHLSH ) can be used to screen for appropriate patients with hypertension for self-management and to evaluate the clinical effectiveness and health economic evaluation of three hypertension management schemes . This was a prospect i ve study performed from March 2017 to July 2017 in consecutive patients with primary hypertension and of 50–80 years of age from the Jinyang community , Wuhou District , Chengdu . The CHLSH was completed and the patients were classified into the high ( n = 283 ) and low ( n = 315 ) health literacy groups . The patients were r and omly divided into the self-management , traditional management , and mobile app management groups . The high-health literacy group was selected to construct the cost-effectiveness decision tree model . Blood pressure control rate and the quality -adjusted life years ( QALYs ) were determined . At the end of follow-up , the success rate of self-management was 83.4 % . The costs for 6 months of treatment for each patient with hypertension in the self-management , traditional management , and mobile app groups were 1266 , 1751 , and 1856 yuan , respectively . The costs required for obtaining 1 QALY when managing for 6 months were : 30,869 yuan for self-management ; 48,628 yuan for traditional management ; and 43,199 yuan for the mobile app . The CHLSH can be used as a tool for screening patients with hypertension for self-management . The cost-effectiveness of self-management was optimal |
515 | 24,297,482 | There was no good evidence that the addition of a non-monetary incentive , an offer of a non-monetary incentive , ' enhanced ' letters , letters delivered by priority post , additional reminders , or question naire question order either increased or decreased trial question naire response/retention .
There were few evaluations of ways to improve participants returning to trial sites for trial follow-up .
Monetary incentives and offers of monetary incentives increased postal and electronic question naire response .
Key results The methods that appeared to work were offering or giving a small amount of money for return of a completed question naire and enclosing a small amount of money with a question naire with the promise of a further small amount of money for return of a filled in question naire . | Background Loss to follow-up from r and omised trials can introduce bias and reduce study power , affecting the generalisability , validity and reliability of results .
Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated .
Objectives To quantify the effect of strategies to improve retention on the proportion of participants retained in r and omised trials and to investigate if the effect varied by trial strategy and trial setting .
There are many ways to collect data from people in trials , and these include using letters , the internet , telephone calls , text messaging , face-to-face meetings or the return of medical test kits .
Most trials have missing data , for example , because people are too busy to reply , are unable to attend a clinic , have moved or no longer want to participate .
Sometimes data has not been recorded at study sites , or are not sent to the trial co-ordinating centre .
Research ers call this ' loss to follow-up ' , ' drop out ' or ' attrition ' and it can affect the trial 's results .
For example , if the people with the most or least severe symptoms do not return question naires or attend a follow-up visit , this will bias the findings of the trial .
Many methods are used by research ers to keep people in trials .
These encourage people to send back data by question naire , return to a clinic or hospital for trial-related tests , or be seen by a health or community care worker . | Given that retention rates for weight-loss trials have not significantly improved in the past 20 years , identifying effective techniques to enhance retention is critical . This paper describes a conceptual and practical advance that may have improved retention in a behavioral weight-loss trial-the novel application of motivational interviewing techniques to diffuse ambivalence during interactive group-based orientation sessions prior to r and omization . These orientation sessions addressed ambivalence about making eating and exercise behavior changes , ambivalence about joining a r and omized controlled trial , and unrealistic weight-loss expectations . During these sessions , overweight and obese men and women learned about the health benefits of modest weight loss as well as trial design , the importance of a control condition , r and om assignment and the impact of dropouts . Participants were then divided into groups of three or four , and asked to generate two pros and two cons of being assigned to a control condition and an active condition . Participants shared their pros and cons with the larger group , while the investigator asked open-ended questions , engaged in reflective listening and avoided taking a ' pro-change ' position . Retention was high , with 96 % of the participants ( N = 162 ) completing 18-month clinic visits Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months This study examined the role of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance within a r and omized trial of bupropion-SR for smoking cessation . Female participants ( N = 97 ) received MEMS bottles containing bupropion-SR 150 mg or placebo , to be taken twice daily . A r and omly selected “ feedback ” group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance . A “ no-feedback ” group was not informed about the MEMS bottles , and did not receive further instruction or feedback beyond the st and ard dosing instructions . Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the feedback group . Participation in the feedback group predicted higher compliance beyond demographic , smoking , and health belief variables , suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions OBJECTIVE To determine the effect of a voucher for free mammography on compliance with recommended mammography screening guidelines . STUDY DESIGN Vouchers for free mammography distributed to a r and om sample of women over the age of 50 in two rural southern Minnesota counties . The vouchers were good for one year . Baseline and follow-up data were collected and rates of compliance with current mammography guidelines were observed for the voucher group and a control group of women living in the same counties . METHODS Logistic regression models were used to estimate the effect of the voucher on compliance with mammography guidelines and the impact of factors potentially influencing the effectiveness of the voucher . PRINCIPAL FINDINGS The voucher improved mammography rates primarily through increasing screening among women who were out of compliance at baseline . CONCLUSIONS Vouchers , even when distributed r and omly within a population of rural Midwestern women , can significantly improve compliance rates . Vouchers are no less effective a means of increasing screening among vulnerable women than among other women Background Postal question naires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results . There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting . Methods The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers ' joined the MRC ORACLE Trial . We carried out a r and omised controlled trial of inclusion of monetary incentive ( five pound voucher redeemable at many high street stores ) with the reminder question naire to parents . This trial took place between April 2002 and November 2003 . When the parents were sent the reminder question naire about their child 's health and development they were r and omly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive . The population were 722 non-responders to the initial mailing of a 12-page question naire . Main outcome measures : Difference in response rate between the two groups . Results Inclusion of the voucher with the reminder question naire result ed in a 11.7%(95 % CI 4.7 % to 18.6 % ) improvement in the response rate between the two groups . Conclusion This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially OBJECTIVE To test the efficacy of a prevention intervention to reduce sexual risk behavior among Latino adolescents . DESIGN R and omized controlled trial from April 2000 through March 2003 , with data collection before and after intervention and at 3 , 6 , and 12 months . SETTING Northeast Philadelphia schools . PARTICIPANTS Latinos aged 13 through 18 years ( 249 males and 304 females ) ; 81.6 % retained at 12-month follow-up . INTERVENTIONS The HIV and health-promotion control interventions consisted of six 50-minute modules delivered by adult facilitators to small , mixed-gender groups in English or Spanish . Main Outcome Measure Self-reported sexual behavior . RESULTS Analyses using generalized estimation equations over the follow-up period revealed that adolescents in the HIV intervention were less likely to report sexual intercourse ( odds ratio , 0.66 ; 95 % confidence interval [ CI ] , 0.46 - 0.96 ) , multiple partners ( odds ratio , 0.53 ; 95 % CI , 0.31 - 0.90 ) , and days of unprotected intercourse ( relative risk , 0.47 ; 95 % CI , 0.26 - 0.84 ) and more likely to report using condoms consistently ( odds ratio , 1.91 ; 95 % CI , 1.24 - 2.93 ) . Baseline sexual experience and language use moderated intervention efficacy . Adolescents assigned to the HIV intervention who were sexually inexperienced at baseline reported fewer days of unprotected sex ( relative risk , 0.22 ; 95 % CI , 0.08 - 0.63 ) ; Spanish speakers were more likely to have used a condom at last intercourse ( odds ratio , 4.73 ; 95 % CI , 1.72 - 12.97 ) and had a greater proportion of protected sex ( mean difference , 0.35 ; P<.01 ) compared with similar adolescents in the health-promotion intervention . CONCLUSION Results provide evidence for the efficacy of HIV intervention in decreasing sexual activity and increasing condom use among Latino adolescents Background It is notoriously difficult to recruit patients to r and omised controlled trials in primary care . This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window . Bell 's palsy , an acute unilateral paralysis of the facial nerve is just such a relatively rare condition . In this case study we describe the organisational issues presented in setting up a large r and omised controlled trial of the management of Bell 's palsy across primary and secondary care in Scotl and and how we managed to successfully recruit and retain patients presenting in the community . Methods Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention . We consider that the key issues in the success of this study were ; the fact that the research was seen as clinical ly important by the clinicians who had initial responsibility for recruitment ; employing an experienced trial co-ordinator and dedicated research ers willing to recruit participants seven days per week and to visit them at home at a time convenient to them , hence reducing missed patients and ensuring they were retained in the study ; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community ; encouraging recruitment by payment to practice s and reducing the workload of the referring doctors by providing immediate access to specialist care ; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Results Although the recruitment rate did not meet our initial expectations , enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale . Conclusion While difficult , recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence , establishing good relationships with practice s , minimising the workload of those involved in recruitment and offering enhanced care to all participants . Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results STUDY OBJECTIVE For orthopaedic out patients judged as unlikely to require surgery , how does the cost-effectiveness of treatment from a musculo-skeletal medicine physician compare with that of a conventional orthopaedic surgeon-led service ? DESIGN Partially r and omised , pragmatic trial comparing management from a single musculo-skeletal medicine physician with orthopaedic surgeon-led management , with the timing and nature of treatments at the discretion of individual clinicians . Main outcomes were : change in patient reported health ( SF-36 and EuroQol ) , and marginal health service costs . SETTING Outpatient department of an Edinburgh orthopaedic hospital . SUBJECTS One thous and three hundred and twenty six people ; aged over 18 , referred to and later attending the outpatient department with a ' non-surgical ' musculo-skeletal condition , who provided baseline information . Eight hundred and twenty nine were r and omly allocated to management by either the musculo-skeletal medicine physician ( medical group ) or a conventional orthopaedic surgeon-led service ( surgical group ) ; 497 were assigned to the treatment groups according to their general practitioner 's preference . RESULTS There are aspects of the study design concerning statistical power , potential selection bias and generalisability , which mean that any results must be treated with caution . Although there was no statistically significant difference in health gain between the r and omly allocated groups ( with similar findings in the non-r and omised medical and surgical groups ) , the patient groups were heterogeneous and the confidence intervals did not rule out clinical ly important differences . The medical group received more outpatient treatment , 20 % vs. 10 % ( difference 95 % CI 5 % to 15 % ) with a higher rate of physiotherapy referral , 45 % vs. 30 % ( 15 % , 9 % to 22 % ) . The surgical group received more inpatient surgical care 6 % vs. 17 % ( -11 % , -15 % to -7 % ) . Mean healthcare costs in the medical group were 179 Pounds per patient compared with 287 Pounds in the surgical group ( -108 Pounds , -25 Pounds to -191 Pounds ) . CONCLUSIONS Interpretation should take into account the practical difficulties and circumstances of the study . Although no differences in health gain were found between these two management policies for ' non-surgical ' orthopaedic out patients , the trial was less statistically powerful than planned and the confidence intervals included clinical ly important differences . Differences in treatment emphasis gave estimated costs savings to the Health Service of 108 Pounds per patient treated by the musculo-skeletal medicine service A motivational orientation intervention design ed to improve parenting program retention was field tested versus st and ard orientation across two parenting programs , Parent — Child Interaction Therapy ( PCIT ) and a st and ard didactic parent training group . Both interventions were implemented within a frontline child welfare parenting center by center staff . Participants had an average of six prior child welfare referrals , primarily for neglect . A double-r and omized design was used to test main and interaction effects . The motivational intervention improved retention only when combined with PCIT ( cumulative survival = 85 % vs. around 61 % for the three other design cells ) . Benefits were robust across demographic characteristics and participation barriers but were concentrated among participants whose initial level of motivation was low to moderate . There were negative effects for participants with relatively high initial motivation . The findings suggest that using a motivational intervention combined with PCIT can improve retention when used selectively with relatively low to moderately motivated child welfare clients Abstract Objective : To compare three different methods of administering a brief screening question naire to elderly people : post , interview by lay interviewer , and interview by nurse . Design : R and omised comparison of methods within a cluster r and omised trial . Setting : 106 general practice s in the United Kingdom . Participants : 32 990 people aged 75 years or over registered with participating practice s. Main outcome measures : Response rates , proportion of missing values , prevalence of self reported morbidity , and sensitivity and specificity of self reported measures by method of administration of question naire for four domains . Results : The response rate was higher for the postal question naire than for the two interview methods combined ( 83.5 % v 74.9 % ; difference 8.5 % , 95 % confidence interval 4.4 % to 12.7 % , P<0.001 ) . The proportion of missing or invalid responses was low overall ( mean 2.1 % ) but was greater for the postal method than for the interview methods combined ( 4.1 % v 0.9 % ; difference 3.2 % , 2.7 % to 3.6 % , P<0.001 ) . With a few exceptions , levels of self reported morbidity were lower in the interview groups , particularly for interviews by nurses . The sensitivity of the self reported measures was lower in the nurse interview group for three out of four domains , but 95 % confidence intervals for the estimates overlapped . Specificity of the self reported measures varied little by method of administration . Conclusions : Postal question naires were associated with higher response rates but also higher proportions of missing values than were interview methods . Lower estimates of self reported morbidity were obtained with the nurse interview method and to a lesser extent with the lay interview method than with postal question naires . What is already known on this topic The optimum method of administering a brief multidimensional screening assessment to elderly people is not known What this study adds Postal question naires produce a higher response rate than interviews by nurses or lay interviewers but also higher proportions of missing data Interview by nurses and to a lesser degree by lay interviewers is associated with lower levels of self reported morbidity than are postal question Background Sending a monetary incentive with postal question naires has been found to improve the proportion of responders , in research in non-healthcare setting s. However , there is little research on use of incentives to improve follow-up rates in clinical trials , and existing studies are inconclusive . We conducted a r and omised trial among participants in the Managing Injuries of the Neck Trial ( MINT ) to investigate the effects on the proportion of question naires returned and overall non-response of sending a £ 5 gift voucher with a follow-up question naire . Methods Participants in MINT were r and omised to receive either : ( a ) a £ 5 gift voucher ( incentive group ) or ( b ) no gift voucher ( no incentive group ) , with their 4 month or 8 month follow-up question naire . We recorded , for each group , the number of question naires returned , the number returned without any chasing from the study office , the overall number of non-responders ( after all chasing efforts by the study office ) , and the costs of following up each group . Results 2144 participants were r and omised , 1070 to the incentive group and 1074 to the no incentive group . The proportion of question naires returned ( RR 1.10 ( 95 % CI 1.05 , 1.16 ) ) and the proportion returned without chasing ( RR 1.14 ( 95 % CI 1.05 , 1.24 ) were higher in the incentive group , and the overall non-response rate was lower ( RR 0.68 ( 95 % CI 0.53 , 0.87 ) ) . Adjustment for injury severity and hospital of recruitment to MINT made no difference to these results , and there were no differences in results between the 4-month and 8-month follow up question naires . Analysis of costs suggested a cost of £ 67.29 per additional question naire returned . Conclusion Monetary incentives may be an effective way to increase the proportion of postal question naires returned and minimise loss to follow-up in clinical trials . Trial registration numberIS RCT Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation ( COMMIT ) . One outcome measurement , the quit rate in r and omly selected cohorts of smokers , is compared with another outcome measurement , the decrease in smoking prevalence , in terms of statistical efficiency and interpretability . The COMMIT study uses both types of outcome measurements . The merits of pair-matching the communities are considered , and sample size calculations take into account heterogeneity among pair-matched communities . In addition to significance tests based on the permutational ( r and omization ) distribution , we also describe approaches for covariate adjustment . The COMMIT design includes 11 pair-matched communities , which should provide good power to detect a 10 % or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers . The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking PURPOSE The purpose of this article was to describe effective recruitment and retention strategies used in a community-based intervention study for older , rural African American women with type 2 diabetes . METHODS The study 's design was a r and omized control test using a 3-group experimental design in a sample of 180 older , rural African American women ( 55 years of age and older ) , with type 2 diabetes . The study employed a range of strategies to successfully recruit and retain older African American women . These strategies were initially developed based on a review of the literature and the investigators ' prior experience . They were modified as the research progressed . RESULTS More than a quarter of the participants were recruited from outpatient clinics . In-person outreach to health care providers was essential to engage and retain their help in recruiting patients . The research team made it easy and rewarding for women to participate in the study by providing a toll-free phone number , culturally appropriate intervention material s , intervention in the home , and incentives . Developing a relationship of trust with participants and the community was critical throughout the study period . Through the use of these strategies , the target enrollment of 180 women was met with 91 % retention rate at the completion of the study . CONCLUSION The use of multiple strategies can enhance recruitment and retention of rural , older African American women into a research study . Strategies are most effective when they build a relationship of trust with participants and the community and make it easy and rewarding for women to participate The objectives of the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55 - 74 at entry whether screening with flexible sigmoidoscopy ( 60-cm sigmoidoscope ) can reduce mortality from colorectal cancer , whether screening with chest X-ray can reduce mortality from lung cancer , whether screening men with digital rectal examination ( DRE ) plus serum prostate-specific antigen ( PSA ) can reduce mortality from prostate cancer , and whether screening women with CA125 and transvaginal ultrasound ( TVU ) can reduce mortality from ovarian cancer . Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity , specificity , and positive predictive value ; to assess incidence , stage , and survival of cancer cases ; and to investigate biologic and /or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints . The design is a multicenter , two-armed , r and omized trial with 37,000 females and 37,000 males in each of the two arms . In the intervention arm , the PSA and CA125 tests are performed at entry , then annually for 5 years . The DRE , TVU , and chest X-ray exams are performed at entry and then annually for 3 years . Sigmoidoscopy is performed at entry and then at the 5-year point . Participants in the control arm follow their usual medical care practice s. Participants will be followed for at least 13 years from r and omization to ascertain all cancers of the prostate , lung , colorectum , and ovary , as well as deaths from all causes . A pilot phase was undertaken to assess the r and omization , screening , and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels . This paper describes eligibility , consent , and other design features of the trial , r and omization and screening procedures , and an outline of the follow-up procedures . Sample -size calculations are reported , and a data analysis plan is presented Abstract Objective To assess the cost effectiveness of adding spinal manipulation , exercise classes , or manipulation followed by exercise ( “ combined treatment ” ) to “ best care ” in general practice for patients consulting with low back pain . Design Stochastic cost utility analysis alongside pragmatic r and omised trial with factorial design . Setting 181 general practice s and 63 community setting s for physical treatments around 14 centres across the United Kingdom . Participants 1287 ( 96 % ) of 1334 trial participants . Main outcome measures Healthcare costs , quality adjusted life years ( QALYs ) , and cost per QALY over 12 months . Results Over one year , mean treatment costs relative to “ best care ” were £ 195 ( $ 360 ; € 279 ; 95 % credibility interval £ 85 to £ 308 ) for manipulation , £ 140 ( £ 3 to £ 278 ) for exercise , and £ 125 ( £ 21 to £ 228 ) for combined treatment . All three active treatments increased participants ' average QALYs compared with best care alone . Each extra QALY that combined treatment yielded relative to best care cost £ 3800 ; in economic terms it had an “ incremental cost effectiveness ratio ” of £ 3800 . Manipulation alone had a ratio of £ 8700 relative to combined treatment . If the NHS was prepared to pay at least £ 10 000 for each extra QALY ( lower than previous recommendations in the United Kingdom ) , manipulation alone would probably be the best strategy . If manipulation was not available , exercise would have an incremental cost effectiveness ratio of £ 8300 relative to best care . Conclusions Spinal manipulation is a cost effective addition to “ best care ” for back pain in general practice . Manipulation alone probably gives better value for money than manipulation followed by exercise BACKGROUND Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures . Several newer drugs possess efficacy against these seizure types but previous r and omised controlled trials have failed to inform a choice between these drugs . We aim ed to assess efficacy with regards to longer-term outcomes , quality of life , and health economic outcomes . METHODS SANAD was an unblinded r and omised controlled trial in hospital-based outpatient clinics in the UK . Arm A recruited 1721 patients for whom carbamazepine was deemed to be st and ard treatment , and they were r and omly assigned to receive carbamazepine , gabapentin , lamotrigine , oxcarbazepine , or topiramate . Primary outcomes were time to treatment failure , and time to 12-months remission , and assessment was by both intention to treat and per protocol . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N38354748 . FINDINGS For time to treatment failure , lamotrigine was significantly better than carbamazepine ( hazard ratio [ HR ] 0.78 [ 95 % CI 0.63 - 0.97 ] ) , gabapentin ( 0.65 [ 0.52 - 0.80 ] ) , and topiramate ( 0.64 [ 0.52 - 0.79 ] ) , and had a non-significant advantage compared with oxcarbazepine ( 1.15 [ 0.86 - 1.54 ] ) . For time to 12-month remission carbamazepine was significantly better than gabapentin ( 0.75 [ 0.63 - 0.90 ] ) , and estimates suggest a non-significant advantage for carbamazepine against lamotrigine ( 0.91 [ 0.77 - 1.09 ] ) , topiramate ( 0.86 [ 0.72 - 1.03 ] ) , and oxcarbazepine ( 0.92 [ 0.73 - 1.18 ] ) . In a per- protocol analysis , at 2 and 4 years the difference ( 95 % CI ) in the proportion achieving a 12-month remission ( lamotrigine-carbamazepine ) is 0 (-8 to 7 ) and 5 ( -3 to 12 ) , suggesting non-inferiority of lamotrigine compared with carbamazepine . INTERPRETATION Lamotrigine is clinical ly better than carbamazepine , the st and ard drug treatment , for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures Background There has been limited study of factors influencing response rates and attrition in online research . Online experiments were nested within the pilot ( study 1 , n = 3780 ) and main trial ( study 2 , n = 2667 ) phases of an evaluation of a Web-based intervention for hazardous drinkers : the Down Your Drink r and omized controlled trial ( DYD- RCT ) . Objectives The objective was to determine whether differences in the length and relevance of question naires can impact upon loss to follow-up in online trials . Methods A r and omized controlled trial design was used . All participants who consented to enter DYD- RCT and completed the primary outcome question naires were r and omized to complete one of four secondary outcome question naires at baseline and at follow-up . These question naires varied in length ( additional 23 or 34 versus 10 items ) and relevance ( alcohol problems versus mental health ) . The outcome measure was the proportion of participants who completed follow-up at each of two follow-up intervals : study 1 after 1 and 3 months and study 2 after 3 and 12 months . Results At all four follow-up intervals there were no significant effects of additional question naire length on follow-up . R and omization to the less relevant question naire result ed in significantly lower rates of follow-up in two of the four assessment s made ( absolute difference of 4 % , 95 % confidence interval [ CI ] 0%-8 % , in both study 1 after 1 month and in study 2 after 12 months ) . A post hoc pooled analysis across all four follow-up intervals found this effect of marginal statistical significance ( unadjusted difference , 3 % , range 1%-5 % , P = .01 ; difference adjusted for prespecified covariates , 3 % , range 0%-5 % , P = .05 ) . Conclusions Apparently minor differences in study design decisions may have a measurable impact on attrition in trials . Further investigation is warranted of the impact of the relevance of outcome measures on follow-up rates and , more broadly , of the consequences of what we ask participants to do when we invite them to take part in research studies . Trial registration IS RCT N Register 31070347 ; http://www.controlled-trials.com/IS RCT N31070347/31070347 Archived by WebCite at ( http://www.webcitation.org/62cpeyYaY The purpose s of this article are : ( a ) to describe and analyze the accrual and retention patterns in a longitudinal r and omized clinical trial with prostate cancer patients and their partners , and ( b ) to discuss strategies that were used to overcome challenges in conducting this family-based study . Initially , 429 dyads were referred to the study . Of these , 166 were not enrolled due to refusal ( n = 120 ) or in eligibility ( n = 46 ) , 21 of whom did not meet one or more of the inclusion criteria , and 25 of whom could not be reached within the 2-month window of eligibility . Of the 383 eligible dyads , 263 dyads were enrolled ( enrollment rate of 68.7 % ) . Accrual and retention patterns differed by research site , referral procedures , and phase of prostate cancer . The retention rate was very good with the majority of dyads ( n = 218 ) completing all three follow-up assessment s at 4 , 8 , and 12 months ( 82.9 % ) BACKGROUND A range of factors have been shown to affect the response rate to mailed question naires , but particular strategies to improve patients ' response in trials conducted in general practice require further study . METHODS Non-responders in a larger trial were r and omized to receive a telephone or recorded delivery reminder on the third contact . The cost of administration of each method was estimated . RESULTS Significantly more patients returned completed question naires when sent question naires by recorded delivery , although the cost per patient contacted was nearly three times more than for contact by telephone . CONCLUSION Our study indicates that sending reminders by recorded delivery , although more expensive , is more effective than telephone reminders for recruiting patients to a study in general practice using research question naires In this study , the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency question naires ( FFQs ) : the newly developed 36-page Diet History Question naire ( DHQ ) , design ed to be cognitively easier for respondents , and a 16-page FFQ developed earlier for the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . The PLCO Trial is a 23-year r and omized controlled clinical trial begun in 1992 . The sample for this sub study , which was conducted from January to April of 1998 , consisted of 900 control and 450 screened PLCO participants aged 55 - 74 years . Controls received either the DHQ or the PLCO FFQ by mail . Screenees , who had previously completed the PLCO FFQ at baseline , were administered the DHQ . Among controls , the response rate for both FFQs was 82 % . Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes , respectively . Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower ( p < or = 0.001 ) in the DHQ for questions on portion size and use of vitamin/mineral supplements , respectively . Among screenees , response rates for the DHQ and the PLCO FFQ were 84 % and 89 % , respectively , and analyses of questions on portion size and supplement use showed few differences . These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality , and that clarity and ease of administration may compensate for question naire length Background Loss to follow-up of trial participants represents a threat to research validity . To date , interventions design ed to increase participants ’ awareness of benefits to society of completing follow-up , and the impact of a telephone call from a senior female clinician and research er requesting follow-up have not been evaluated robustly . Purpose Trial 1 aim ed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society . Trial 2 aim ed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and research er . Methods Two single-blind r and omized controlled trials were nested within a larger trial , Txt2stop . In Trial 1 , participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up , or to a control group receiving a simple reminder regarding follow-up . In Trial 2 , participants were r and omly allocated to receive a telephone call from a senior female clinician and research er , or to a control group receiving st and ard Txt2stop follow-up procedures . Results Trial 1 : 33.5 % ( 327 of 976 ) of the intervention group and 33.8 % ( 329 of 974 ) of the control group returned the question naire within 26 weeks of r and omization , risk ratio ( RR ) 0.99 ; 95 % confidence interval ( CI ) 0.88–1.12 . In all , 83.3 % ( 813 of 976 ) of the intervention group and 82.2 % ( 801 of/974 ) of the control group sent back the question naire within 30 weeks of r and omization , RR 1.01 ; 95 % CI 0.97 , 1.05 . Trial 2 : 31 % ( 20 of 65 ) of the intervention group and 32 % ( 20 of 62 ) of the control group completed trial follow-up , RR 0.93 ; 95%CI 0.44 , 1.98 . Conclusions In presence of other methods to increase follow-up neither experimental method ( refrigerator magnet and text message emphasizing participation 's benefits to society nor a telephone call from study 's principal investigator ) increased participant follow-up in the Txt2stop trial OBJECTIVE To estimate the clinical effectiveness and cost-effectiveness of three methods of ankle support compared with double layer tubular compression b and age . DESIGN A r and omised controlled trial , design ed to reflect practice in UK hospital emergency departments . SETTING Eight emergency departments in Engl and . PARTICIPANTS Aged 16 or over with acute severe ankle sprain , unable to weight bear , no fracture . INTERVENTIONS 584 participants were r and omised to one of four treatment arms : tubular b and age , below knee cast , Aircast ankle brace or Bledsoe boot , all applied 2 - 3 days after presentation to allow swelling to resolve . MAIN OUTCOME MEASURES Response to treatment was assessed using the Foot and Ankle Outcome Score and generic measures ( Functional Limitations Profile , SF-12 and EQ-5D ) . RESULTS When adjusted for age , sex and baseline scores , the below knee cast offered a small but statistically significant benefit at 4 weeks in terms of pain ( FAOS pain difference 5.1 ; 95 % CI 0.4 - 9.8 ) , foot- and ankle-related quality of life ( QoL ) ( FAOS QoL difference 5.9 ; 95 % CI 0.1 - 11.8 ) and the physical component of the SF-12 ( SF-12 score difference 2.2 ; 95 % CI 0.0 - 4.4 ) . Neither the Aircast brace nor the Bledsoe boot was statistically or clinical ly better . At 12 weeks the below knee cast was significantly better than tubular b and age in terms of pain ( FAOS pain difference 5.1 ; 95 % CI 0.3 - 10.0 ) , activities of daily living ( FAOS ADL difference 3.5 ; 95 % CI 0.4 - 6.6 ) , sports ( FAOS sports difference 8.7 ; 95 % CI 1.6 - 15.7 ) and QoL ( FAOS QoL difference 8.7 ; 95 % CI 2.4 - 15.0 ) , and the Aircast brace was better only in terms of ankle-related QoL and mental health . The Bledsoe boot conferred no significant advantage over tubular b and age . By 9 months there were no significant differences . Based on mean direct health-care costs per participant , the Bledsoe boot was the most expensive ( 215 pounds ) and tubular b and age the least so ( 1 pound 44 pence ) . Inclusion of indirect costs ( sick leave ) raised overall costs substantially and removed any significant differences between the therapies . Cost-utility analysis demonstrated that the Aircast brace [ 301 pounds per quality -adjusted life-year ( QALY ) ] and below knee cast ( 339 pounds per QALY ) were more cost-effective than the Bledsoe boot ( 2116 pounds per QALY ) . However , inclusion of indirect costs produced different rank orders , depending on the assumptions made , and results should be treated with caution . CONCLUSIONS The below knee cast and the Aircast brace offered cost-effective alternatives to tubular b and age for acute severe ankle sprain , the former having the advantage in terms of overall recovery at 3 months . As there were no differences in long-term outcome , practitioners should consider likely compliance and acceptability to patients when choosing a brace Cocaine dependence has proved difficult to treat , whether occurring alone or in combination with opiate dependence . No medication has been demonstrated to be uniquely effective . Fluoxetine was examined as a c and i date in two r and omized , double-blind , placebo-controlled trials , one with cocaine-dependent patients ( study 1 ) and the other with patients both cocaine and opiate dependent ( study 2 ) . It was selected for known specific action , antidepressant effects , minimum side effects , and data showing reduced cocaine effect and self-administration . Clinic visit frequency requirement , a variable with implication s for treatment and cost , was also examined in study 1 . A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures . Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence ( study 1 ) or opiate and cocaine dependence ( study 2 ) were excluded . Study 1 patients were assigned to one of two visit frequency schedules ( 2 or 5 days/week ) and one of three medication doses ( 0 , 20 , or 40 mg of fluoxetine/day ) . Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week . All patients participated in individual therapy sessions . Urine screens were conducted twice weekly . A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo , 20 mg , and 40 mg . Dose effect order was the same for both visit conditions . Cocaine use persisted in all groups . The two visits/week condition was correlated with better retention than the five visits/week condition . A significant interaction emerged between intake urine and visit frequency ; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition , while exhibiting no reduction in the 2 days/week condition . Patients cocaine positive at intake were better retained with infrequent visits . In study 2 , a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group . These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving . Study 1 also points to setting conditions modulating treatment outcome BACKGROUND In an 18-month exercise intervention in previously sedentary older women ( 40 - 65 years ) , we examined whether an initial 6 months of supervised exercise leads to greater long-term retention and adherence to regular physical activity than an unsupervised home-based program and whether these outcomes are influenced by the exercise intensity . METHODS Women ( N = 126 ) were recruited from the community and r and omly assigned to either center-based or home-based exercise three times/week . The center-based group attended supervised sessions for 6 months , while after 10 initial sessions the home-based group exercised at home . After 6 months both groups were home-based for a further 12 months . Within each arm , subjects were further r and omized to exercise at either moderate or vigorous intensity . RESULTS The center-based group had higher retention than the home-based ( 97 , 94 , 81 versus 87 , 76 , and 61 % ) at 6 , 12 , and 18 months , respectively ( P < 0.05 ) . At 6 months , adherence was higher in the center-based group ( 84 versus 63 % , P < 0.001 ) and energy expenditure was higher at 6 ( P < 0.05 ) and 12 ( P < 0.01 ) months . At 18 months , retention was higher with moderate exercise ( P < 0.05 ) , while adherence was similar with both intensities . CONCLUSION An initial 6 months of center-based exercise enhanced retention in both the short and the long term and promoted short-term adherence and energy expenditure . Long-term , moderate exercise retained more subjects , but had little influence on adherence Objective : To assess whether length of question naire affects response rates . Methods : A quasi-r and omised trial of women aged 70 years and over in a general practice in Engl and . Three question naires of different lengths : a clinical question naire ( four pages ) ; the same question naire plus the EuroQol ( five pages ) ; the same question naire plus the SF-12 ( seven pages ) . The impact of length on the proportion of returned question naires and item completion rates was assessed . Results : In total , 847 question naires were mailed ; response rates were 49 % , 49 % and 40 % to the short , medium and long question naires , respectively . This difference was statistically significant when the short question naire was compared against the longest instrument ( 9 % difference ; 95 % confidence interval ( CI ) of difference=0.3 % to 16.6 % ) . Item completion rates for the clinical question naire did not differ . Respondents did not differ in age or self-reported health status between the three groups . Conclusions : Increasing the length of a question naire from five to seven pages reduces response rates from women aged 70 years and over . However , lengthening a question naire does not seem to affect the quality of responses to questions near the front of the question naire to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy . Design Multicentre individually r and omised controlled trial , nested within the NHS cervical screening programmes . Setting Grampian , Tayside , and Nottingham . Participants 1983 women , aged 20 - 59 , with cytology showing borderline nuclear abnormalities or mild dyskaryosis , October 1999-October 2002 . Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment ( by large loop excision ) if these showed cervical intraepithelial neoplasia grade II or III or worse . Participants were followed for three years , concluding with an exit colposcopy . Main outcome measures Clinical end points : cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years . Clinical ly significant anxiety and depression and self reported after effects assessed six weeks after colposcopy , biopsies , or large loop excision . Results 879 women ( 44 % ) had a normal transformation zone at colposcopy and had no further procedures at that time . Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision ( 603 ( 60 % ) in the biopsy and selective recall group ; 501 ( 51 % ) in the immediate large loop excision group ) . Of women r and omised to biopsy and recall , 157 ( 16 % ) required a second clinic visit for treatment . Specimens from almost 60 % ( n=296 ) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia ( 31 % ; n=156 ) or showed cervical intraepithelial neoplasia grade I ( 28 % ; n=140 ) . The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22 % ( n=216 ) in the biopsy and recall arm and 23 % ( n=228 ) in the immediate large loop excision arm . There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse ( adjusted relative for risk large loop excision v biopsy 1.04 , 95 % confidence interval 0.86 to 1.25 ) or grade III or worse ( 1.03 , 0.79 to 1.34 ) . A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm , but time of detection did not differ significantly between arms . Levels of anxiety and depression and reported pain did not differ between arms . Higher proportions of women r and omised to large loop excision reported moderate or more severe bleeding and discharge . Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy . Immediate large loop excision results in overtreatment and more after effects and should not be recommended . Trial Registration IS RCT N 34841617 Objective To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression . Design Multisite r and omised controlled trial . Setting Seven health regions across Ontario , Canada . Participants 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and r and omised with an internet based r and omisation service . Intervention Proactive individualised telephone based peer ( mother to mother ) support , initiated within 48 - 72 hours of r and omisation , provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session . Main outcome measures Edinburgh postnatal depression scale , structured clinical interview-depression , state-trait anxiety inventory , UCLA loneliness scale , and use of health services . Results After web based screening of 21 470 women , 701 ( 72 % ) eligible mothers were recruited . A blinded research nurse followed up more than 85 % by telephone , including 613 at 12 weeks and 600 at 24 weeks postpartum . At 12 weeks , 14 % ( 40/297 ) of women in the intervention group and 25 % ( 78/315 ) in the control group had an Edinburgh postnatal depression scale score > 12 ( χ2=12.5 , P<0.001 ; number need to treat 8.8 , 95 % confidence interval 5.9 to 19.6 ; relative risk reduction 0.46 , 95 % confidence interval 0.24 to 0.62 ) . There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services . For ethical reasons , participants identified with clinical depression at 12 weeks were referred for treatment , result ing in no differences between groups at 24 weeks . Of the 221 women in the intervention group who received and evaluated their experience of peer support , over 80 % were satisfied and would recommend this support to a friend . Conclusion Telephone based peer support can be effective in preventing postnatal depression among women at high risk . Trial registration IS RCT N 68337727 OBJECTIVES Although cervical cancer is one of the potentially most preventable malignancies , it is still fairly common . In setting s with established screening programs , increased compliance is important for future reduction in cervical cancer incidence , but it is presently unclear how this can be effectively achieved . METHODS We conducted a r and omized controlled trial including all 12,240 women invited to organized screening in Sweden . To increase compliance , three successive interventions were tested : ( a ) modified invitation versus the st and ard invitation letter , ( b ) reminder letter to nonattenders after the first intervention versus no reminder letter , and ( c ) phone reminder to nonattenders after the reminder letter versus no phone reminder . We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities . RESULTS The modified invitation did not increase attendance compared with the st and ard invitation letter [ difference 1.3 % 95 % confidence interval ( CI ) -0.3 to 2.9 ] . In contrast , a reminder letter increased the proportion of women attending with 9.2 % ( 95 % CI 7.9 - 10.5 ) compared with women who did not receive a reminder letter , and a phone reminder increased the proportion of women attending with 31.4 % ( 95 % CI 26.9 - 35.9 ) . Combinations of modified invitation , written reminder , and phone reminder almost doubled attendance within 12 months , and the number of detected cytologic abnormalities was more than tripled . CONCLUSIONS Simple reminders by mail and phone can drastically increase women 's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives Background Recruitment and retention of patients and healthcare providers in r and omised controlled trials ( RCTs ) is important in order to determine the effectiveness of interventions . However , failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear . We sought to describe a strategy used in a multicentre RCT in primary care , to report research ers ' and participants ' experiences of its implementation and to inform future strategies to maximise recruitment and retention . Methods In total 48 general practice s and 903 patients were recruited from three different areas of Irel and to a RCT of an intervention design ed to optimise secondary prevention of coronary heart disease . The recruitment process involved telephoning practice s , posting information , visiting practice s , identifying potential participants , posting invitations and obtaining consent . Retention involved patients attending review s and responding to question naires and practice s facilitating data collection . Results We achieved high retention rates for practice s ( 100 % ) and for patients ( 85 % ) over an 18-month intervention period . Pilot work , knowledge of the setting , awareness of change in staff and organisation amongst participant sites , rapid responses to queries and acknowledgement of practitioners ' contributions were identified as being important . Minor variations in protocol and research support helped to meet varied , complex and changing individual needs of practitioners and patients and encouraged retention in the trial . A collaborative relationship between research er and practice staff which required time to develop was perceived as vital for both recruitment and retention . Conclusion Recruiting and retaining the numbers of practice s and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results . A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances , whilst not compromising trial protocol s , should allow maximal recruitment and retention . Trial registration IS RCT Background In clinical trials , both unequal r and omization design and sequential analyses have ethical and economic advantages . In the single-stage- design ( SSD ) , however , if the sample size is not adjusted based on unequal r and omization , the power of the trial will decrease , whereas with sequential analysis the power will always remain constant . Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio ( R ) was not equal . Methods We evaluated the influence of R , the ratio of the patients in experimental group to the st and ard group , on the statistical properties of two-sided tests , including the two-sided single triangular test ( TT ) , double triangular test ( DTT ) and SSD by multiple simulations . The average sample size numbers ( ASNs ) and power ( 1-β ) were evaluated for all tests . Results Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12 % and the ASN of the TT and DTT by the same proportion . Moreover , when R = 2 , compared to the adjusted SSD , using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1 , compared to SSD . In addition , when R = 2 , compared to SSD , using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1 , but maintains the power of the test to its planned value . Conclusion This study indicates that when the allocation ratio is not equal among the treatment groups , sequential analysis could indeed serve as a compromise between ethicists , economists and statisticians This article describes the recruitment and retention strategies implemented for a prospect i ve , r and omized , clinical trial conducted at a single study facility . The purpose of the study was to examine the effects of a nutritional intervention to reduce the episodes of diarrhea in patients with the human immunodeficiency virus/acquired immune deficiency syndrome . This article review s the challenges faced by the research team during the conduct of the study and discusses the approaches implemented to reduce the barriers to study participation Purpose : The purpose of this study was to enhance retention among African American men enrolled in a cancer screening trial . Design and Methods : A telephonebased , r and omized trial design was used . The intervention group included 352 African American men aged 55 + . Case managers contacted participants at least monthly and provided information and referral services to participants and their relatives . Results : The mean age of participants was 65.7 years . A total of 14,978 calls were made result ing in 780 referrals . The 10 most frequent referrals were for scheduling medical appointments , health information , insurance information , legal aid , transportation , cancer screening information , information technology/computer information , employment , housekeeping/chore services , and food programs . Conclusions : The case managers served as links between participants and community-based re sources . The types of referrals made could be associated with the age-related needs of the participants BACKGROUND Previous studies indicate that yoga may be an effective treatment for chronic or recurrent low back pain . OBJECTIVE To compare the effectiveness of yoga and usual care for chronic or recurrent low back pain . DESIGN Parallel-group , r and omized , controlled trial using computer-generated r and omization conducted from April 2007 to March 2010 . Outcomes were assessed by postal question naire . ( International St and ard R and omised Controlled Trial Number Register : IS RCT N 81079604 ) SETTING 13 non-National Health Service premises in the United Kingdom . PATIENTS 313 adults with chronic or recurrent low back pain . INTERVENTION Yoga ( n = 156 ) or usual care ( n = 157 ) . All participants received a back pain education booklet . The intervention group was offered a 12-class , gradually progressing yoga program delivered by 12 teachers over 3 months . MEASUREMENTS Scores on the Rol and -Morris Disability Question naire ( RMDQ ) at 3 ( primary outcome ) , 6 , and 12 ( secondary outcomes ) months ; pain , pain self-efficacy , and general health measures at 3 , 6 , and 12 months ( secondary outcomes ) . RESULTS 93 ( 60 % ) patients offered yoga attended at least 3 of the first 6 sessions and at least 3 other sessions . The yoga group had better back function at 3 , 6 , and 12 months than the usual care group . The adjusted mean RMDQ score was 2.17 points ( 95 % CI , 1.03 to 3.31 points ) lower in the yoga group at 3 months , 1.48 points ( CI , 0.33 to 2.62 points ) lower at 6 months , and 1.57 points ( CI , 0.42 to 2.71 points ) lower at 12 months . The yoga and usual care groups had similar back pain and general health scores at 3 , 6 , and 12 months , and the yoga group had higher pain self-efficacy scores at 3 and 6 months but not at 12 months . Two of the 157 usual care participants and 12 of the 156 yoga participants reported adverse events , mostly increased pain . LIMITATION There were missing data for the primary outcome ( yoga group , n = 21 ; usual care group , n = 18 ) and differential missing data ( more in the yoga group ) for secondary outcomes . CONCLUSION Offering a 12-week yoga program to adults with chronic or recurrent low back pain led to greater improvements in back function than did usual care . PRIMARY FUNDING SOURCE Arthritis Research UK Background There are many barriers to patient participation in r and omised controlled trials of cancer treatments . To increase participation in trials , strategies need to be identified to overcome these barriers . Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in r and omised controlled trials ( RCTs ) of cancer treatments . Methods A systematic review was conducted . Published and unpublished studies in any language were search ed for in fifteen electronic data bases , including MEDLINE , EMBASE , CINAHL and PsycINFO , from inception to the end of 2004 . Studies of any interventions to improve cancer patient participation in RCTs , which reported the change in recruitment rates , were eligible for inclusion . RCTs and non-r and omised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included . Data were extracted by one review er into structured summary tables and checked for accuracy by a second review er . Each included study was assessed against a checklist for method ological quality by one review er and checked by a second review er . A narrative synthesis was conducted . Results Eight studies were identified that met the inclusion criteria : three RCTs , two non-r and omised controlled trials and three observational studies . Six of the studies had an intervention that had some relevance to the UK . There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs , though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer . Although there was no evidence of an effect in any of the studies , the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work . Conclusion There is not a strong evidence -base for interventions that increase cancer patient participation in r and omised trials . Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials Objective Swimming is often recommended in the prevention and treatment of hypertension . Few studies have investigated the effect of swimming training on blood pressure ( BP ) . Our objective was to evaluate 6 months of supervised moderate swimming or walking on BP in previously sedentary , normotensive , older women . Design Women aged 50–70 years ( n = 116 ) were r and omly assigned to a supervised 6-month swimming or walking programme . They were further r and omized to receive usual care or a behavioural intervention package . Methods Exercise comprised 3 sessions/week with a warm-up , cool down , and 30-min of moderate intensity walking or swimming . BP was recorded for 20 min supine , and 5 min st and ing . Assessment s were made at 0 and 6 months . Results At baseline , mean supine BP ( ± SD ) was 115.7 ± 1.3/66.8 ± 0.7 mmHg . Swimming improved swim distance by 78.1 m ( 29.3 % ) [ 95 % confidence interval ( CI ) ; 66.7 , 89.4 ] and walk time by 0.58 min ( 3.8 % ) ( 0.41 , 0.74 ) . Walking decreased walk time by 1.0 min ( 6.5 % ) ( 0.81 , 1.19 ) . After adjustment for initial BP , age , hypertension treatment status and change in weight , swimming increased supine and st and ing systolic BP relative to walking by 4.4 mmHg ( 1.2 , 7.5 ) ( P = 0.008 ) and 6.0 mmHg ( 2.6 , 9.5 ) ( P = 0.001 ) , respectively . Supine and st and ing diastolic BP increased by 1.4 mmHg ( −0.14 , 3.0 ) ( P = 0.07 ) and 1.8 mmHg ( −0.02 , 3.5 ) ( P = 0.05 ) , respectively . Conclusion Relative to moderately paced walking , regular swimming significantly elevates BP in previously sedentary , normotensive , older women . This finding may have important implication s for exercise prescription in older subjects Summary Background Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term . We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence , which was biochemically verified at 6 months . Methods In this single-blind , r and omised trial , undertaken in the UK , smokers willing to make a quit attempt were r and omly allocated , using an independent telephone r and omisation system , to a mobile phone text messaging smoking cessation programme ( txt2stop ) , comprising motivational messages and behavioural-change support , or to a control group that received text messages unrelated to quitting . The system automatically generated intervention or control group texts according to the allocation . Outcome assessors were masked to treatment allocation . The primary outcome was self-reported continuous smoking abstinence , biochemically verified at 6 months . All analyses were by intention to treat . This study is registered , number IS RCT N 80978588 . Findings We assessed 11 914 participants for eligibility . 5800 participants were r and omised , of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group ; eight were excluded because they were r and omised more than once . Primary outcome data were available for 5524 ( 95 % ) participants . Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group ( 10·7 % txt2stop vs 4·9 % control , relative risk [ RR ] 2·20 , 95 % CI 1·80–2·68 ; p<0·0001 ) . Similar results were obtained when participants that were lost to follow-up were treated as smokers ( 268 [ 9 % ] of 2911 txt2stop vs 124 [ 4 % ] of 2881 control [ RR 2·14 , 95 % CI 1·74–2·63 ; p<0·0001 ] ) , and when they were excluded ( 268 [ 10 % ] of 2735 txt2stop vs 124 [ 4 % ] of 2789 control [ 2·20 , 1·79–2·71 ; p<0·0001 ] ) . No significant heterogeneity was shown in any of the prespecified subgroups . Interpretation The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services . Funding UK Medical Research Council , Primary Care Research Networks Participant attrition and attendance at follow-up were examined in a multicenter , r and omized , clinical trial . The Lung Health Study ( LHS ) enrolled a total of 5887 adults to examine the impact of smoking cessation coupled with the use of an inhaled bronchodilator on chronic obstructive pulmonary disease ( COPD ) . Of the initial LHS 1 volunteers still living at the time of enrolment in LHS 3 ( 5332 ) , 4457 ( 84 % ) attended the LHS 3 clinic visit , a follow-up session to determine current smoking status and lung function . The average period between the beginning of LHS 1 and baseline interview for LHS 3 was 11 years . In univariate analyses , attenders were older , more likely female , more likely to be married , smoked fewer cigarettes per day , and were more likely to have children who smoked at the start of LHS 1 than non-attenders . Attenders were also less likely to experience respiratory symptoms , such as cough , but had decreased baseline lung function compared with non-attenders . Volunteers recruited via mass mailing were more likely to attend the long-term follow-up visit . Those recruited by public site , worksite , or referral methods were less likely to attend . In multivariate models , age , gender , cigarettes smoked per day , married status , and whether participants ' children smoked were identified as significant predictors of attendance versus non-attendance at LHS 3 using stepwise logistic regression . Treatment condition ( smoking intervention or usual care ) was not a significant predictor of attendance at LHS 3 . Older females who smoked less heavily were most likely to participate . These findings may be applied to improve participant recruitment and retention in future clinical trials Behavioral research has an important role in increasing and maintaining participation in disease prevention trials , both in interventions and in follow-up visits . We conducted a r and omized experiment among participants in the lung cancer chemoprevention trial , CARET ( Carotene and Retinol Efficacy Trial ) to test the effects of providing two incentives on retention . The items used for this study were a Certificate of Appreciation and one of two lapel pins , provided in a 2 2 design . Providing incentives , whether alone or in combination , had no statistically significant effect on retention by the two-year follow-up point . The successful implementation of this r and omized incentive study has two implication s for future research : ( 1 ) study of behavioral interventions and issues is feasible in the context of large controlled trials of disease end-points ; and ( 2 ) such study is necessary to determine whether selected incentives can increase retention The feasibility of collecting DNA through the mail from a cohort of current and former smokers was assessed . Also examined was whether monetary incentives would increase response rates . A r and om sample of 300 subjects , stratified by 20 U.S. communities , was selected to participate . The sampling frame included the 6,726 people who were in both the Community Intervention Trial for Smoking Cessation ( COMMIT ) between 1988 and 1993 and the follow-up study in 2001 , and who consented to being contacted again . Subjects were further r and omized within communities to incentive arms of 10 US dollars , 2 US dollars , or 0 US dollars . A total of 110 usable sample s were returned ( 37 % ) , and the 10 US dollars incentive arm had the highest response ( 43 % ) . Logistic regression revealed no significant predictors of sending a DNA sample , although in a larger study , similar-sized odds ratios would be statistically significant for subjects who received the 10 US dollars incentive and for those who were White , female , or college graduates or whose household incomes were more than 60,000 US dollars per year . The spectrophotometer-determined median DNA yield was 44.93 microg ( range=4.00 - 425.86 microg ) . Assuming that 50 ng of DNA would be needed for polymerase chain reaction amplification to determine any given genotype , 80 - 8,517 runs would be attainable . Qualitative findings suggest several method ological improvements to boost response rates . Institutional review board requirements , which are st and ardized on the inpatient , clinical protocol model , stipulated that noninstitutionally based subjects needed a witness to initial and date every page as well as sign the consent form . This pilot study showed that this requirement could pose some challenges in population -based research The report aims to review the literature and describe the methods used for retention of patients in a clinical study . The Enhanced Recovery in Coronary Heart Disease ( ENRICHD ) trial was a multicenter , r and omized clinical trial design ed to evaluate the effects of a psychosocial intervention on cardiovascular morbidity and mortality . A total of 2481 patients met the criteria for depression , low social support , or both after a myocardial infa rct ion and needed to be followed . Follow-up evaluation consisted of telephone interviews 3 , 9 , 12 , 24 , 36 , and 48 months after enrollment and clinic visits scheduled at 6 , 18 , 30 , 42 , and 54 months . Creative strategies used to achieve optimum retention of this complex patient population over a long follow-up period are presented . Strategies to enhance adherence throughout the course of the trial required adequate tracking of patients to ensure minimum dropout , follow-up evaluation optimized through multiple methods of contact to guarantee completeness of data collection ; and development of procedures to address the needs of patients at risk for dropout . Patients in the group that completed the study participated for a mean of 28.3 months , and those lost to follow-up evaluation participated for a mean of 19 months . Retention was not substantially different by gender or minority status . The results of this project can assist investigators in planning studies that require patient follow-up evaluation , and can provide clinicians with specific strategies for maximizing retention-to-treatment recommendations . As a result of the retention strategies described in this report , 93.02 % of the patients completed their study participation or died . This is a very high retention rate given the complexity of the study sample , protocol , and required duration of follow-up evaluation 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 Postal question naires are widely used to collect outcome data on participants . However , a poor response to question naires will reduce the statistical power of the study and may introduce bias . A meta analysis of ten trials offering study results , largely in the fields of education and marketing , was shown to be ineffective , with the odds ratio for response with offering research findings is 0.92 ( 95 % CI 0.75 to 1.11 ) . However uncertainty still exists as it is uncertain whether results from such trials can be extrapolated to that of a health care setting . The aim of this study was to assess whether offering participants study results increases the response rates to postal question naires . Methods 1038 women aged over 70 years were remotely r and omised by computer in a 3:1 ratio . 250 participants did not receive the offer of knowing the results of the trial and 788 participants were offered the results of the trial in a postal question naire . The main outcome measure was response rate . Chi square test was used to evaluate the overall differences in response rate between the two groups . An adjusted analysis , adjusting for whether the participant was taking calcium and age was also undertaken . Results The response rates were not significantly different Odds Ratio 0.88 ( 95 % confidence intervals 0.48 to 1.63 ) p = 0.69 . Conclusion Offering study results to women living in the community aged over 70 does not increase response rates to postal question naires . Although research ers have an ethical obligation to offer participants study results , since 10 % of women did not wish to receive the results , investigators should give participants the option to opt out of receiving the study 's results Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( < 58 kg ) , smoker , family history of hip fracture , or fair or poor self reported health . Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry Objectives To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests . Design Multicentre individually r and omised controlled trial . Setting NHS cervical screening programmes in Grampian , Tayside , and Nottingham . Participants 4439 women , aged 20 - 59 , with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis , October 1999-October 2002 . Interventions Cytological screening every six months in primary care ( n=2223 ) or referral for colposcopy and related interventions ( n=2216 ) . All women were followed for three years , concluding with an exit appointment at which colposcopic examination was undertaken . Colposcopists assessing outcome at this appointment were blinded to r and omisation . Main outcome measures Primary end point : cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease . Other end points : cervical intraepithelial neoplasia grade III or worse , clinical ly significant anxiety and depression , other self reported after effects , and rates of non-attendance . Analysis was by intention to treat ; all those r and omised were included . Results The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm ( relative risk 1.37 , 95 % confidence interval 1.19 to 1.57 ) . This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease , but the incidence was still higher in the colposcopy arm ( relative risk 1.26 , 1.04 to 1.53 ) . Among women r and omised to immediate colposcopy , 79 % ( 74.9 % to 82.5 % ) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy , while among women r and omised to cytological surveillance , 77 % ( 72.1 % to 81.2 % ) of cases were detected by surveillance cytology and related interventions . Similar proportions of women were anxious or depressed in the two arms . A higher proportion of women in the colposcopy arm reported after effects , and these were of longer duration and more severe . Non-attendance was low in both arms . Conclusion The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia . Compared with cytological surveillance , a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse , and some more grade III or worse , but might lead to overtreatment . Such a policy is associated with a higher rate of reported after effects , which are more severe and of longer duration than those associated with cytological surveillance . Trial registration IS RCT N 34841617 M and ates to include women and minority population s in research have heightened the need to identify successful recruitment strategies . This paper describes the recruitment and retention strategies used as part of a r and omized controlled trial ( RCT ) of a physical activity and dietary intervention targeting low-income , predominantly Latino patients in a primary health care clinic . Data on the recruitment and retention rates and the representativeness of participants are presented . Strategies included hiring bilingual staff , translating and culturally adapting intervention material s and soliciting ongoing consultation from patients , clinicians and organizations providing services to the Latino community . The primary recruitment procedure involved letters from physicians followed by phone calls from project staff to patients identified from electronic medical records . Two hundred patients were recruited into the RCT ( 78 % of those reached and eligible ) , with 69 and 81 % reached for the 6-week and 6-month follow-ups , respectively . Women were more likely to both participate and remain in the trial , and there was a trend toward greater recruitment and retention of Spanish speakers . By engaging the community , clinicians and patients , this study was able to successfully recruit and retain a large proportion of this often difficult to reach Latino sub- population of patients with multiple chronic conditions Mail surveys have been used to follow-up early participants in a Canadian breast cancer prevention trial . To minimize non-response bias , we undertook a r and omized study of two postal strategies , of which one was our usual procedure and the other was a systematic application , known as the total design method ( TDM ) and described by Dillman . The response rates to the two methods were 62 and 88 % respectively . The TDM is a practical , cost-efficient approach to reducing non-response bias in postal surveys and as such has an important role in epidemiological research which involves healthy participants CONTEXT No effective pharmacotherapies exist for cocaine dependence , although contingency management ( CM ) has demonstrated efficacy . OBJECTIVE To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals . DESIGN This 25-week , placebo-controlled , double-blind trial r and omly assigned participants to 1 of 4 treatment conditions : CM and placebo ( CMP ) , CM and 300 mg/d of bupropion hydrochloride ( CMB ) , voucher control and placebo ( VCP ) , or voucher control and bupropion ( VCB ) . SETTING Outpatient clinic at the Veterans Affairs Connecticut Healthcare System . PARTICIPANTS A total of 106 opiate-dependent , cocaine-abusing individuals . INTERVENTIONS All study participants received methadone hydrochloride ( range , 60 - 120 mg ) . Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3 . In the CM conditions , each urine sample negative for both opioids and cocaine result ed in a monetary-based voucher that increased for consecutively drug-free urine sample s during weeks 1 to 13 . Completion of abstinence-related activities also result ed in a voucher . During weeks 14 to 25 , only completion of activities was reinforced in the CM group , regardless of sample results . The voucher control groups received vouchers for su bmi tting urine sample s , regardless of results , throughout the study . MAIN OUTCOME MEASURE Thrice-weekly urine toxicologic test results for cocaine and heroin . RESULTS Groups did not differ in baseline characteristics or retention rates . Opiate use decreased significantly , with all treatment groups attaining equivalent amounts of opiate use at the end of the study . In the CMB group , the proportion of cocaine-positive sample s significantly decreased during weeks 3 to 13 ( P<.001 ) relative to week 3 and remained low during weeks 14 to 25 . In the CMP group , cocaine use significantly increased during weeks 3 to 13 ( P<.001 ) relative to week 3 , but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 ( P<.001 ) . In contrast , by treatment end , the VCB and VCP groups showed no significant improvement in cocaine use . CONCLUSION These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone BACKGROUND Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy . Yet little is known about factors associated with premature treatment termination among depressed patients . METHODS This study examines predictors of , time to , and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult out patients , age 18 - 75 , with chronic major depression who were r and omly assigned to nefazadone alone ( MED ) , cognitive behavioral analysis system of psychotherapy alone ( CBASP ) or both treatments ( COMB ) . RESULTS Of 681 r and omized study participants , 156 were defined as dropouts . Dropout rates were equivalent across the three treatments . Among dropouts , those in COMB remained in treatment ( Mean=40 days ) significantly longer than those in either MED ( Mean=27 days ) or CBASP ( Mean=28 days ) . Dropouts attributed to medication side-effects were significantly lower in COMB than in MED , suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications . Ethnic or racial minority status , younger age , lower income , and co-morbid anxiety disorders significantly predicted dropout in the full sample . Within treatments , differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED . Among those receiving CBASP , dropouts had significantly lower therapeutic alliance scores than completers . LIMITATIONS The sample included only individuals with chronic depression . CONCLUSIONS Predictors of dropout included baseline patient characteristics , but not early response to treatment . Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination , particularly in pharmacotherapy , and may require modified treatment strategies Women with inadequate prenatal care were recruited to a multi-component parenting intervention study . Because it was anticipated that this high-risk population might present challenges to retention , a variety of strategies were employed to maintain their participation in the study . This report review s the results of these retention efforts and compares the population that completed the study versus those that terminated prior to study completion . Two hundred and eighty-six women were r and omized to an intervention or control group . Careful tracking of the mothers , offering incentives for completing various study activities and providing a culturally competent staff were among the strategies employed to maintain participation . Comparison was made of those mothers terminating before study completion versus those retained , and of those terminating early in the study period versus later . Despite retention efforts , attrition at a level of 41 % occurred . A few characteristics of mothers terminating early from the study were significant including older maternal age , a larger number of children , and incidence of no prenatal care . Despite comprehensive tracking procedures , some mothers were lost to follow up after change of residence . Other reasons for attrition included child outplacement and refusal of services or data collection procedures Objectives : This study was design ed to detect any effect of order when modules on disease-specific and overall health status are combined in an outcomes research question naire . Methods : Men with symptomatic benign prostatic hyperplasia ( BPH ) were prospect ively enrolled in a clinical trial of an educational intervention in Group Health Cooperative of Puget Sound , a prepaid group practice . Within the trial , 392 consecutive men were r and omized to one of two versions of a baseline question naire . One had a 38-item module on BPH-specific health status first , followed by a 30-item module on overall health status ; the other had the modules in reverse order . Scores were compared for three BPH-specific scales and eight scales measuring overall health . Data were collected in the form of self-administered question naires . Results : Comparing the groups assigned the two versions of the question naire , no significant differences in scores on any of the health status scales were found . Conclusions : In this data set , we could find no evidence of an order effect when modules on BPH-specific and overall health status were combined in different sequences BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias . They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs , but the relative efficacy of these two treatment strategies is unknown . METHODS To address this issue , we conducted a r and omized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia . Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms , along with a left ventricular ejection fraction of 0.40 or less . One group of patients was treated with implantation of a cardioverter-defibrillator ; the other received class III antiarrhythmic drugs , primarily amiodarone at empirically determined doses . Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years . Of 1016 patients ( 45 percent of whom had ventricular fibrillation , and 55 percent ventricular tachycardia ) , 507 were r and omly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy . The primary end point was overall mortality . RESULTS Follow-up was complete for 1013 patients ( 99.7 percent ) . Overall survival was greater with the implantable defibrillator , with unadjusted estimates of 89.3 percent , as compared with 82.3 percent in the antiarrhythmic-drug group at one year , 81.6 percent versus 74.7 percent at two years , and 75.4 percent versus 64.1 percent at three years ( P<0.02 ) . The corresponding reductions in mortality ( with 95 percent confidence limits ) with the implantable defibrillator were 39+/-20 percent , 27+/-21 percent , and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms , the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival Objectives —To determine the effect of different methods of administering a diary to collect information from parents on near miss and minor injuries on responses , completeness and accuracy , the number of incidents reported , the effect of a financial incentive on response , and the cost of administering each method . Setting —The study was set within the context of a cluster r and omised controlled trial of injury prevention in 36 practice s in Nottingham . Methods —The study population comprised the 1594 parents who responded to the baseline question naire . Parents were allocated systematic ally to one of four groups : postal administration , with and without financial incentive , telephone administration , with and without financial incentive ( 102 in each group ) . A clinic visit method with and without financial incentive ( 50 in each group ) was also used . Results —A significant trend was found , with decreasing response rates with increasing degree of contact with the parent , such that administering the diary in the clinic had the lowest response ( χ2 for trend = 5.54 , 1 df , p = 0.02 ) . Offering a financial incentive increased responses from 47 % to 59 % ( χ2=5.78 , 1 df , p = 0.016 ) . The most complete recording was found in the diaries h and ed out at clinic visits . Importantly , parents were accurate in their recording of near miss and minor injuries , suggesting they understood the differences between the two types of incident . Postal methods were the least expensive method of administering the diary in terms of average cost per returned diary . Using a financial incentive result ed in a lower cost per returned diary for telephone and clinic visit methods . Conclusions —Parents can accurately and reliably complete diaries recording near miss and minor injuries occurring to their preschool children . More work is needed to investigate methods of increasing response . Postal diaries achieve the highest response but have the least complete recording of data . Diaries administered through child health clinics were most complete but achieved the lowest response . The administration method chosen in future work should be influenced both by the response and completeness of recording that is required by the research BACKGROUND AND OBJECTIVES It is important to maximize response rates to postal question naires . We compared the impact of three low-cost interventions on response rates . METHODS A 2 x 2 x 2 factorial trial was conducted , nested within TOMBOLA ( Trial Of Management of Borderline and Other Low- grade Abnormal smears ) . Three interventions were evaluated : ( 1 ) enclosing a TOMBOLA-br and ed pen with the question naire ( as opposed to no pen ) ; ( 2 ) sending the question naires by first class post ( as opposed to second class ) ; and ( 3 ) enclosing a preaddressed return envelope on which there was a second class postage stamp ( rather than a freepost business-reply envelope ) . Nine hundred thirty women , aged 20 - 59 years , due to receive a TOMBOLA psychosocial question naire by post during June-August 2003 were r and omized . RESULTS Enclosing a pen result ed in a statistically significant 7.0 % increase in the cumulative proportion of question naires returned ( from 61.5 to 68.5 % ; P = .002 ) . The adjusted odds of response was significantly raised ( odds ratio [ OR ] = 1.38 , 95 % confidence interval [ CI ] 1.04 - 1.82 ) . Neither first class post nor providing a stamped envelope had a significant impact on response . There were no interactions between the interventions . CONCLUSIONS Enclosing a pen with a question naire can significantly increase response . This low-cost strategy was effective against a background of " good practice " with regard to the administration of postal question naires OBJECTIVE This study was conducted to determine whether early initiation of combined hormonal contraception under direct clinical observation following successful medical abortion increases continuation rates with the method compared to traditional " Sunday start . " STUDY DESIGN Women enrolled in a multicenter medical abortion trial with mifepristone and misoprostol who requested combined hormonal contraception ( pill , ring or patch ) following medical abortion were recruited . Women were r and omized to initiate the method under supervision either at the 1-week medical abortion follow-up visit ( " observed start " ) or at the first Sunday following this visit ( " Sunday start " ) . Primary outcome was continuation of the chosen method at 6 weeks . RESULTS Of the 1128 women in the primary trial , 261 subjects enrolled in this sub study and 36/261 ( 13.8 % ) were lost to follow-up . There was no significant difference in method continuation at 6 weeks [ observed start 108/114 ( 94.7 % ) , Sunday start 101/111 ( 91.0 % , p=.27 ] . CONCLUSION Short-term continuation rates among those choosing hormonal contraception following medical abortion are high and are not significantly improved by initiating the method at the time of the first follow-up visit OBJECTIVE The purpose of this study was to determine the effectiveness of interventions design ed to improve follow-up after an abnormal Pap smear . METHODS We performed a qualitative meta- analysis of interventions design ed to improve follow-up after an abnormal Pap smear and included studies that met the following criteria : r and omized or concurrently controlled study design , defined outcomes , and data available for abstract ion . Interventions were classified as behavioral , cognitive , sociologic , or combined strategies ( e.g. , behavioral and cognitive ) . Abnormal Pap smears were defined as any test result requiring additional follow-up . Effectiveness was measured by the rate of compliance with recommended follow-up . RESULTS Twenty-two interventions in 10 studies met the inclusion criteria . Cognitive interventions utilizing interactive telephone counseling were the most effective , improving compliance by 24 to 31 % . Behavioral interventions , such as patient reminders , were also effective , increasing follow-up by up to 18 % . Not all of these results achieved statistical significance . The single sociologic intervention we identified used video-taped peer discussion s to provide a message about abnormal Pap smears and appropriate follow-up . This intervention was not associated with increased follow-up after an abnormal test . The effectiveness of interventions using multiple types of strategies to improve follow-up was inconsistent . CONCLUSIONS Cognitive strategies led to the greatest improvement in compliance with follow-up of abnormal Pap smear screening tests . Extension of similar interventions to follow-up of abnormal breast and colon cancer screening , development of physician- and system-targeted interventions , and evaluation of the cost-effectiveness of these strategies are important priorities for future research OBJECTIVE To examine in previously sedentary older women the effects of exercise mode and a behavioural intervention on short and long-term retention and adherence . METHODS Healthy , sedentary women aged 50 - 70 years ( N=116 ) were r and omly assigned to a supervised 6-month swimming or walking program 3 sessions a week . They were further r and omised to usual care or a behavioural intervention . The same program was further continued unsupervised for 6 months . We assessed retention , adherence , stage of exercise behaviour and changes in fitness . RESULTS One hundred women ( 86 % ) completed 6 months and 86 ( 74 % ) continued for 12 months . Retention rates were similar for both exercise modes at 6 and 12 months . Adherence to swimming or walking was similar after 6 months ( 76.3 ( 95 % CI : 69.5 , 83.1)% vs. 74.3 ( 67.7 , 80.9)% ) and 12 months ( 65.8 ( 57.9 , 73.8)% vs. 62.2 ( 54.6 , 70.0)% ) . The behavioural intervention did not enhance retention or adherence . Fitness improved for both exercise modes after 6 months and was maintained at 12 months . CONCLUSIONS Either swimming or walking programs initiated with careful supervision over 6 months result ed in similar high retention and adherence rates by highly motivated older women over 12 months . Behavioural intervention in this setting did not improve these rates further OBJECTIVE We aim to evaluate the effectiveness of electronic reminders ( ERs ) to improve the response rates and time to response of postal question naires in a health research setting . STUDY DESIGN AND SETTING This pragmatic r and omized controlled trial ( RCT ) was nested within a multicenter RCT of yoga for lower back pain . Participants who provided an electronic mail address and /or mobile phone number were r and omized to receive an ER or no reminder ( controls ) on the day they were due to receive a follow-up question naire . RESULTS One hundred twenty-five participants ( 32 males and 93 females ) mean age 46 ( st and ard deviation : 11 , range : 20 - 65 ) were r and omized to ER ( n=62 ) or controls ( n=63 ) . Overall 85.6 % of participants returned postal question naires ( 87.1 % ER group and 84.1 % from controls ) . No significant differences were found between the two groups for response rate ( difference between groups=3.0 % , 95 % confidence interval [CI]=-10 , 16 ; P=0.64 ) or time to response after adjusting for age , gender , and treatment allocation ( χ(2 ) ([3df])=7.10 ; P=0.07 ) . CONCLUSION In the present RCT , we found little evidence for the effectiveness of ERs to increase response rates or time to respond for the return of question naires in this study population group This article describes the results of an eight-month follow-up investigation from a r and omized controlled trial of day hospital psychotherapy ( DHP ) compared with outpatient individual psychotherapy ( OIP ) for patients with personality disorders ( N=114 ) . The patients were r and omly assigned to either 18 weeks of day hospital treatment followed by long-term conjoint group and individual therapy ( DHP ) , or outpatient individual psychotherapy ( OIP ) . The main outcome measures were attrition rate , suicide attempts , suicidal thoughts , self-injury , psychosocial functioning , symptom distress , and interpersonal and personality problems . The study showed a low dropout rate and a moderate improvement on a broad range of clinical measures for both treatments . However , there was no indication of the superiority of one treatment over the other . Neither was there any indication that day hospital treatment was better for the most poorly functioning patients . Further studies will follow this group of patients for the next few years , the results of which may have implication s for re source allocation and the organization of mental health services for patients with personality disorders Background Attrition from follow-up is a major method ological challenge in r and omized trials . Incentives are known to improve response rates in cross-sectional postal and online surveys , yet few studies have investigated whether they can reduce attrition from follow-up in online trials , which are particularly vulnerable to low follow-up rates . Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial . Methods Two r and omized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption ( the Down Your Drink r and omized controlled trial , DYD- RCT ) . Participants were those in the DYD pilot trial eligible for 3-month follow-up ( study 1 ) and those eligible for 12-month follow-up in the DYD main trial ( study 2 ) . Participants in both studies were r and omly allocated to receive an offer of an incentive or to receive no offer of an incentive . In study 1 , participants in the incentive arm were r and omly offered a £ 5 Amazon.co.uk gift voucher , a £ 5 charity donation to Cancer Research UK , or entry in a prize draw for £ 250 . In study 2 , participants in the incentive arm were offered a £ 10 Amazon.co.uk gift voucher . The primary outcome was the proportion of participants who completed follow-up question naires in the incentive arm(s ) compared with the no incentive arm . Results In study 1 ( n = 1226 ) , there was no significant difference in response rates between those participants offered an incentive ( 175/615 , 29 % ) and those with no offer ( 162/611 , 27 % ) ( difference = 2 % , 95 % confidence interval [ CI ] –3 % to 7 % ) . There was no significant difference in response rates among the three different incentives offered . In study 2 ( n = 2591 ) , response rates were 9 % higher in the group offered an incentive ( 476/1296 , 37 % ) than in the group not offered an incentive ( 364/1295 , 28 % ) ( difference = 9 % , 95 % CI 5 % to 12 % , P < .001 ) . The incremental cost per extra successful follow-up in the incentive arm was £ 110 in study 1 and £ 52 in study 2 . Conclusion Whereas an offer of a £ 10 Amazon.co.uk gift voucher can increase follow-up rates in online trials , an offer of a lower incentive may not . The marginal costs involved require careful consideration . Trial registration IS RCT N31070347 ; http://www.controlled-trials.com/IS RCT N31070347 ( Archived by WebCite at http://www.webcitation.org/5wgr5pl3s Research ers agree that high recruitment and retention rates are essential for longitudinal studies and can be a daunting task . This paper examines retention rates for longitudinal studies of abused women and presents strategies to maximize recruitment and retention . The techniques presented result ed in subject retention rates of 89 % to 100 % in longitudinal prevalence , quasi-experimental , and r and omized clinical trials that followed participants for up to 24 months . The findings point to the importance of establishing and sustaining collaborative partnerships with agencies , multiple contacts sources with study participants , incremental monetary incentives , and a detailed field tracking protocol that includes safety practice Brief measures of health-related quality of life are being used with increased frequency in AIDS clinical trials . Self-administration of question naires can reduce costs in this setting because they require little time . However , the equivalence between self- and interview-administered responses in clinical trials is not known . We evaluated patient and proxy responses to the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) and the EuroQol . We r and omized 68 patients with advanced HIV disease on ( 1 ) mode of administration ( self vs. interview ) ; ( 2 ) type of interview ( face-to-face vs. telephone ) ; ( 3 ) question naire order ( MOS-first vs. EuroQol-first ) ; and ( 4 ) 2- vs. 3-item response categories for physical limitations . There were few differences in scores between self and interview administration and type of interview . Proxy respondents viewed patients as more impaired than did patients themselves on subjective aspects of health including mental health ( 63.8 vs. 75.7 , p < 0.001 ) , health distress ( 67.3 vs. 77.1 , p=0.007 ) , pain ( 64.4 vs. 70.0 , p=0.04 ) , and vitality ( 48.4 vs. 55.5 , p=0.04 ) . Results concerning question naire order and number of response categories were not conclusive . Our results suggest that for patients with advanced HIV disease , data from the MOS-HIV and the EuroQol collected using different modes may be pooled , but that proxy responses should be calibrated OBJECTIVE To assess the efficacy of a Web-based tailored behavioral weight management program compared with Web-based information-only weight management material s. RESEARCH METHODS AND PROCEDURES Participants , 2862 eligible overweight and obese ( BMI = 27 to 40 kg/m2 ) members from four regions of Kaiser Permanente 's integrated health care delivery system , were r and omized to receive either a tailored expert system or information-only Web-based weight management material s. Weight change and program satisfaction were assessed by self-report through an Internet-based survey at 3- and 6-month follow-up periods . RESULTS Significantly greater weight loss at follow-up was found among participants assigned to the tailored expert system than among those assigned to the information-only condition . Subjects in the tailored expert system lost a mean of 3 + /- 0.3 % of their baseline weight , whereas subjects in the information-only condition lost a mean of 1.2 + /- 0.4 % ( p < 0.0004 ) . Participants were also more likely to report that the tailored expert system was personally relevant , helpful , and easy to underst and . Notably , 36 % of enrollees were African-American , with enrollment rates higher than the general proportion of African Americans in any of the study regions . DISCUSSION The results of this large , r and omized control trial show the potential benefit of the Web-based tailored expert system for weight management compared with a Web-based information-only weight management program This study compared the efficacy of disulfiram ( DSF ) and topiramate ( TPM ) for preventing alcoholic relapse in an open study of routine clinical practice in India . One hundred alcohol-dependent men with family members who agreed to encourage medical compliance and to accompany them for follow-up were r and omly allocated to 9 months of treatment with DSF or TPM . Weekly psychotherapy was also provided . There was no blinding of conditions for the psychiatrist , patient , or family members . Supervision and support of the family member were used in the maintenance of compliance among the patients . Alcohol consumption , craving , and adverse events were recorded weekly for 3 months and then biweekly . Serum gamma glutamyl transferase was measured at the start and at the end of the study . At the end of the trial , 92 patients were still in contact . Relapse occurred at a mean of 133 days for DSF as compared with 79 days for TPM . At 9 months , 90 % of DSF patients , as compared with 56 % of TPM patients , remained abstinent . TPM-treated patients did show less craving than DSF patients did . Further comparisons between these drugs in different treatment setting s and patient population s are warranted We conducted a pilot r and omised trial of computerised templates for the management of asthma and diabetes in general practice in six general practice s in North London . Uptake of the guidelines by general practitioners and practice nurses was assessed using qualitative ( semi-structured interviews design ed to assess the users ' views ) and quantitative ( change in use of the template during the study period ) outcome measures . The practice nurses used the templates frequently but general practitioners rarely used them . Several reasons were offered for non-use of the templates , such as the length of the template and non-involvement in the care of asthma or diabetes . Despite this , however , health professionals were favourably disposed to the use of templates for general clinical care . Pilot investigations of computerised templates are best achieved by observational or quasi-experimental methods rather than a r and omised controlled trial . The use of both qualitative and quantitative methods in this study allowed exploration of the barriers to use of computers BACKGROUND Perceptions of personal efficacy have been consistently identified as being determinants of exercise adherence in asymptomatic , rehabilitative , younger , and older population s. The present study incorporated a r and omized control design in an effort to examine the effects of an efficacy-based intervention in enhancing exercise adherence in a large sample ( N = 114 ) of formerly sedentary middle-aged males and females . METHODS Subjects r and omly assigned to an exercise plus intervention group or an exercise plus attentional control group participated in a 5-month long walking program led by trained personnel . Exercise behavior ( frequency , miles walked , duration ) were assessed on a continuous basis and self-efficacy was measured at 1 , 2 , and 4 months . RESULTS Repeated measures multivariate analyses revealed a significant treatment effect with subjects in the intervention group exercising more frequently , for longer duration , and walking greater distances over the course of the program . Path analysis indicated that the effect of the treatment on adherence was direct rather than through self-efficacy as hypothesized . Self-efficacy was , however , a significant predictor of exercise behavior in the early and middle stages of the exercise program but not during the last month . CONCLUSIONS An intervention program design ed to maximize information pertaining to participants ' capabilities appears to have had a reasonable effect on reducing attrition in middle-aged males and females and self-efficacy was a significant predictor of exercise frequency over time . Further research efforts are required to tease out those cognitive factors that might underlie any effects of interventions in exercise adherence OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States . It has been proposed that carotenoids and retinoids are agents that may prevent these disorders . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers , former smokers , and workers exposed to asbestos . The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol ( vitamin A ) in the form of retinyl palmitate per day on the primary end point , the incidence of lung cancer , were compared with those of placebo . RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up ( mean length of follow-up , 4.0 years ) . The active-treatment group had a relative risk of lung cancer of 1.28 ( 95 percent confidence interval , 1.04 to 1.57 ; P=0.02 ) , as compared with the placebo group . There were no statistically significant differences in the risks of other types of cancer . In the active-treatment group , the relative risk of death from any cause was 1.17 ( 95 percent confidence interval , 1.03 to 1.33 ) ; of death from lung cancer , 1.46 ( 95 percent confidence interval , 1.07 to 2.00 ) ; and of death from cardiovascular disease , 1.26 ( 95 percent confidence interval , 0.99 to 1.61 ) . On the basis of these findings , the r and omized trial was stopped 21 months earlier than planned ; follow-up will continue for another 5 years . CONCLUSIONS After an average of four years of supplementation , the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer , cardiovascular disease , and any cause in smokers and workers exposed to asbestos PURPOSE The purpose of this study was to enhance adherence among older ( aged 55 years and older ) African American men enrolled in a cancer screening trial for prostate , lung , and colorectal cancer . For this study , we defined adherence as completing the trial screenings . DESIGN AND METHODS We used a r and omized trial design . Case managers contacted intervention group participants ( n=352 ) at least monthly by telephone and provided information and referral services . The control group included 351 participants . RESULTS Among participants with low income , those in the intervention group had higher screening adherence rates than did participants in the control group for ( a ) prostate-specific antigen test for prostate cancer ( 74.3 % vs 53.0 % , p=.001 ) , ( b ) digital rectal exam for prostate cancer ( 66.2 % vs 46.1 % , p=.011 ) , and ( c ) chest x-ray for lung cancer ( 70.9 % vs 51.3 % , p=.012 ) . We found no statistically significant differences in adherence rates for flexible sigmoidoscopy screening for colorectal cancer . In contrast , among participants with moderate-to-high income , we found no statistically significant differences in adherence rates between intervention and control group participants for any of the screening tests . IMPLICATION S The case management intervention was effective in enhancing adherence among participants with the lowest income , who in many studies are the most difficult to retain BACKGROUND Corticosteroids have been used to treat head injuries for more than 30 years . In 1997 , findings of a systematic review suggested that these drugs reduce risk of death by 1 - 2 % . The CRASH trial -- a multicentre international collaboration-- aim ed to confirm or refute such an effect by recruiting 20000 patients . In May , 2004 , the data monitoring committee disclosed the unmasked results to the steering committee , which stopped recruitment . METHODS 10008 adults with head injury and a Glasgow coma score ( GCS ) of 14 or less within 8 h of injury were r and omly allocated 48 h infusion of corticosteroids ( methylprednisolone ) or placebo . Primary outcomes were death within 2 weeks of injury and death or disability at 6 months . Prespecified subgroup analyses were based on injury severity ( GCS ) at r and omisation and on time from injury to r and omisation . Analysis was by intention to treat . Effects on outcomes within 2 weeks of r and omisation are presented in this report . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N74459797 . FINDINGS Compared with placebo , the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids ( 1052 [ 21.1 % ] vs 893 [ 17.9 % ] deaths ; relative risk 1.18 [ 95 % CI 1.09 - 1.27 ] ; p=0.0001 ) . The relative increase in deaths due to corticosteroids did not differ by injury severity ( p=0.22 ) or time since injury ( p=0.05 ) . INTERPRETATION Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury . The cause of the rise in risk of death within 2 weeks is unclear Postal question naires are frequently used in research . One way of improving response rates is to use lotteries , although the evidence for their effectiveness is equivocal.1 - 4 An alternative , or complementary , approach to using lotteries is to make direct payments to survey responders . Few trials have evaluated direct payment compared with lotteries.3 Question naires about menopause services in the North West of Engl and were sent to a r and om sample of 1000 women aged 40 to 65 during September to November 1997 . The question naires included questions about use of hormone replacement therapy ( HRT ) and women 's demographic characteristics . The sample of women were r and omised in a 2 × 2 factorial trial to estimate the effectiveness of the two forms of incentive and their potential interaction within a single study . Unequal r and omisation of 3 to 1 favouring no direct payment was used to minimise research costs , which led This study tested the ability of nicotine to alleviate the tobacco withdrawal syndrome . Signs and symptoms of tobacco withdrawal were measured in 100 smokers who fulfilled DSM-III criteria for tobacco dependence and a past history of tobacco withdrawal . After 2 evenings of baseline measurement , subjects were r and omly assigned to receive either nicotine or placebo gum in a double blind manner . Subjects then stopped smoking , chewed gum freely , and returned on the 1st , 2nd , and 4th evenings of abstinence for further measurement . Nicotine reduced the increase in irritability , anxiety , difficulty concentrating , restlessness , impatience , and somatic complaints that subjects reported after cessation . Reductions in these withdrawal symptoms by nicotine were confirmed by ratings of significant others and by subjects ' scores on the Profile of Mood States . Nicotine did not reduce the increases in cigarette craving , hunger , eating , insomnia , tremulousness , or supine heart rate after cessation . The effects of nicotine occurred immediately and persisted throughout the study . Although many subjects correctly identified their drug group , the efficacy of the gum was independent of subjects ' identification s of drug . The relief of tobacco withdrawal by nicotine gum suggests that the tobacco withdrawal syndrome is caused , in part , by nicotine deprivation OBJECTIVE To assess the effect of electronic reminders ( ERs ) on response rate and time to response for the return of postal question naires . STUDY DESIGN AND SETTING This open r and omized controlled trial ( RCT ) was conducted at the University of York . Participants who were taking part in an established RCT and who provided an electronic mail address and /or mobile telephone number were eligible to take part in the study . The intervention group received ERs on the day they were expected to receive postal question naires . RESULTS One hundred forty-eight participants ( 19 male and 129 female ) aged 47±11 ( range , 19 - 65 ) years were studied . About 89.2 % of participants returned postal question naires . There was no difference in question naire response rates in control ( 64 of 74 [ 86.5 % ] ) vs. intervention ( 68 of 74 [ 91.9 % ] ) , groups ( relative risk=1.063 , 95 % confidence interval : 0.949 - 1.189 ) . Median question naire time to response was 4 days less in the intervention group ( 10.0±0.2 ; range , 10 - 14 days ) compared with the control group ( 14.0±1.4 ; range , 10 - 23 days ) ( χ(2)(1df)=5.27 , P=0.022 ) . CONCLUSION ERs are useful tools for reducing participant time to response for postal question naires . We found little evidence for an effect of ERs on response rate for postal question naires Mailed question naires are an economical method of data collection for epidemiologic studies , but response tends to be lower than for telephone or personal interviews . As part of a follow-up study of volunteers who provided a brief health history and blood sample for a blood specimen bank in 1989 , the authors conducted a controlled trial of the effect of length , incentives , and follow-up techniques on response to a mailed question naire . Interventions tested included variations on length of the question naire , effect of a monetary incentive , and effect of a postcard reminder versus a letter accompanied by a second question naire . Response was similar for the short ( 16-item , 4-page ) and long ( 76-item , 16-page ) question naire groups . The non-monetary [ corrected ] incentive did not improve the frequency of response . The second mailing of a question naire was significantly better than a postcard reminder in improving responses ( 23 % vs. 10 % ) . It is important to systematic ally test marketing principles to determine which techniques are effective in increasing response to mailed question naires for epidemiologic studies The impact of a disease on health related quality of life is important but difficult to measure . If the instrument used for measuring this is too complicated some people may not answer some questions and others may not respond at all . Although incomplete data may introduce biases , make interpretation difficult , and reduce the generalisability of the results , 1 papers on selecting quality of life instruments have ignored response frequency.2 ( 2 , 3 ) We postulated that the brevity and simplicity of the EuroQol question naire ( six separate questions and a visual analogue scale ) would achieve a better response in stroke survivors than the SF-36 ( 34 separate questions ) and performed a r and omised controlled trial to test this hypothesis . We included all patients who had been entered by United Kingdom centres in the International Stroke Trial between 2 March 1993 and 31 May 1995 who were not known Abstract Seventy-two overweight adult women who completed a 10 week course of behavioral self-management treatment for obesity were assigned to one of three 6 month long follow-up conditions : minimal contact , monitoring minimal contact , and continued contact via bimonthly groups . Subjects were assessed at weeks 0 , 10 , 18 , 26 , 34 and 52 . Subjects lost significant amounts of weight during treatment ( weeks 0–10 ) . At the end of the first 2 months of follow-up manipulations ( week 18 ) , the continued contact subjects had lost significantly more weight than minimal contact in terms of both pounds and percent overweight . Differences between the three groups were marginally significant at 4 months ( week 26 ) and percent overweight lost was significant at 6 months ( week 34 ) . At 52 weeks from study start differences no longer approached significance . When the two follow-up support conditions ( continued contact and monitoring/minimal contact ) were combined , differences between the follow-up support conditions combined and minimal contact were significant at 18 , 26 and 34 weeks from study start , but not at 52 weeks . Mood disturbance and health impairment were found to be correlated with weight loss Study sample Power calculations were used to determine the sample size . A 1300-patient sample would demonstrate a 10 % absolute difference ( 0.01 significance , 90 % power ) , and have an evens chance of identifying a 5 % difference at the 0.05 significance level . A total of 1,307 patients were eligible for inclusion in the study . A total of 654 patients were r and omly included in the intervention group , and 653 were r and omly allocated to the control group Patient surveys are commonly distributed at the end of a multicenter clinical trial . This Antiarrhythmics Versus Implantable Defibrillators ( AVID ) sub study prospect ively explored the relationship between methods used in distributing a survey and the quantity of responses received . AVID was a multicenter , r and omized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators . At study termination , a patient satisfaction survey was mailed to the 664 surviving participants . Questions included reasons for study participation , study benefits and problems and quality of care . Survey mailings were stratified by four factors in a 2x2x2x2 factorial design : delivery mode ( overnight vs. regular mail ) , certificate of appreciation , timing of administration ( " early " vs. " late " ) and cover letter signed by a physician versus coordinator . Patients were r and omly assigned to received one of 16 combinations of these four factors . Clinical characteristics and response rates were evaluated . Patients were more likely to return surveys delivered by overnight mail ( 75 % vs. 68 % , p=0.04 ) , with no certificate of appreciation enclosed ( 75 % vs. 68 % , p=0.05 ) and administered close to the time of study closeout ( 79 % vs. 72 % , p=0.085 ) . Compared to the 184 nonrespondents , the 456 ( 71 % ) respondents were older , Caucasian , lived with others , were high school graduates and less likely to have Medicare/Medicaid or HMO insurance ( p<0.03 ) . Physician recommendation was the most common reason cited for trial participation . Main benefits included increased knowledge of their medical condition and improved health . Reported problems included parking , transportation and excess clinic wait time . This r and omized study demonstrated that methods of patient survey distribution affect the survey return rate . Additional studies should explore mechanisms for maximizing return rates Women are disproportionately affected by the sexually transmitted infections ( STI ) epidemic , with African-Americans and Latinos at significantly higher risk for STIs than Caucasians . Successful recruitment and retention strategies used with young minority women in community-based STI prevention or intervention research have not been previously reported . This communication presents eight key strategies learned in the recruitment and retention of 16- to 21-year-old urban women participating in a 12-month r and omized clinical trial design ed to promote STI screening to decrease the duration of untreated chlamydia and gonorrhea infection . Strategies learned include : ( 1 ) Educate clinic staff on the rigors of study design ; ( 2 ) Facilitate a team effort between clinical and research staff ; modify recruitment procedures , as needed ; ( 3 ) Provide prospect i ve participants the option of enrolling by return appointment ; ( 4 ) Anticipate a diminishing recruitment pool over time ; ( 5 ) Set positive recruitment tone at the beginning of each clinic session ; ( 6 ) Consider participants ' mothers as important points of contact ; ( 7 ) Match communication styles to participant contacts ; and ( 8) Consider a variety of retention techniques . Together , these strategies helped to reinforce participant 's commitment to the project , facilitated their attendance at interviews , and encouraged them to adhere to the treatment protocol Background Attrition , or dropout , is a problem faced by many online health interventions , potentially threatening the inferential value of online r and omized controlled trials . Objective In the context of a r and omized controlled trial of an online weight management intervention , where 85 % of the baseline participants were lost to follow-up at the 12-month measurement , the objective was to examine the effect of nonresponse on key outcomes and explore ways to reduce attrition in follow-up surveys . Methods A sample of 700 nonrespondents to the 12-month online follow-up survey was r and omly assigned to a mail or telephone nonresponse follow-up survey . We examined response rates in the two groups , costs of follow-up , reasons for nonresponse , and mode effects . We ran several logistic regression models , predicting response or nonresponse to the 12-month online survey as well as predicting response or nonresponse to the follow-up survey . Results We analyzed 210 follow-up respondents in the mail and 170 in the telephone group . Response rates of 59 % and 55 % were obtained for the telephone and mail nonresponse follow-up surveys , respectively . A total of 197 respondents ( 51.8 % ) gave reasons related to technical issues or email as a means of communication , with older people more likely to give technical reasons for noncompletion ; 144 ( 37.9 % ) gave reasons related to the intervention or the survey itself . Mail follow-up was substantially cheaper : We estimate that the telephone survey cost about US $ 34 per sample d case , compared to US $ 15 for the mail survey . The telephone responses were subject to possible social desirability effects , with the telephone respondents reporting significantly greater weight loss than the mail respondents . The respondents to the nonresponse follow-up did not differ significantly from the 12-month online respondents on key outcome variables . Conclusions Mail is an effective way to reduce attrition to online surveys , while telephone follow-up might lead to overestimating the weight loss for both the treatment and control groups . Nonresponse bias does not appear to be a significant factor in the conclusions drawn from the r and omized controlled trial Background R and omised controlled trials often rely on question naires for follow-up . Objective To compare response rates to an online and postal 12-month follow-up question naire on sexual health in female students who took part in a chlamydia screening trial . Methods 1329 sexually active female students aged 16–27 were recruited from 12 universities and further education ( FE ) colleges . The 299 participants recruited between September 2004 and February 2005 were sent a postal question naire after 12 months . The 1030 participants recruited between March and December 2005 were contacted by email after 12 months and given a weblink to an online question naire . Results The response rates to the 12-month question naire in the online and postal groups were 51 % and 29 % 4 weeks after follow-up commenced ( RR 1.78 ( 1.47 to 2.14 ) ) and 72 % and 59 % after 3 months . After adjusting for ethnicity , smoking , type of educational institution ( university or FE college ) and subject studied ( health-related or not ) , the RR at 4 weeks was 1.88 ( 1.42 to 2.50 ) . However , a prior telephone call to confirm contact details increased the response rate at 3 months in the postal group . In the online group , university students , those of white ethnicity and non-smokers had higher response rates at 4 weeks . Conclusions In this young student population , an online question naire was quicker , cheaper and more efficient than a postal question naire . However , some FE college students did not have an email address . Telephone prompts and postal question naires were essential in obtaining a good response rate Objectives : Low response rates to postal question naires can threaten the validity of studies by reducing the effective sample size and introducing bias . The identification of methods with which to optimise response rates could , therefore , improve the quality of studies . In an attempt to identify such methods , we undertook a r and omised trial of two simple variations in question naire design . Methods : Using a 2 × 2 factorial design , we conducted a r and omised trial to test two variations in question naire design ; the question naires were printed on either single-sided or double-sided paper and had either a single- or multiple-booklet layout . Using equal r and om allocation , 3836 women were r and omised to receive one of these question naires as part of a study investigating risk factors for osteoporotic fractures . Results : One thous and eight hundred and seventy question naires were returned , giving an overall response rate of 48.7 % . There were no significant differences in the overall response to each of the four question naire design s. When the number of responders who completed at least 50 % of each of the three sections was identified , it was found that single-booklet question naires had a better response than the multiple-booklet question naires and that single-sided question naires had a better response than double-sided question naires . However , these results were not significant at the 5 % level . There were no significant differences in the response to questions on the odd ( left-h and side ) pages for the single- compared with the double-sided question naires . Conclusion : As the most cost-effective use of re sources , we would advocate the use of double- rather than single-sided question naires , and use of a single- rather than multiple-booklet design OBJECTIVES This study examined two major methadone treatment factors , visit frequency and methadone dose , posited to be important in reducing intravenous drug use and human immunodeficiency virus ( HIV ) transmission . METHODS One hundred fifty opiate-dependent subjects r and omly assigned to four groups received 50 or 80 mg of methadone and attended a clinic 2 or 5 days per week . RESULTS Survival analysis indicated higher dropout rates for groups having five vs two visits per week ( Chi2[1]=7.76 ) . Higher proportions of opiate-positive results on urine screens were associated with lower methadone doses ( F[1,91]=4.74 ) . CONCLUSIONS Receiving take-home doses early in treatment enhanced treatment retention . The 50-mg dose combined with five visits per week produced the worst outcome . Fewer visits enhanced retention at 50 mg , but opiate use rates were higher at this dose than they were for either 80-mg group . The HIV infection rate at entry was 9 % . No subjects seroconverted during the study . Risk behaviors for acquired immunodeficiency syndrome declined over time regardless of group/dose assignment . These results have important implication s for modification of regulatory and clinic policy changes Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial To assess whether changing the layout of the SF-12 affected item response rates , we tested two SF-12 formats in a quasi-r and omized trial of women aged > or=70 years in two general practice s in North Yorkshire . The modified version of the SF-12 ( ' York SF-12 ' ) converted the ' stem and leaf ' format of some questions to individual items . We assessed the effect of the two types of question naires on item response rates . The difference in overall response rates to the two question naires ( York SF-12 26.8 % ; SF-12 29.5 % ) was not statistically significant ( 95%CI -1.88 % to 7.22 % ) . However , the modified SF-12 had a statistically significantly lower item non-response rate of 8.5 % , compared with the 26.6 % of the SF-12 ( 95%CI 11.1%-25.1 % ) . Chronbach 's alpha reliability scores for the York SF-12 were also slightly better than for the older version . The York version of the SF-12 is an improvement on the original question naire . We recommend that the York SF-12 be used in preference to the SF-12 when surveying an older population BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people OBJECTIVES To compare clinicians ' choice of one of the st and ard epilepsy drug treatments ( carbamazepine or valproate ) versus appropriate comparator new drugs . DESIGN A clinical trial comprising two arms , one comparing new drugs in carbamazepine and the other with valproate . SETTING A multicentre study recruiting patients with epilepsy from hospital outpatient clinics . PARTICIPANTS Patients with an adequately documented history of two or more clinical ly definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option . INTERVENTIONS Arm A was carbamazepine ( CBZ ) versus gabapentin ( GBP ) versus lamotrigine ( LTG ) versus oxcarbazepine ( OXC ) versus topiramate ( TPM ) . Arm B valproate ( VPS ) versus LTG versus TPM . MAIN OUTCOME MEASURES Time to treatment failure ( withdrawal of the r and omised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two ) and time to achieve a 12-month remission of seizures . Time from r and omisation to first seizure , 24-month remission of seizures , incidence of clinical ly important adverse events , quality of life ( QoL ) outcomes and health economic outcomes were also considered . RESULTS Arm A recruited 1721 patients ( 88 % with symptomatic or cryptogenic partial epilepsy and 10 % with unclassified epilepsy ) . Arm B recruited 716 patients ( 63 % with idiopathic generalised epilepsy and 25 % with unclassified epilepsy ) . In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC . Some 12 % and 8 % fewer patients experienced treatment failure on LTG than CBZ , the st and ard drug , at 1 and 2 years after r and omisation , respectively . The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinical ly inferior to CBZ for measures of its efficacy . No consistent differences in QoL outcomes were found between treatment groups . Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality -adjusted life-year gained . In Arm B for time to treatment failure , VPS , the st and ard drug , was preferred to both TPM and LTG , as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission . QoL assessment s did not show any between-treatment differences . The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy , although there is a suggestion that TPM is a cost-effective alternative to VPS . CONCLUSIONS The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing st and ard drug treatment , CBZ , for patients diagnosed as having partial seizures . For patients with idiopathic generalised epilepsy or difficult to classify epilepsy , VPS remains the clinical ly most effective drug , although TPM may be a cost-effective alternative for some patients . Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy ( levetiracetam , zonisamide and pregabalin ) , therefore these drugs should be compared in a similarly design ed trial Abstract Overweight adult subjects were given a 12-week course in self-management training , and then divided into three 12-week follow-up conditions : booster ( continued contact plus monitoring ) , monitoring-only , and no-contact . The dependent variable was the Weight Reduction Ratio . At the end of the first 12-week period , treated subjects lost more weight than a no-treatment group of similar subjects . At the end of the second 12-week period , monitoring-only subjects continued to lose weight , and differed significantly from no-contact subjects . Booster subjects did not differ significantly from either of the other two groups ; however , when only those booster subjects who continued with the same therapist were considered , differences between no-contact and booster reached significance . Results are discussed in terms of the contributions of therapist contact and self-monitoring to produce the continued weight losses observed in this study Background A substantial proportion of patients with whiplash injuries develop chronic symptoms . However , the best treatment of acute injuries to prevent long-term problems is uncertain . A stepped care treatment pathway has been proposed , in which patients are given advice and education at their initial visit to the emergency department ( ED ) , followed by review at three weeks and physiotherapy for those with persisting symptoms . MINT is a two-stage r and omised controlled trial to evaluate two components of such a pathway : 1 . use of The Whiplash Book versus usual advice when patients first attend the emergency department ; 2 . referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks . Methods Evaluation of the Whiplash Book versus usual advice uses a cluster r and omised design in emergency departments of eight NHS Trusts . Eligible patients are identified by clinicians in participating emergency departments and are sent a study question naire within a week of their ED attendance . Three thous and participants will be included . Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually r and omised study of physiotherapy versus reinforcement of the advice given in ED . Six hundred participants will be r and omised . Follow-up is at 4 , 8 and 12 months after their ED attendance . Primary outcome is the Neck Disability Index ( NDI ) , and secondary outcomes include quality of life and time to return to work and normal activities . An economic evaluation is being carried out . Conclusion This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments , evaluating two components of a stepped-care approach to the treatment of whiplash injuries . The trial uses two r and omisations , with the first stage being cluster r and omised and the second individually r and omised Background Excessive alcohol consumption is a significant public health problem throughout the world . Although there are a range of effective interventions to help heavy drinkers reduce their alcohol consumption , these have little proven population -level impact . Research ers internationally are looking at the potential of Internet interventions in this area . Methods / Design In a two-arm r and omised controlled trial , an on-line psychologically enhanced interactive computer-based intervention is compared with a flat , text-based information web-site . Recruitment , consent , r and omisation and data collection are all on-line . The primary outcome is total past-week alcohol consumption ; secondary outcomes include hazardous or harmful drinking , dependence , harm caused by alcohol , and mental health . A health economic analysis is included . Discussion This trial will provide information on the effectiveness and cost-effectiveness of an on-line intervention to help heavy drinkers drink less . Trial registration International St and ard R and omised Controlled Trial Number Register IS RCT BACKGROUND Preterm , prelabour rupture of the fetal membranes ( pPROM ) is the commonest antecedent of preterm birth , and can lead to death , neonatal disease , and long-term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate , but the results were inconclusive . We did a r and omised multicentre trial to try to resolve this issue . METHODS 4826 women with pPROM were r and omly assigned 250 mg erythromycin ( n=1197 ) , 325 mg co-amoxiclav ( 250 mg amoxicillin plus 125 mg clavulanic acid ; n=1212 ) , both ( n=1192 ) , or placebo ( n=1225 ) four times daily for 10 days or until delivery . The primary outcome measure was a composite of neonatal death , chronic lung disease , or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS Two women were lost to follow-up , and there were 15 protocol violations . Among all 2415 infants born to women allocated erythromycin only or placebo , fewer had the primary composite outcome in the erythromycin group ( 151 of 1190 [ 12.7 % ] vs 186 of 1225 [ 15.2 % ] , p=0.08 ) than in the placebo group . Among the 2260 singletons in this comparison , significantly fewer had the composite primary outcome in the erythromycin group ( 125 of 1111 [ 11.2 % ] vs 166 of 1149 [ 14.4 % ] , p=0.02 ) . Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only . Use of erythromycin was also associated with prolongation of pregnancy , reductions in neonatal treatment with surfactant , decreases in oxygen dependence at 28 days of age and older , fewer major cerebral abnormalities on ultrasonography before discharge , and fewer positive blood cultures . Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy , they were also associated with a significantly higher rate of neonatal necrotising enterocolitis . INTERPRETATION Erythromycin for women with pPROM is associated with a range of health benefits for the neonate , and thus a probable reduction in childhood disability . However , co-amoxiclav can not be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis . A follow-up study of childhood development and disability after pPROM is planned |
516 | 24,998,515 | Effectiveness was demonstrated across three distinct functions that emerged from the data : accessing information for clinical knowledge , adherence to guidelines and diagnostic decision making .
When healthcare professionals used h and held computers to access clinical information , their knowledge improved significantly more than peers who used paper re sources .
When clinical guideline recommendations were presented on h and held computers , clinicians made significantly safer prescribing decisions and adhered more closely to recommendations than peers using paper re sources .
Finally , healthcare professionals made significantly more appropriate diagnostic decisions using clinical decision making tools on h and held computers compared to colleagues who did not have access to these tools .
Conclusion Healthcare professionals ’ use of h and held computers may improve their information seeking , adherence to guidelines and clinical decision making .
H and held computers can provide real time access to and analysis of clinical information .
The integration of clinical decision support systems within h and held computers offers clinicians the highest level of synthesis ed evidence at the point of care . | Background Many healthcare professionals use smartphones and tablets to inform patient care .
Contemporary research suggests that h and held computers may support aspects of clinical diagnosis and management .
This systematic review was design ed to synthesis e high quality evidence to answer the question ; Does healthcare professionals ’ use of h and held computers improve their access to information and support clinical decision making at the point of care ? | OBJECTIVE This study assessed the effect of a h and held computer-based decision support system ( DSS ) on antibiotic use and patient outcomes in a critical care unit . DESIGN A DSS containing four types of evidence ( patient microbiology reports , local antibiotic guidelines , unit-specific antibiotic susceptibility data for common bacterial pathogens , and a clinical pulmonary infection score calculator ) was developed and implemented on a h and held computer for use in the intensive care unit at a tertiary referral hospital . System impact was assessed in a prospect i ve " before/after " cohort trial lasting 12 months . Outcome measures were defined daily doses ( DDDs ) of antibiotics per 1,000 patient-days , patient length of stay , and mortality . RESULTS The number of admissions , APACHE ( Acute Physiology , Age , and Chronic Health Evaluation ) II and SAPS ( Simplified Acute Physiology Score ) II for patients in preintervention , and intervention ( DSS use ) periods were statistically comparable . The mean patient length of stay and the use of antibiotics in the unit during six months of the DSS use decreased from 7.15 to 6.22 bed-days ( p = 0.02 ) and from 1,767 DDD to 1,458 DDD per 1,000 patient-days ( p = 0.04 ) , respectively , with no change in mortality . The DSS was accessed 674 times during 168 days of the trial . Microbiology reports and antibiotic guidelines were the two most commonly used ( 53 % and 22.5 % , respectively ) types of evidence . The greatest reduction was observed in the use of beta-lactamase-resistant penicillins and vancomycin . CONCLUSION H and held computer-based decision support contributed to a significant reduction in patient length of stay and antibiotic prescribing in a critical care unit The purpose of the study was to compare the proportion of obesity-related diagnoses in clinical encounters ( N = 1874 ) documented by nurses using a personal digital assistant-based log with and without obesity decision support features . The experimental group encounters in the r and omized controlled trial had significantly more ( P = .000 ) obesity-related diagnoses ( 11.3 % ) than did the control group encounters ( 1 % ) and a significantly lower false negative rate ( 24.5 % vs 66.5 % , P = .000 ) . The study findings provide evidence that integration of a decision support feature that automatically calculates an obesity-related diagnosis increases diagnoses and decreases missed diagnoses and suggest that such systems have the potential to improve the quality of obesity-related care Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To evaluate the effectiveness of a personal digital assistant (PDA)-based clinical decision support system ( CDSS ) on nonsteroidal anti-inflammatory drug ( NSAID ) prescribing safety in the outpatient setting . DESIGN The design was a r and omized , controlled trial conducted in a university-based resident clinic . Internal medicine residents received a PDA-based CDSS suite . For intervention residents , the CDSS included a prediction rule for NSAID-related gastrointestinal risk assessment and treatment recommendations . Unannounced st and ardized patients ( SPs ) trained to portray musculoskeletal symptoms presented to study physicians . Safety outcomes were assessed from the prescriptions given to the SPs . Each prescription was review ed by a committee of clinicians blinded to participant , intervention group assignment , and baseline or follow-up status . MEASUREMENTS Prescriptions were judged as safe or unsafe . The main outcome measure was the differential change in unsafe prescribing of NSAIDs for the intervention versus the control group . RESULTS At baseline , the mean proportion of cases per physician with unsafe prescriptions for the two groups was similar ( 0.27 vs. 0.29 , p > 0.05 ) . Controlling for baseline performance , intervention participants prescribed more safely than controls after receiving the CDSS ( 0.23 vs. 0.45 [ F = 4.24 , p < 0.05 ] ) . With the CDSS , intervention participants documented more complete assessment of patient gastrointestinal risk from NSAIDs . CONCLUSION PARTICIPANTS provided with a PDA-based CDSS for NSAID prescribing made fewer unsafe treatment decisions than participants without the CDSS Summary Background Health workers ' malaria case-management practice s often differ from national guidelines . We assessed whether text-message reminders sent to health workers ' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya . Methods From March 6 , 2009 , to May 31 , 2010 , we did a cluster-r and omised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya . With a computer-generated sequence , health facilities were r and omly allocated to either the intervention group , in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months , or the control group , in which health workers did not receive any text messages . Health workers were not masked to the intervention , although patients were unaware of whether they were in an intervention or control facility . The primary outcome was correct management with artemether-lumefantrine , defined as a dichotomous composite indicator of treatment , dispensing , and counselling tasks concordant with Kenyan national guidelines . The primary analysis was by intention to treat . The trial is registered with Current Controlled Trials , IS RCT N72328636 . Findings 119 health workers received the intervention . Case-management practice s were assessed for 2269 children who needed treatment ( 1157 in the intervention group and 1112 in the control group ) . Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points ( 95 % CI 7·6–40·0 ; p=0·004 ) immediately after intervention and by 24·5 percentage-points ( 8·1–41·0 ; p=0·003 ) 6 months later . Interpretation In re source -limited setting s , malaria control programmes should consider use of text messaging to improve health workers ' case-management practice s. Funding The Wellcome Trust OBJECTIVE To examine whether Palm Prevention , a free software tool for Palm OS personal digital assistants ( PDAs ) that provides quick access to preventive guidelines in a patient-specific manner at the point of care , improved adherence to five preventive measures in primary care . DESIGN Prospect i ve intervention pilot study . SETTING Vancouver , BC , and surrounding area . PARTICIPANTS Eight general practitioners . INTERVENTIONS Each physician used Palm Prevention for five preventive measures during routine preventive health visits with 10 patients ( n = 80 ) . Charts of consenting patients were review ed for documentation of recommended maneuvers . MAIN OUTCOME MEASURES Rates of adherence to five evidence -based guidelines selected from the Canadian and American task forces on preventive care and incorporated into Palm Prevention . RESULTS Intervention and control physicians were similar in their familiarity with and use of PDAs , and they recruited similar patients for the study . Intervention and control groups had similar rates of screening for hypertension . Intervention improved adherence to the remaining four guidelines : cervical cancer screening increased 22 % ( only absolute increases are reported ) ; hyperlipidemia screening increased 30 % ; colorectal cancer screening increased 27 % ; and prophylaxis with acetylsalicylic acid in high-risk patients increased 38 % . Participants were surveyed after the study ; all reported that they found the software helpful and would continue using Palm Prevention . Usage statistics showed that study participants used the tool outside the trial : users entered between 28 and 68 unique patients into the program during the 2-month intervention . CONCLUSION This pilot study suggests PDAs are useful in improving preventive care and facilitating translation of knowledge into practice . This was particularly apparent with newer guidelines OBJECTIVE Personal digital assistants ( PDAs ) are popular with physicians : in 2003 , 33 % of Canadian doctors reported using them in their practice s. We do not know , however , whether using a PDA changes the behaviour of practising physicians . We studied the effectiveness of a PDA software application to help family physicians diagnose angina among patients with chest pain . DESIGN Prospect i ve r and omized controlled pilot trial using a cluster design . SETTING Primary care practice s in the Toronto area . PARTICIPANTS Eighteen family physicians belonging to the North Toronto Primary Care Research Network ( Nortren ) or recruited from a local hospital . INTERVENTIONS We r and omized physicians to receive a Palm PDA ( which included the angina diagnosis software ) or to continue conventional care . Physicians prospect ively recorded the process of care for patients aged 30 to 75 presenting with suspected angina , over 7 months . MAIN OUTCOME MEASURES Did the process of care for patients with suspected angina improve when their physicians had PDAs and software ? The primary outcomes we looked at were frequency of cardiac stress test orders for suspected angina , and the appropriateness of referral for cardiac stress testing at presentation and for nuclear cardiology testing after cardiac stress testing . Secondary outcome was referrals to cardiologists . RESULTS The software led to more overall use of cardiac stress testing ( 81 % vs 50 % ) . The absolute increase was 31 % ( P = .007 , 95 % confidence interval [ CI ] 8 % to 58 % ) . There was a trend toward more appropriate use of stress testing ( 48.6 % with the PDA vs 28.6 % control ) , an increase of 20 % ( P = .284 , 95 % CI -11.54 % to 51.4 % ) . There was also a trend toward more appropriate use of nuclear cardiology following cardiac stress testing ( 63.0 % vs 45.5 % ) , an absolute increase of 17.5 % ( P = .400 , 95 % CI -13.9 % to 48.9 % ) . Referrals to cardiologists did not increase ( 38.2 % with the PDA vs 40.9 % , P = .869 ) . CONCLUSION A PDA-based software application can lead to improved care for patients with suspected angina seen in family practice s ; this finding requires confirmation in a larger study OBJECTIVE To assess the acceptability and usage of a st and alone personal digital assistant (PDA)-based clinical decision-support system ( CDSS ) for the diagnosis and management of acute respiratory tract infections ( RTIs ) in the outpatient setting . DESIGN Observational study performed as part of a larger r and omized trial in six rural communities in Utah and Idaho from January 2002 to March 2004 . Ninety-nine primary care providers received a PDA-based CDSS for use at the point-of-care , and were asked to use the tool with at least 200 patients with suspected RTIs . MEASUREMENTS Clinical data were collected electronically from the devices at periodic intervals . Providers also completed an exit question naire at the end of the study period . RESULTS Providers logged 14,393 cases using the CDSS , the majority of which ( n=7624 ; 53 % ) were from family practitioners . Overall adherence with CDSS recommendations for the five most common diagnoses ( pharyngitis , otitis media , sinusitis , bronchitis , and upper respiratory tract infection ) was 82 % . When antibiotics were prescribed ( 53 % of cases ) , adherence with the CDSS-recommended antibiotic was high ( 76 % ) . By logistic regression analysis , the odds of adherence with CDSS recommendations increased significantly with each ten cases completed ( P=0.001 ) . Question naire respondents believed the CDSS was easy to use , and most ( 44/65 ; 68 % ) did not believe it increased their encounter time with patients , regardless of prior experience with PDAs . CONCLUSION A st and alone PDA-based CDSS for acute RTIs used at the point-of-care can encourage better outpatient antimicrobial prescribing practice s and easily gather a rich set of clinical data BACKGROUND Testing for pulmonary embolism often differs from that recommended by evidence -based guidelines . OBJECTIVE To assess the effectiveness of a h and held clinical decision-support system to improve the diagnostic work-up of suspected pulmonary embolism among patients in the emergency department . DESIGN Cluster r and omized trial . Assignment was by r and om-number table , providers were not blinded , and outcome assessment was automated . ( Clinical Trials.gov registration number : NCT00188032 ) . SETTING 20 emergency departments in France . PATIENTS 1103 and 1768 consecutive out patients with suspected pulmonary embolism . INTERVENTION After a preintervention period involving 20 centers and 1103 patients , in which providers grew accustomed to inputting clinical data into h and held devices and investigators assessed baseline testing , emergency departments were r and omly assigned to activation of a decision-support system on the devices ( 10 centers , 753 patients ) or posters and pocket cards that showed vali date d diagnostic strategies ( 10 centers , 1015 patients ) . MEASUREMENTS Appropriateness of diagnostic work-up , defined as any sequence of tests that yielded a posttest probability less than 5 % or greater than 85 % ( primary outcome ) or as strict adherence to guideline recommendations ( secondary outcome ) ; number of tests per patient ( secondary outcome ) . RESULTS The proportion of patients who received appropriate diagnostic work-ups was greater during the trial than in the preintervention period in both groups , but the increase was greater in the computer-based guidelines group ( adjusted mean difference in increase , 19.3 percentage points favoring computer-based guidelines [ 95 % CI , 2.9 to 35.6 percentage points ] ; P = 0.023 ) . Among patients with appropriate work-ups , those in the computer-based guidelines group received slightly fewer tests than did patients in the paper guidelines group ( mean tests per patient , 1.76 [ SD , 0.98 ] vs. 2.25 [ SD , 1.04 ] ; P < 0.001 ) . LIMITATION The study was not design ed to show a difference in the clinical outcomes of patients during follow-up . CONCLUSION A h and held decision-support system improved diagnostic decision making for patients with suspected pulmonary embolism in the emergency department BACKGROUND Use of electronic medical information re sources by health-care professionals is increasing . Portable h and held computers have facilitated access to medical knowledge at the point of patient care . Little is known about the impact of mobile medical information tools on physician learning or improvement in decision-making . STUDY DESIGN A 6-month prospect i ve , r and omized pilot study of 12 first-year trauma and critical care Fellows at the R Adams Cowley Shock Trauma Center was conducted from November 1 , 2001 to May 31 , 2002 at the University of Maryl and . Six Fellows were r and omized to use the Johns Hopkins Antibiotic Guide ( JHABX ) on the RIM Blackberry personal digital assistant ( PDA ) for 6 months of their clinical rotation . Six Fellows were r and omized to the non-PDA-use arm . Three-month and 6-month examination raw scores on knowledge of infectious diseases management among Blackberry PDA users versus non-PDA users were obtained . Measurement of antibiotic decision accuracy by diagnosis at 3 and 6 months among Fellows r and omized to use the JHABX on the RIM Blackberry PDA was also evaluated . RESULTS PDA group demonstrated a considerable improvement in test scores over the 3-month time interval , compared with their baseline score ( 40.8 + /- 2.3 versus 34.3 + /- 4.6 , p < 0.05 ) and compared with the non-PDA group ( 40.8 + /- 2.3 versus 36.8 + /- 3.3 , p < 0.01 ) . Improvement became even more notable at the 6-month interval again , compared with themselves ( 43.8 + /- 4.5 versus 34.3 , p < 0.001 ) and the non-PDA group ( 43.8 + /- 4.5 versus 38.1 + /- 5.1 , p < 0.001 ) . There was no notable improvement in test scores at 3 months or 6 months in the control group . Overall antibiotic decision accuracy substantially improved from 66 % during the initial 3-month period to 86.6 % during the second 3-month period ( p = 0.005 ) among users of the JHABX . This was most evident in respiratory , blood , and skin and soft tissue infections . CONCLUSIONS Web-based h and held technology is highly effective for supplying information to support infectious disease clinical practice . In a hospital intensive care setting , results of this study demonstrate that resident physician knowledge and antibiotic decision selection accuracy improved among Fellows using the JHABX . Reasons for this difference can be multifold and not thoroughly evaluated from this small pilot study . Future studies on the impact of point-of-care technology on patient outcomes are warranted |
517 | 18,308,891 | The relationship between adequate dynamic joint stability and efficient movement patterns are complex .
Adequate antagonistic co-contraction of hamstring musculature seems to be a component of all functional movements , possibly maintain dynamic knee stability and protect against excessive joint loads . | OBJECTIVES To systematic ally review the current literature that relates the effects of age and skill level to motor control patterns of knee musculature co-contraction during functional movements . | BACKGROUND Women have higher rates of knee ligament injury than men . Co-contraction of knee muscles is proposed to be an important mechanism to protect the joint from injuries . HYPOTHESIS Females have lower co-contraction levels when compared to males . STUDY DESIGN Exploratory , cross-sectional design . METHODS Thirty-six men and women equally divided into four groups according to gender and activity level ( sedentary and athletic ) were compared in relation to vastus lateralis and biceps femoris co-contraction before heel strike during level walking and before floor contact during l and ing from a jump . Muscular co-contraction was assessed by surface electromyography . Correlations between co-contraction and ligament laxity , extensor and flexor work , and flexion/extension torque ratio were also analyzed . RESULTS No differences between genders were found in the studied situations ( p0.381 ) . During walking , co-contraction was greater in sedentary women compared to athletic women ( p=0.002 ) . A moderate inverse correlation was found between co-contraction during walking and women extensor ( r=-0.613 ; p=0.007 ) and flexor ( r=-0.575 ; p=0.012 ) work . During l and ing from a jump , no variables correlated to co-contraction in any of the groups tested ( r0.477 ; p0.061 ) . CONCLUSION Co-contraction levels were not different between genders . Results suggest that women compensate strength deficits by means of increasing activation levels , possibly to generate adequate joint stiffness to meet stabilization dem and s. However , this is not evident in a more stressful activity like l and ing from a jump . CLINICAL RELEVANCE This study contributes to a better underst and ing of the factors related to joint protection in females , who are at a greater risk of ligament injuries BACKGROUND Despite recent evidence supporting the use of neuromuscular training to reduce anterior cruciate ligament injury risk , female athletes continue to show an increased anterior cruciate ligament injury rate in collegiate basketball and soccer when compared to males . The purpose of the current study was to identify gender and task differences in measures that may increase the risk of anterior cruciate ligament injury in female basketball and soccer athletes . METHODS Eleven female and 11 male collegiate basketball and soccer athletes were height ( female mean 176 ( SD 8 cm ) , male mean 176 ( SD 8 cm ) ) and weight ( female mean 73 ( SD 7 kg ) , male mean 74 ( SD 6 kg ) ) matched . Three-dimensional motion analysis was used to calculate differences in total coronal plane angular joint excursion ( maximum-minimum ) between male and female athletes when performing a series of medially and laterally directed drop l and ings . FINDINGS Female athletes demonstrated increased total coronal plane excursion for the hip , knee and ankle ( P < 0.05 ) during the medial drop l and ing . During the lateral drop l and ing females displayed increased excursion at the hip and knee . When comparing tasks , the lateral drop l and ing result ed in greater coronal plane excursion at the hip ( P < 0.05 ) while the knee showed no differences between movements . In contrast , females demonstrated increased ankle excursion during the medial drop task ( P < 0.05 ) . INTERPRETATION Female athletes demonstrate increased lower extremity coronal plane excursion when performing single leg drop l and ing in both the medial and lateral direction when compared to height/weight matched male athletes . This increased coronal plane oscillation of lower extremity joints may be related to the increased risk of anterior cruciate ligament injury for female basketball and soccer athletes BACKGROUND It is thought that female athletes with limited experience in a sport perform athletic maneuvers differently than their more experienced counterparts , and that they do so in a manner that places them at greater risk for injury . The purpose of this study was to evaluate the influence of athletic experience on knee mechanics during the execution of a side-step cutting maneuver in young female athletes . METHODS Three-dimensional kinematics , ground reaction forces and electromyographic activity ( surface electrodes ) were recorded during the early deceleration phase of side-step cutting in 30 high school females ( 15 experienced , 15 novice ) . Group differences in knee joint kinematics , peak moments , net joint moment impulse and average muscle activation were evaluated . FINDINGS No significant group differences were found in knee kinematics . When compared to experienced females , novice females demonstrated significantly smaller flexor , adductor , and internal rotator peak moments and smaller net joint moment impulse in all three planes at the knee . No group differences were found for average EMG ; however , novice athletes had significantly greater co-contraction at the knee . INTERPRETATION The finding of smaller knee moments and greater muscle co-contraction in the novice group suggests that these athletes may adopt a protective strategy in response to a relatively unfamiliar task . In addition , these results suggest that increased moments at the knee emerge with experience , indicating that more skilled athletes may be at greater risk for anterior cruciate ligament ( ACL ) injury BACKGROUND AND PURPOSE Dynamic knee stabilization strategies of people who successfully compensate for the absence of an anterior cruciate ligament ( ACL ) ( " copers " ) are different from those of people who do not compensate well for the injury ( " noncopers " ) . Early after injury , certain patients ( " potential copers " ) can increase the likelihood of successfully compensating for the injury by participating in 10 sessions of perturbation training . The purpose of this study was to determine how perturbation training alters muscle co-contraction and knee kinematics in potential copers . SUBJECTS Seventeen individuals with acute , unilateral ACL rupture who were categorized as potential copers and 17 subjects without injuries who were matched by age , sex , and activity level were recruited for this study . METHODS Motion analysis and electromyographic data were collected as subjects walked across a stationary or moving platform ( horizontal translation ) before and after perturbation training . RESULTS Before training , potential copers had higher co-contraction indexes and lower peak knee flexion angles than subjects without injuries . After training , potential copers ' movement patterns more closely resembled those of subjects without injuries ( ie , they showed reduced co-contraction indexes and increased peak knee flexion angles during stance ) . DISCUSSION AND CONCLUSION Perturbation training reduced quadriceps femoris-hamstring muscle and quadriceps femoris-gastrocnemius muscle co-contractions and normalized knee kinematics in individuals with ACL rupture who were classified as potential copers . Findings from this study provide evidence for a mechanism by which perturbation training acts as an effective intervention for promoting coordinated muscle activity in a select population of people with ACL rupture Background Female athletes participating in high-risk sports suffer anterior cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes . Hypothesis Prescreened female athletes with subsequent anterior cruciate ligament injury will demonstrate decreased neuromuscular control and increased valgus joint loading , predicting anterior cruciate ligament injury risk . Study Design Cohort study ; Level of evidence , 2 . Methods There were 205 female athletes in the high-risk sports of soccer , basketball , and volleyball prospect ively measured for neuromuscular control using 3-dimensional kinematics ( joint angles ) and joint loads using kinetics ( joint moments ) during a jump-l and ing task . Analysis of variance as well as linear and logistic regression were used to isolate predictors of risk in athletes who subsequently ruptured the anterior cruciate ligament . Results Nine athletes had a confirmed anterior cruciate ligament rupture ; these 9 had significantly different knee posture and loading compared to the 196 who did not have anterior cruciate ligament rupture . Knee abduction angle ( P < . 05 ) at l and ing was 8 ° greater in anterior cruciate ligament-injured than in uninjured athletes . Anterior cruciate ligament-injured athletes had a 2.5 times greater knee abduction moment ( P < . 001 ) and 20 % higher ground reaction force ( P < . 05 ) , whereas stance time was 16 % shorter ; hence , increased motion , force , and moments occurred more quickly . Knee abduction moment predicted anterior cruciate ligament injury status with 73 % specificity and 78 % sensitivity ; dynamic valgus measures showed a predictive r2 of 0.88 . Conclusion Knee motion and knee loading during a l and ing task are predictors of anterior cruciate ligament injury risk in female athletes . Clinical Relevance Female athletes with increased dynamic valgus and high abduction loads are at increased risk of anterior cruciate ligament injury . The methods developed may be used to monitor neuromuscular control of the knee joint and may help develop simpler measures of neuromuscular control that can be used to direct female athletes to more effective , targeted interventions |
518 | 22,531,088 | If sensation drives behavior , comprehensive data on the sensation of breathlessness might assist in underst and ing the behavioral consequences of interventions | Breathlessness on exertion is common in people with obesity .
Assessment s of breathlessness may include sensation ( intensity , sensory quality or unpleasantness ) and / or the behavioral/emotional consequences of the sensation ( respiratory-related functional impairment , disability or quality of life ) .
This systematic review of primary studies published since 2005 evaluated how has the sensation of breathlessness been assessed in adults with increased adiposity . | BACKGROUND Although question naires are used frequently with patients to self-report the severity of dyspnea as related to activities of daily living , the reliability of these instruments has not been established . The two purpose s of this study were to examine the test-retest reliability of three widely used dyspnea instruments and to compare dyspnea scores at different stages of disease . METHODS At paired baseline visits , 101 stable patients with COPD were tested ; at paired follow-up visits at 3 months , 89 of these patients were tested . At each visit , patients rated dyspnea with three instruments presented in r and om order and then performed post-bronchodilator therapy lung function tests . RESULTS Patient-reported dyspnea scores and lung function were similar at baseline ( interval , 6 + /- 5 days ) and follow-up visits ( interval , 4 + /- 2 days ) . Intraclass correlation coefficients at baseline and at follow-up were 0.82 and 0.82 , respectively , for the modified Medical Research Council scale ; 0.90 and 0.84 , respectively , for the self-administered computerized versions of the baseline dyspnea index and transition dyspnea indexes ; and 0.95 and 0.89 for the University of San Diego Shortness of Breath Question naire results . Dyspnea ratings were significantly related to the stage of disease severity based on percent predicted FEV(1 ) ( p < 0.001 ) . CONCLUSIONS Test-retest reliability was acceptable for patient-reported dyspnea scores using three clinical instruments at baseline and at the 3-month follow-up . Our results demonstrate for the first time that patient-reported dyspnea ratings are related to the stage of disease severity Reproducibility and validity are prerequisites for a useful clinical scale . We therefore prospect ively tested the reproducibility and validity of the New York Heart Association criteria and the Canadian Cardiovascular Society criteria for the assessment of cardiac functional class and compared these criteria with a new Specific Activity Scale based on the metabolic costs of specific activities . The New York Heart Association estimates made by two physicians had a reproducibility of only 56 % , and only 51 % of the estimates agreed with treadmill exercise performance . Functional estimates based on the Canadian Cardiovascular Society criteria were significantly more reproducible ( 73 % ) , but not significantly more valid . The Specific Activity Scale was as reproducible as the Canadian Cardiovascular Society criteria , and its 68 % validity was significantly higher than the validities of the other systems . The easily administered Specific Activity Scale was equally reproducible and valid when used by a nonphysician . It was especially better than the other systems for the evaluation of true class II patients and was significantly less likely to underestimate treadmill performance . Although no set of questions can perfectly predict exercise tolerance , the Specific Activity Scale deserves wider prospect i ve testing PURPOSE Overweight and obese subjects often perceive increased breathlessness during minor exertion and therefore avoid exercise . Respiratory muscle endurance training ( RMET ) can reduce the perception of breathlessness . We hypothesized that RMET 1 month before and during a 6-month ( 3 months supervised + 3 months unsupervised ) exercise and nutrition counseling program ( EN ) would improve the benefits of EN . METHODS Twenty-six overweight and obese subjects with significant perception of breathlessness during exercise ( age = 33 ± 9 yr , body mass index ( BMI ) = 31.3 ± 4.9 kg·m(-2 ) ) were r and omized to RMET+EN ( R+EN ) or EN alone . R+EN performed 30 min of normocapnic hyperpnea 5 wk(-1 ) before and 2 wk(-1 ) during EN . EN consisted of two strength and three endurance training sessions per week , as well as prescribed nutritional composition and a 2.1-kJ ( 500-kcal ) energy deficit per day . Both groups had an equal number of laboratory visits during the 7 months . Before and after 4 and 7 months , subjects performed a 12-min time trial ( TT ; 6 + 6 min , 2-min pause ) and an incremental cycling test ( ICT ) to exhaustion , and blood lipids were assessed . RESULTS Weight loss was significant and similar in both groups ( -4.2 vs -3.7 kg ; both P < 0.05 ) . During the first 4 months , distance covered in 12 min improved more ( P < 0.05 ) with R+EN ( 1678 vs 1824 m ; P < 0.001 ) than with EN alone ( 1638 vs 1698 m ; P < 0.05 ) , whereas after R+EN , breathlessness during the ICT was reduced . Blood lipids of the pooled group improved in those subjects with pathologic values before the study . Despite reduced training compliance during the unsupervised period , subjects of both groups maintained the benefits attained during the supervised period . CONCLUSIONS R+EN improved TT performance more than EN alone , despite similar weight loss , possibly owing to the reduced perception of breathlessness OBJECTIVE Our objective was to study the effects of physical training combined with dietary measures in obese adults . In a second step , we sought to compare two training protocol s and establish the additional contribution of strength training . METHODS We performed a r and omized , prospect i ve survey from July 2004 to November 2007 . Included patients were r and omized into three groups : a control group ( G1 ) , a group ( G2 ) performing dietary measures and a programme of treadmill training at 60 % of each individual 's maximum heart rate ( HRmax ) and a group ( G3 ) who followed the G2 programme supplemented with strength training . All patients underwent an initial and final assessment of anthropometric & cardiovascular parameters , muscle strength , dyspnoea during activities of daily living , metabolic disorders , psychological status and quality of life . RESULTS The greatest weight loss ( 7.24 % ) was observed in G3 . Reduction in waistline measurement ( WL ) of 4.3 % and 10.26 % were noted in G2 and G3 , respectively ( p < 0.001 ) . The percentage fat body mass fell by 10.4 % in G3 ( p < 0.001 ) and 8.6 % in G2 ( p = 0.03).We particularly noted an improvement in physical condition in groups 2 and 3 , with lower HR and blood pressure values at rest and at maximum effort . The overall improvement in both arm and leg muscle strength was greater for G3 than for G2 . Likewise , we noted an improvement in the metabolic parameters and depression & anxiety scores for the trained groups ( G2 , G3 ) , relative to the control group ( G1 ) . We also noted improvements in the total impact of weight on quality of life ( IWQOL ) lite score of 15.2 % in G2 and 18 % in G3 . CONCLUSION Our survey demonstrated the beneficial effect of combining dietary measures and physical training in obese patients . In addition to weight loss , the programme enabled a reduction in the patients ' body fat mass and abdominal obesity , a correction of metabolic disorders and an improvement in aerobic capacity . The improvement in all these parameters also enhanced the patients ' psychological status and quality of life . The addition of strength training produced notable improvements in weight loss , arm muscle strength and abdominal obesity We mimicked important mechanical and ventilatory aspects of restrictive lung disorders by employing chest wall strapping ( CWS ) and dead space loading ( DS ) in normal subjects to gain mechanistic insights into dyspnea causation and exercise limitation . We hypothesized that thoracic restriction with increased ventilatory stimulation would evoke exertional dyspnea that was similar in nature to that experienced in such disorders . Twelve healthy young men [ 28 + /- 2 ( SE ) yr of age ] completed pulmonary function tests and maximal cycle exercise tests under four conditions , in r and omized order : 1 ) control , 2 ) CWS to 60 % of vital capacity , 3 ) added DS of 600 ml , and 4 ) CWS + DS . Measurements during exercise included cardiorespiratory parameters , esophageal pressure , and Borg scale ratings of dyspnea . Compared with control , CWS significantly reduced the tidal volume response to exercise , increased dyspnea intensity at any given work rate or ventilation , and thus limited exercise performance . DS stimulated ventilation but had minimal effects on dyspnea and exercise performance . Adding DS to CWS further increased dyspnea by 1.7 + /- 0.6 st and ardized Borg units ( P = 0.012 ) and decreased exercise performance ( total work ) by 21 + /- 6 % ( P = 0.003 ) over CWS alone . Across conditions , increased dyspnea intensity correlated best with decreased resting inspiratory reserve volume ( r = -0.63 , P < 0.0005 ) . Dyspnea during CWS was described primarily as " inspiratory difficulty " and " unsatisfied inspiration , " similar to restrictive disorders . In conclusion , severe dyspnea and exercise intolerance were provoked in healthy normal subjects when tidal volume responses were constrained in the face of increased ventilatory drive during exercise BACKGROUND Maximal incremental exercise testing should be completed within 8 - 12 minutes . The ramp-slope influences the exercise duration . Oxygen-cost diagram ( OCD ) is a scoring scale for the capability of daily activity performed and therefore can be used to estimate the ramp-slope . METHODS The OCD-algorithm and the reported-algorithm were used prospect ively in r and om order for selecting optimal ramp-slope : Ramp-slope(OCD)=Score(OCD)xweight in kg/40 for men and weight/50 for women and Ramp-slope(reported)=(Predicted V(O2peak)-V(O2unloaded))/100 . Fifty-three dyspneic patients and 16 normal controls were enrolled to perform a ramp-pattern exercise . Fourteen patients not reaching maximum exercise levels were excluded . The exercise capacity , exercise time , and success rate of loaded exercise between 8 and 12 minutes were measured . RESULTS Comparing the reported-algorithm to the OCD-algorithm in normal controls , the only difference was that the ramp-slope was higher in males ; in patients , the ramp-slope was higher in males , the exercise time shorter and the success rate lower ( 8.6+/-3.3 vs. 9.4+/-2.1 min , 61.5 % vs. 84.6 % , both p<0.05 ) ; in obese patients , the ramp-slope was lower and the exercise time longer . CONCLUSION OCD score can predict the ramp-slope selection for exercise testing in normal controls and dyspneic patients . This may be affected by gender and body weight when using the reported-algorithm for dyspneic patients AIM To describe changes in chest pain and dyspnoea during a period of 15 years after coronary artery bypass grafting ( CABG ) and to define factors at the time of operation that were associated with the occurrence of these symptoms after 15 years . DESIGN Prospect i ve observational study in western Sweden . SUBJECTS All patients who underwent first-time CABG , without simultaneous valve surgery , between 1 June 1988 and 1 June 1991 . There were no exclusion criteria . FOLLOW-UP All patients were followed up prospect ively for 15 years . The evaluation of symptoms took place through postal question naires prior to and 5 , 10 and 15 years after the operation . RESULTS Totally , 2000 patients were included in the survey and 904 ( 45 % ) of them survived to 15 years . Among these 904 survivors , the percentage of patients with chest pain increased from 44 % to 50 % between the 5- and 15-year follow-up ( p=0.004 ) . The percentage of patients who reported symptoms of dyspnoea increased from 60 % after 5 years to 74 % after 15 years ( p<0.001 ) . Factors at the time of surgery that independently tended to predict chest pain after 15 years were higher age ( p=0.04 ) and prolonged duration of symptoms prior to surgery ( p=0.04 ) . Predictors of dyspnoea after 15 years were higher age ( p<0.0001 ) , the use of inotropic drugs at the time of surgery ( p=0.001 ) , a history of diabetes ( p=0.01 ) and obesity ( p=0.01 ) . CONCLUSION After CABG , relief from chest pain and dyspnoea is generally maintained over a long period of time . Eventually , however , functional-limiting symptoms tend to recur and about half the patients report symptoms of chest pain , while three-quarters report dyspnoea after 15 years . Even if no clear predictor of chest pain was found at the time of surgery , age , the use of inotropic drugs , diabetes and obesity predicted dyspnoea The primary purpose of this study was to determine if there are three distinct factors representing ratings of dyspnea during laboratory exercise , clinical ratings of dyspnea , and pulmonary function in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) ( n = 92 ) using factor analysis . Subjects ( mean age 66 + /- 7 yrs ; FEV1 % predicted 44.7 + /- 14.0 ) were r and omly assigned to one of three treatment groups to test the effects of three education and exercise training programs . Outcomes were evaluated at baseline and at 2 months after the intervention . Dyspnea ratings with laboratory exercise ( SOB ) were measured during incremental ( ITT ) and endurance ( ETT ) treadmill tests , and a six-minute walk ( 6MW ) using the modified Borg scale . Clinical measures of dyspnea were measured with the Baseline and Transitional Dyspnea Index ( BDI/TDI ) , UCSD Shortness of Breath Question naire ( SOBQ ) , Medical Research Council Dyspnea Scale ( MRC ) , Dyspnea subscale of the Chronic Respiratory Question naire ( CRQ-D ) , and a global dyspnea question . Pulmonary function parameters included FEV1 % predicted , FEV1/FVC , and RV/TLC . The factor analysis yielded three factors that accounted for 58.7 % of the total variance in the data : Factor 1 , " Dyspnea with Laboratory Exercise " comprised ETT SOB end , ETT SOB isotime , ITTSOB end , ITT SOB isotime , ITT SOB/Time and ETT SOB/Time . Factor 2 , " Clinical Dyspnea , " comprised 6MW SOB , 6MW SOB/Feet , BDI , SOBQ , MRC , Global SOB , CRQ-D. Measures of airway resistance ( FEV1 % predicted , FEV1/FVC ) and hyperinflation ( RV/TLC ) loaded on a third factor , " Pulmonary Function . " An additional post hoc factor analysis with post-intervention data provided similar results . The Global SOB question and ITT SOB isostage variables were relatively more sensitive to change compared to the other outcome variables . We conclude that pulmonary function , clinical ratings of dyspnea , and laboratory ratings of dyspnea are three separate and independent factors and should be included in the routine clinical evaluation of patients with COPD BACKGROUND B-type natriuretic peptide ( BNP ) is valuable in diagnosing heart failure ( HF ) , but its utility in obese patients is unknown . Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF ; however , there is an inverse relation between BNP levels and body mass index . We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis . METHODS The Breathing Not Properly Multinational Study was a 7-center , prospect i ve study of 1586 patients who presented to the Emergency Department with acute dyspnea . B-type natriuretic peptide was measured on arrival . Height and weight data were available for 1368 participants . The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results . RESULTS Heart failure was the final diagnosis in 46.1 % . Mean BNP levels ( pg/mL ) in lean , overweight/obese , and severely/morbidly obese patients were 643 , 462 , and 247 for patients with acute HF , and 52 , 35 , and 25 in those without HF , respectively ( P < .05 for all comparisons except 35 vs 25 ) . B-type natriuretic peptide cut-points to maintain 90 % sensitivity for a HF diagnosis were 170 pg/mL for lean subjects , 110 pg/mL for overweight/obese subjects , and 54 pg/mL in severely/morbidly obese patients . CONCLUSIONS Body mass index influences the selection of cut-points for BNP in diagnosing acute HF . A lower cut-point ( BNP > or = 54 pg/mL ) should be used in severely obese patients to preserve sensitivity . A higher cut-point in lean patients ( BNP > or = 170 pg/mL ) could be used to increase specificity BACKGROUND The purpose of the study is to describe ( a ) changes in physical activity and symptoms of chest pain and dyspnea during 10 years after coronary artery bypass grafting ( CABG ) and ( b ) risk indicators for chest pain and dyspnea 10 years after CABG . METHODS This is a prospect i ve observational study in Western Sweden . The study includes all patients who underwent CABG without simultaneous valve surgery and with no previous CABG between June 1 , 1988 , and June 1 , 1991 . All patients were prospect ively followed up for 10 years . Evaluation of symptoms took place via postal inquiries before , 5 , and 10 years after the operation . RESULTS In all , 2,000 patients participated in a survey evaluating chest pain and dyspnea during 10 years after CABG . The overall 10-year mortality was 32 % . The proportion of patients with no chest pain increased from 3 % before surgery to 56 % 5 years after the operation and 54 % after 10 years . There was only one predictor for chest pain after 10 years and that was the duration of angina pectoris before surgery . The proportion of patients with no dyspnea increased from 12 % before surgery to 40 % after 5 years but decreased to 31 % after 10 years . The most significant predictors for dyspnea after 10 years were female sex , obesity , diabetes mellitus , high age , duration of angina pectoris , functional class before CABG , and number of days in intensive care unit after CABG . CONCLUSION During 10 years after CABG , one third died . After 10 years , 54 % of the survivors were free from chest pain and 31 % were free from dyspnea . Predictors for chest pain and dyspnea could be defined and reflected age , history , sex , obesity , preoperative complications , and symptom severity The original chronic respiratory question naire ( CRQ ) , one of the most widely used measures of health-related quality of life ( HRQL ) in chronic respiratory disease ( CRD ) , is traditionally interviewer administered ( IA ) and includes an individualised dyspnoea domain . The present authors studied the impact of self-administered ( SA ) and st and ardised dyspnoea questions on CRQ measurement properties . In a factorial design multicentre trial , 177 patients with CRD ( mean age 67.7 yrs ; mean forced expiratory volume in one second per cent predicted 44.6 % ) were r and omised to CRQ-IA ( n = 86 ) or CRQ-SA ( n = 91 ) , and to initially complete the st and ardised or individualised items before and after respiratory rehabilitation . While maintaining validity , the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains . Compared with the st and ardised dyspnoea domain , the individualised dyspnoea domain indicated greater responsiveness . The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA . In conclusion , self-administration and st and ardisation of the chronic respiratory question naire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory question naire . These results challenge the assumption that interviewer-administered question naires are superior to self-administered question naires in older patients with chronic respiratory disease Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials OBJECTIVE The objective of this prespecified sub study of the AFFIRM study , in which no differences in survival or event rates were found in patients with atrial fibrillation ( AF ) r and omized to either rate control or rhythm control , was to test the null hypothesis that quality of life ( QoL ) is equal with rate- versus rhythm-control treatment strategies in AF . METHODS Fifty-six ( 25 % ) of AFFIRM sites were r and omly selected to recruit AFFIRM patients for the QoL sub study . Instruments used in the QoL assessment were ( 1 ) Perceived Health ; ( 2 ) the Cantril Ladder of Life ; ( 3 ) the Short Form 36 survey ; ( 4 ) the QoL Index ; and ( 5 ) the Symptom Checklist : Frequency and Severity . Data were collected at baseline , 2 months , 12 months , and annually ; data are reported through 4 years of follow-up . RESULTS Baseline characteristics of the AFFIRM QoL patients ( n = 716 ) were generally similar to those of the rest of AFFIRM patients . Quality -of-life scores were similar in rate- and rhythm-control assignment groups at all time points . Quality -of-life scores were similar whether the actual rhythm was sinus or AF . Scores increased from baseline to subsequent time points similarly for both groups ; these improvements were not additive over time . CONCLUSIONS Quality of life was comparable between rate- and rhythm-control treatment strategies . In addition , QoL was similar with sinus rhythm versus AF . Attempts to improve QoL by restoring sinus rhythm will usually be unsuccessful A question naire developed by the International Union against Tuberculosis and Lung Disease ( IUATLD ) to assess bronchial symptoms has been tested for its ability to predict the bronchial response to histamine in adults aged 18 - 64 years living in two areas of southern Engl and . A number of questions were found to be independently associated with increased reactivity in the first r and omly selected half of the subjects . These symptoms included wheeze , waking at night with shortness of breath , tightness in the chest or shortness of breath when exposed to animals , dust or feathers and the non-specific symptom of persistent problems with breathing . A predictive score based on these symptoms was more sensitive and only slightly less specific than the question on wheeze alone in predicting the response to histamine in the second half of the subjects . Questions about asthma though more specific were considerably less sensitive than either . Symptoms did not differentiate between reactivity associated with positive skin tests and that associated with smoking BACKGROUND Previous studies of the qualitative sensation of breathlessness have suggested that greater sensory discomfort is reported as airflow obstruction increases . This study investigated relationships between the language of breathlessness and severity of impairment in subjects with COPD . METHODS Using a prospect i ve , observational approach , subjects completed a structured interview in which they volunteered words to describe their sensation of breathlessness and endorsed statements from a preexisting descriptor list . Global impairment was assessed by the BMI , airflow obstruction , dyspnea , and exercise capacity ( BODE ) index . Independent t tests and logistic regression analyses ( odds ratios ) were used to assess relationships between language categories and severity of impairment . RESULTS In this group of 91 people ( 47 men , 70 + /- 10 years of age , percent predicted FEV(1 ) 54 + /- 23 ) , subjects volunteering extreme affective descriptors ( frightening , awful , worried ) had greater impairment ( BODE index , perceived respiratory disability , functional exercise capacity , and airways obstruction ) , and this language category was significantly associated with increasing BODE index scores ( odds ratio [ OR ] = 1.49 ; 95 % CI , 1.18 to 1.86 ; P = .001 ) . Descriptors denoting heavy , rapid , more , shallow , or does not go in or out all the way were significantly less likely to be selected as BODE index scored increased ( OR = 0.75 ; 95 % CI , 0.16 to 0.93 ) . CONCLUSIONS Affective descriptors or the emotional response to the sensation of breathlessness have a significant relationship with severity of COPD impairments . Affective descriptors may reflect the degree of threat imposed by the sensation and predict the likelihood of long-term behavioral changes |
519 | 23,711,416 | The results of the meta- analysis showed a statistically significant difference in efficacy in favour of ketoprofen .
Heterogeneity for the analysed efficacy outcome was not statistically significant in any of the meta-analyses .
The efficacy of orally administered ketoprofen in relieving moderate-severe pain and improving functional status and general condition was significantly better than that of ibuprofen and /or diclofenac | OBJECTIVES The aim of this systematic review of the literature and meta- analysis of r and omised controlled trials ( RCTs ) was to compare the efficacy of orally administered ketoprofen with that of ibuprofen and /or diclofenac . | Purpose : Non-steroidal anti-inflammatory drugs ( NSAIDs ) are used as analgesic in postoperative pain to reduce opioid side effects , such as drowsiness and nausea . However , NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric , renal , and coagulation parameters . This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients . Methods : One hundred and twenty patients scheduled for elective CABG surgery were enrolled in r and omized , double blind , controlled study . St and ardized fast track cardiac anesthesia was used . One dose of drug ( 75 mg diclofenac , 100 mg ketoprofen , 100 mg indomethacin , or placebo ) was givenpr one hour before tracheal extubation and a second dose 12 hr later . Pain was treated with morphineiv and acetaminophenpo . Visual analogue pain scores were recorded at baseline , 3 , 6 , 12 and 24 hr after the first dose of drug . Results : There were no differences among the groups in pain scores . Only patients who received diclofenac required less morphine than patients in the control group ( P<0.05 ) . When the total amounts of pain medications were computed to morphine equivalents , only patients in the diclofenac group received less pain medications than the placebo group ( P<0.05 ) . Proportion of patients with postoperative increase of creatinine level ( 20 % and over ) did not differ between placebo and drug groups . Conclusion : Non-steroidal anti-inflammatory drugs may be used for anaalgesia management post CABG surgery in selected patients . Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively . RésuméObjectif : Les anti-inflammatoires non stéroïdiens ( AINS ) servent d’analgésique postopératoire et réduisent les effets secondaires des opioïdes , comme la somnolence et les nausées . Leur emploi en cardiochirurgie est plutôt restreint où on craint des effets gastriques et rénaux indésirables et des modifications de la coagulation . On a voulu évaluer l’efficacité et la sécurité d’emploi analgésique de trois AINS chez des patients qui subissent un pontage aortocoronarien . Méthode : L’étude r and omisée , contrôlée et à double insu a porté sur 120 patients qui devaient subir un pontage aortocoronarien . Une anesthésie cardiaque normalisée pour un séjour hospitalier écourté a été utilisée . Une dose de médicament ( 75 mg de diclofénac , 100 mg de kétoprofène , 100 mg d’indométhacine , ou un placebo ) a été administréepr une heure avant l’extubation endotrachéale et une seconde dose 12 h plus tard . La douleur a été traitée avec de la morphineiv et de l’acétaminophènepo . Les scores de douleur ont été enregistrés à l’échelle visuelle analogique au début , puis 3 , 6 , 12 et 24 h après la première dose de médicament . Résultats : Les scores de douleur n’ont pas présenté de différence intergroupe . Seuls les patients du groupe diclofénac ont dem and é moins de morphine que ceux du groupe témoin ( P<0,05 ) . Lorsque les quantités totales d’analgésiques ont été calculées en équivalents de morphine , seuls les patients du groupe diclofénac avaient reçu moins d’analgésique que les témoins ( P<0,05 ) . La proportion de patients qui présentaient une augmentation postopératoire du niveau de créatinine ( 20 % et plus ) ne différait pas du groupe placebo aux autres groupes . Conclusion : Les anti-inflammatoires non stéroïdiens sont utiles en analgésique postopératoire chez des patients qui subissent un pontage aortocoronarien planifié . Le diclofénac semble offrir la meilleure analgésie en réduisant les besoins de morphine et d’autres analgésiques Under double-blind , crossover conditions , 43 women with primary dysmenorrhea received ketoprofen , ibuprofen , and placebo during three consecutive menstrual cycles . Pain intensity and pain relief were determined before and for 6 hours after the loading dose ( ketoprofen 150 mg , ibuprofen 800 mg ) and before and 2 hours after the maintenance dose ( ketoprofen 75 mg , ibuprofen 400 mg ) . Mean pain intensity difference and pain relief scores consistently indicated greater pain relief after the loading doses of ketoprofen and ibuprofen than after placebo . Significant ( P less than 0.05 ) mean changes that were measured by 13 indices of analgesia after the loading doses of both ketoprofen and ibuprofen indicated greater efficacy for the active treatments than for placebo . The patients ' global evaluations after the loading doses were significantly ( P less than 0.05 ) better for the active treatments than for placebo . The efficacy results were similar after the maintenance doses . The rates of a " good " to " excellent " response were 77 % for ketoprofen , 73 % for ibuprofen , and 35 % for placebo . Ketoprofen and ibuprofen were equally well tolerated , the most frequent adverse experiences being gastrointestinal symptoms for ketoprofen and central nervous system side effects for ibuprofen A double-blind parallel multi-centre study of 102 patients with rheumatoid arthritis ( RA ) was performed , comparing ibuprofen ( 1200 - 2400 mg daily ) and ketoprofen ( 150 - 300 mg daily ) a new non-steroidal , anti-inflammatory agent , over a three month period . Ketoprofen was well tolerated and shown to have comparable efficacy with ibuprofen . Longterm efficacy and tolerance studies are indicated In a multi-centre double-blind cross-over trial using the double-placebo technique , 55 patients with rheumatoid arthritis were treated for 10 days for each trial drug with ketoprofen ( 200 mg/day ) and ibuprofen ( 1200 mg/day ) . Both drugs induced a clinical ly and statistically significant improvement of all the symptoms studied , except for pain at night during ibuprofen administration . Ketoprofen displayed a therapeutic efficacy significantly superior to ibuprofen in five of the eight symptoms studied . Side-effects were recorded in 10 patients receiving ketoprofen ( one patient withdrew because of heartburn ) and in nine patients receiving ibuprofen Preoperative treatment with controlled-release ketoprofen or diclofenac was compared in 56 out- patients , for control of postoperative dental pain , following unilateral or bilateral surgical removal of lower third molars . Six patients were excluded due to non-compliance , leaving 50 evaluable patients . Patients were assessed by the dental surgeon , on the day of the operation and one week later , prior to removal of sutures . Additionally , patients completed a daily diary during the postoperative week . Following surgery , scores for grade d dental pain , consumption of paracetamol , incidence of dental bleeding , dysphagia , sleep disturbance and trismus were similar for the two treatment groups . However , median pain scores were consistently elevated in the diclofenac group over those seen with the ketoprofen group . The four adverse events reported were all minor and posed no problem to patient management A double-blind cross-over study of ketoprofen ( Orudis ) 150 mg daily and ibuprofen ( Brufen ) 1,200 mg daily was carried out in 35 out patients with rheumatoid arthritis . Results suggest that analgesic and anti-inflammatory activity of ketoprofen is superior to that of ibuprofen . Significantly greater pain relief ( P < 0·05 ) and reduction in joint circumference ( P < 0·01 ) was obtained with ketoprofen than with ibuprofen . Side effects of the drugs were comparable and not serious A comparative controlled study was carried out in 40 patients suffering from rheumatoid arthritis , osteoarthrosis or ankylosing spondylitis to assess the efficacy of ketoprofen and ibuprofen . Patients were allocated at r and om to receive either 100 mg ketoprofen twice daily or 400 mg ibuprofen 3-times daily over a period of 3 months . Subjective overall assessment s of symptoms , based on rating scale scores for pain , duration of morning stiffness and inflammation , showed that there was a greater , more rapid and more sustained improvement in those patients treated with ketoprofen . Measurements of inflamed joint size and of grip strength also improved more with ketoprofen than with ibuprofen . Side-effects , notably nausea , epigastric discomfort and abdominal pain , were more frequent and severe with ketoprofen , leading to the withdrawal of 2 patients in the early stage of the trial , and were probably related to the high dosage used . Three patients receiving ibuprofen needed 7 injections of ACTH to control their symptoms Eighteen patients with rheumatoid arthritis were treated for 3 months with controlled release ketoprofen ( Oruvail ) 100 mgm once daily ( 9 patients ) or diclofenac sodium ( Voltaren ) 25 mgm three times daily ( 9 patients ) . Patients were evaluated at the start of the study and at subsequent visits on days 28 , 56 and 84 . Clinical evaluation included assessment of severity and duration of morning stiffness and the severity of pain and Joint tenderness . Patients were instructed not to take any other nonsteroidal anti -Inflammatory drug , although paracetamol tablets were provided for pain relief if required . Over the study period patients receiving ketoprofen showed a significant reduction in severity of pain , Joint tenderness and morning stiffness . Patients receiving diclofenac sodium showed a significant decrease only In morning stiffness . No estimation of patient compliance or of consumption of paracetamol was made during the study . The incidence of side effects was similar with both drugs , and liver function tests , kidney function , electrolytes and haematology were not affected by drug treatment . Six patients withdrew from the study , three from each drug group . Both ketoprofen and diclofenac sodium were concluded to have beneficial therapeutic effects in patients with rheumatoid arthritis when administered at their minimum recommended dose levels Ninety patients with rheumatoid arthritis completed a double-blind crossover trial comparing fenoprofen , ibuprofen , ketoprofen , and naproxen . Fenoprofen and naproxen were slightly more effective than the other two drugs but there were striking individual variations in response . Groups of patients could be identified who preferred each of the four drugs . The commonest side effects were those related to the upper gastrointestinal tract ; these showed individual variation and seldom occurred with more than one or two of the drugs . Side effects were least common with ibuprofen and naproxen . Since naproxen combined greater effectiveness with a lower incidence of side effects it must be regarded as the first choice among these drugs . It may be necessary to try several drugs before finding the right one for a particular patient |
520 | 25,425,092 | In both categories there were a number of factors might have influenced the results but sensitivity analysis was limited because of the small number of studies and participants .For both acute and chronic painful conditions any evidence of efficacy came from the older , smaller studies , while the larger , more recent studies showed no effect .
The evidence does not support the use of topical rubefacients containing salicylates for acute injuries or chronic conditions .
They seem to be relatively well tolerated in the short-term , based on limited data .
The amount and quality of the available data mean that uncertainty remains about the effects of salicylate-containing rubefacients | BACKGROUND Rubefacients containing salicylates cause irritation of the skin and are believed to relieve various musculoskeletal pains .
They are available on prescription , and are common components in over-the-counter remedies .
This is an up date of a review of rubefacients for acute and chronic pain , originally published in 2009 , which found limited evidence for efficacy .
OBJECTIVES To assess the efficacy and safety of topically applied salicylates in acute and chronic musculoskeletal pain in adults . | OBJECTIVE To assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee . DESIGN R and omised , double-blind , placebo-controlled study . SETTING Rheumatology Clinic of St Vincent 's Hospital , Sydney , New South Wales ( a tertiary referral hospital ) , June 1993 to October 1994 . PATIENTS 116 patients with pain associated with osteoarthritis of the hip and /or knee ( diagnosed by criteria of the European League against Rheumatism ) , drawn from patients attending the Clinic or self-referred after newspaper advertisements . INTERVENTION Copper-salicylate or placebo gel ( 1.5 g ) applied twice daily to the forearm for four weeks . OUTCOME MEASURES Self- assessment of pain before the trial and after two and four weeks of treatment ; patient and investigator assessment s of efficacy ; additional analgesia required ; adverse reactions ; and withdrawal rates . RESULTS Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20 % . There was no significant difference between the two groups for decrease in pain score , patient and investigator efficacy ratings , number of patients requiring paracetamol for extra analgesia ( active , 77 % ; placebo , 71 % ) and average dose of paracetamol ( active , 555 mg/day ; placebo , 600 mg/day ) . Significantly more patients in the copper-salicylate group reported adverse reactions ( 83 % versus 52 % of the placebo group ) , most commonly skin reactions , and withdrew from the trial because of these reactions ( 17 % versus 1.7 % of the placebo group ) . CONCLUSION Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee , but produced significantly more skin rashes Objective : To determine the clinical effects of the treatment of lumbar disc herniation with herbal magnetic corsets . Design : A r and omized control trial . Setting : The outpatient and inpatient departments of the Rehabilitation Center of the West China Hospital . Patients : Sixty patients with clinical ly diagnosed lumbar disc herniation were included in the study . Interventions : Both groups received lumbar traction , medium frequency electrotherapy and massage , whereas the experimental group wore herbal magnetic corsets in addition . Main outcome measures : Pain and lumbar function were assessed before treatment and at one week , two weeks and four weeks after intervention . Results : Both groups reported improvements in pain and lumbar function after treatment ( P 0.05 or P 0.001 ) . However , the experimental group reported gradually increasing relief over time leading to a better curative effect than observed in the control group ( P 0.05 for visual analogue scale or P 0.001 for lumbar function ) . Conclusion : Herbal magnetic corsets can facilitate the reduction of pain caused by lumbar disc herniation and can improve lumbar function . This is a safe and effective non-operative therapeutic option for treatment of lumbar disc herniation Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Enelbin-Rheuma-ointment and a reference ointment were compared with regard to effectiveness in a double-blind trial in 100 patients with gonarthrosis , osteoarthrosis of the spine and humeroscapular periarthropathy . Both ointments showed good results regarding spontaneous pain , pain on pressure and motion , reduction of mobility , swelling and muscular tension . The success of treatment was statistically significantly better in the Enelbin-Rheuma-ointment treated patients Abstract This r and omized , double-blind study was design ed to evaluate the effectiveness of the topical cream Theraflex-TMJ ( NaBob/Rx , San Mateo , CA ) in patients with masseter muscle pain and temporom and ibular joint ( TMJ ) pain . Fifty-two subjects ( 5 males and 47 females ) were instructed to apply a cream over the afflicted masseter muscle(s ) or over the jaw joint(s ) twice daily for two weeks . Theraflex-TMJ cream was used by the experimental group , while a placebo cream was used by the control group . The means of pain ratings were calculated prior to the application of the cream ( baseline ) , after ten days of tx ( period 1 ) , and 15 days of tx ( period 2 ) days of treatment and five days after stopping the treatment ( follow-up ) . There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 ( p<0.01 ) , period 2 ( p<0.001 ) , and follow-up ( p<0.01 ) . For the control group , no significant differences were found between the different time periods ( p>0.05 ) . There was evidence of minor side effects such as skin irritation and /or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups . The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporom and ibular joint BACKGROUND An occlusive patch formulation containing 10 % methyl salicylate and 3 % l-menthol was recently approved by the US Food and Drug Administration for the treatment of mild to moderate pain . Despite widespread use of counterirritants , including methyl salicylate and menthol , for topical pain relief , published efficacy and safety data regarding the use of the agents alone or in combination are limited . OBJECTIVE The goal of this study was to determine the efficacy and safety profile of a patch containing 10 % methyl salicylate and 3 % l-menthol compared with a placebo patch in adult patients with mild to moderate muscle strain . METHODS Eligible patients were men or women aged > or=18 years with a clinical diagnosis of mild to moderate muscle strain . Patients were r and omly assigned to receive either 1 active patch or 1 placebo patch applied to the skin at the affected area ( ie , shoulder , upper back , upper arm , neck , calf , thigh , forearm , abdomen ) . Pain intensity was assessed on a 100-mm visual analog scale while at rest and with movement for 12 hours after patch application . The primary efficacy end point was the summed pain intensity difference score through 8 hours ( SPID8 ) with movement . Analyses included use of descriptive statistics and an ANOVA model . Safety data , including adverse events , and secondary efficacy end points were also evaluated . RESULTS A total of 208 patients ( 104 men , 104 women ; age range , 18 - 78 years ) were r and omized to 1 of 2 study groups ( 105 in the active-patch group [ mean age , 37.3 years ] , 103 in the placebo-patch group [ mean age , 38.1 years ] ) . The primary efficacy analysis ( SPID8 with movement ) indicated that patients receiving the active patch experienced significantly greater pain relief ( approximately 40 % ) than those patients receiving a placebo patch ( mean [ SD ] , 182.6 [ 131.2 ] vs 130.1 [ 144.1 ] ; P = 0.005 ) . Analysis of the per- protocol population also found significantly more relief ( P = 0.024 ) in the active-patch group ( 176.2 [ 131.4 ] ; n = 92 ) versus the placebo-patch group ( 130.2 [ 144.0 ] ; n = 96 ) . Statistical analysis of secondary efficacy measures supported the primary end-point results . The number of patients experiencing any type of adverse event was comparable between study groups ( active patch , 6.7 % [ 7 events ] ; placebo patch , 5.8 % [ 6 events ] ) . No serious adverse events were reported during the study . CONCLUSION A single , 8-hour application of a patch containing methyl salicylate and l-menthol provided significant relief of pain associated with mild to moderate muscle strain in these adult patients compared with patients receiving a placebo patch Twenty-five patients with symptomatic osteoarthritis ( OA ) of the knee were treated topically for one week with either 10 % trolamine salicylate cream or placebo cream in a r and omized double-blind crossover study . No significant difference was found in subjective or objective measures of pain relief between the treatment and control groups . Eight patients preferred " active " test cream , six preferred placebo , and 11 had no preference . No side effects were reported . Topically applied 10 % trolamine salicylate cream did not relieve the pain of OA of the knee any more than did placebo Forty patients with acute mechanical low-back pain were treated in a double-blind manner with either Rado-Salil ® or placebo for 14 days . Statistically significant improvements in spontaneous pain , muscular contracture and in both the patient 's and physician 's opinions occurred by day 3 . These improvements persisted at day 14 and , in addition , there were statistically significant improvements in the finger – floor distance and the degree of lumbar extension . Treatment with Rado-Salil ® also allowed significant reduction in the use of oral analgesics . Only a few localized transient side-effects , requiring no specific treatment , were observed In a r and omised , placebo-controlled , double-blind study with parallel group comparison , the efficacy and tolerability of topical treatment with a mucopolysaccharide polysulphate/salicylic acid cream was investigated in 156 patients with acute sprains of the knee or ankle joint . There was a more rapid reduction in pain on movement ( the main parameter ) in the active drug group compared with the placebo group . On day 9 after r and omisation the difference was highly significant . There were no adverse events in the active drug group & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Acute low back pain is a very common condition in Western industrialised countries . In most cases analgesics or topical medications are prescribed at first encounter with the general practitioner ( GP ) . The aim of this study was to investigate whether the homeopathic gel Spiroflor SRL gel ( SRL ) is equally effective and better tolerated than Cremor Capsici Compositus FNA ( CCC ) in patients with acute low back pain . A multi-centre , r and omised , double-blind , controlled clinical trial was conducted in the practice s of 19 GPs in the districts of Bristol and Manchester , UK . One hundred and sixty-one subjects suffering from acute low back pain were treated for one week either with SRL or with CCC . Pain was scored on a 100 mm visual analogue scale ( VAS ) . Main efficacy parameter VAS reduction was compared between treatments . Evaluation of safety was primarily based on the number of subjects with adverse events ( AEs ) , withdrawals due to an AE and adverse drug reactions ( ADRs ) . The mean difference between the VAS reduction in the SRL group and the CCC group adjusted for VAS at baseline and age was -0.6 mm ( 90 % CI = -6.5 - 5.3 mm ) . Fewer subjects in the SRL group ( 11 % ) experienced an AE than in the CCC group ( 26 % ) . The same applies to the number of subjects with an ADR ( 3/81 = 4 % vs 18/74 = 24 % ) and the number of subjects withdrawn due to an ADR ( 0/81 = 0 % vs 8/74 = 11 % ) . In conclusion , SRL and CCC are equally effective in the treatment of acute low back pain , however , SRL has a better safety profile . Spiroflor SRL gel is preferable to Capsicum-based products for the topical treatment of low back pain , because of the lower risk of adverse effects 2-(2-Hydroxyethoxy)ethyl-N-(a , a , a-trifluoro-m-tolyl)anthranilate ( etofenamate , Rheumon Gel ) , a percutaneously active antirheumatic containing etofenamate as active principle has been subjected to clinical studies in both hospitalized and out- patients in various types of rheumatic disease . These trials included double-blind studies against placebo gel , controlled comparative studies against two topical commercial products ( ointmentI : combination of 2-hydroxyethyl salicylate and p-menthan-3-ol ; ointment II : 3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine ) and open trials for efficacy and tolerance . Of the 760 patients taking part in the trials , 556 were treated with Rheumon Gel Knee osteoarthritis is the most common cause of disability among people and it is a common disease of joints that can lead to cartilage damage . In this study the analgesic effects of a herbal ointment containing cinnamon , ginger , mastic ( Saghez ) and sesame oil is compared with Salicylate ointment in patients suffering from knee osteoarthritis . It was a double-blind r and omized controlled trail study . Patients with diagnosed arthritis were involved in the study and they were divided in two groups via block r and omization method . For six weeks , twice a day , intervention group applied herbal ointment and control group used Salicylate ointment . The severity of pain , morning stiffness and limited motion were measured using Visual Analog Pain Scale . In order to analyze the trends of these three indexes , repeated measurement test was used . Ninety two participates with the mean age of 52.2 ( + /- 12.4 ) years and with the mean disease period of 30.45 ( + /- 30.3 ) months were involved in the study . There was no significant difference between two groups regarding the distribution of sex , weight , height , BMI and the duration of illness . No statistical difference was observed between two groups regarding pain relief , morning stiffness and limited motion ; nevertheless in repeated measurements during second , forth and sixth weeks in both groups the decreasing trend of these three indexes had been statistically significant ( p < 0.0001 ) . It seems that using this herbal combination is clinical ly effective for patients suffering from knee osteoarthritis in order to decrease their pain , morning stiffness and limited motion ; its effect is comparable with Salicylate ointment The efficacy of Mobilat ointment ( 100 g contain : Extract . suprarenale 1.0 g , Mucopolysaccharide-polysulfate 0.2 g , salicylic acid 2.0 g ) in the treatment of acute lateral distortions of the ankle was tested in a r and omised , placebo-controlled , double blind study . The criteria used for the assessment of the progress of healing were the pressure distribution during walking , the swelling of the injured region and the evaluation of pain using a visual analogue scale . During the period of treatment and observation lasting 2 weeks , all the assessment criteria showed a more rapid regression in the symptoms and signs of the disorder on treatment with the active product . The differences were statistically significant for all the criteria assessed Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel . A double blind , multicenter trial , involving 113 patients with nonarticular rheumatic back pain , revealed statistically significant relief of pain as compared with placebo . Local and systemic tolerance was excellent . An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 + /- 0.5 microgram/ml in the synovial fluid and 0.40 + /- 0.23 microgram/ml in the synovial membrane , compared with 0.14 + /- 0.04 microgram/ml in the serum . Genetisinic acid was not detected , while OH-hippuric acid was detected only in the serum and synovial fluid |
521 | 28,884,473 | AUTHORS ' CONCLUSIONS We did not identify widespread differential treatment effects of pharmacotherapy based on genotype .
Some genotype groups within certain ethnic groups may benefit more from NRT or may benefit less from the combination of bupropion with NRT .
Although we found evidence of superior NRT efficacy for NMR slow versus normal metabolisers , because of the lack of heterogeneity between NMR groups , we can not conclude that NRT is more effective for slow metabolisers . | BACKGROUND Smoking cessation therapies are not effective for all smokers , and research ers are interested in identifying those subgroups of individuals ( e.g. based on genotype ) who respond best to specific treatments .
OBJECTIVES To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo .
To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms . | Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts . We report data that vali date a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances . In a cessation study , v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66 . About 43 % vs 13 % quit in the upper vs lower genotype score terciles . Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use . Higher v1.0 scores were associated with ( a ) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence ( P=0.0004 ) and ( b ) lower probabilities of membership in a class that reported escalating use ( P=0.001 ) . These results indicate that : ( a ) we have identified genetic predictors of smoking cessation success , ( b ) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and ( c ) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts Purpose : A new generation of molecularly targeted agents is entering the definitive stage of clinical evaluation . Many of these drugs benefit only a subset of treated patients and may be overlooked by the traditional , broad- eligibility approach to r and omized clinical trials . Thus , there is a need for development of novel statistical methodology for rapid evaluation of these agents . Experimental Design : We propose a new adaptive design for r and omized clinical trials of targeted agents in setting s where an assay or signature that identifies sensitive patients is not available at the outset of the study . The design combines prospect i ve development of a gene expression – based classifier to select sensitive patients with a properly powered test for overall effect . Results : Performance of the adaptive design , relative to the more traditional design , is evaluated in a simulation study . It is shown that when the proportion of patients sensitive to the new drug is low , the adaptive design substantially reduces the chance of false rejection of effective new treatments . When the new treatment is broadly effective , the adaptive design has power to detect the overall effect similar to the traditional design . Formulas are provided to determine the situations in which the new design is advantageous . Conclusion : Development of a gene expression – based classifier to identify the subset of sensitive patients can be prospect ively incorporated into a r and omized phase III design without compromising the ability to detect an overall effect The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy , we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins , namely ARRB2 and HINT1 . Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label r and omized trial . In a logistic regression model controlling for OPRM1 genotype , treatment type , and other covariates , we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up . Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up , but this may not be a pharmacogenetic effect , given that the participants were drug free during this time . Haplotype analysis did not reveal any significant associations for either gene . We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance ; however , interpretation of this finding is limited by the small number of participants with the minor alleles for both genes . Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation , further exploration of opioid pathway genes in larger prospect i ve pharmacogenetic trials may be warranted Stopping smoking is difficult even with treatment . Many patients prescribed pharmacologic treatments for smoking cessation experience side effects or lack of efficacy . We performed a pharmacogenetic study of the efficacy and tolerability of bupropion and transdermal nicotine ( TN ) , two treatments for smoking cessation . Sample s were drawn from two studies . In the first study ( Maintenance 1 , MT1 ) , 301 smokers received bupropion plus TN for 11 weeks , followed by 14 weeks of placebo or bupropion . In the second study ( MT2 ) , 276 smokers received bupropion and TN for 8 weeks . We focused on eight SNPs in the 15q24 region , which contains the genes for the nicotinic cholinergic receptor subunits CHRNA5 , CHRNA3 , and CHRNB4 , and has previously been implicated in nicotine addiction and smoking cessation . Analyses of baseline smoking quantity ( SQ ) identified an association between SQ and both the functional CHRNA5 SNP rs16969968 ( D398N ) and the CHRNA3 SNP rs1051730 ( Y215Y ) in a combined cohort containing MT1 and MT2 . An association between SQ and ethnicity was also identified in the combined cohort . Pharmacogenetic analysis showed a significant association between rs8192475 ( R37H ) in CHRNA3 and both higher craving after quitting and increased withdrawal symptoms over time in MT2 . Two markers for point prevalence abstinence , CHRNA5 SNP rs680244 and CHRNB4 SNP rs12914008 , were also identified in MT2 , with the strongest findings at week 52 . These results provide further support for the role of the CHRNA5/A3/B4 subunits in determining number of cigarettes smoked and response to smoking cessation therapy . © 2011 Wiley‐Liss , We conducted gender-stratified analyses on a systems-based c and i date gene study of 53 regions involved in nicotinic response and the brain — reward pathway in two r and omized clinical trials of smoking cessation treatments ( placebo , bupropion , transdermal and nasal spray nicotine replacement therapy ) . We adjusted P-values for multiple correlated tests , and used a Bonferroni-corrected α-level of 5 × 10−4 to determine system-wide significance . Four single-nucleotide polymorphisms ( rs12021667 , rs12027267 , rs6702335 , rs12039988 ; r2>0.98 ) in erythrocyte membrane protein b and 4.1 ( EPB41 ) had a significant male-specific marginal association with smoking abstinence ( odds ratio (OR)=0.5 ; 95 % confidence interval ( CI ) : 0.3–0.6 ) at end of treatment ( adjusted P<6 × 10−5 ) . rs806365 in cannabinoid receptor 1 ( CNR1 ) had a significant male-specific gene – treatment interaction at 6-month follow-up ( adjusted P=3.9 × 10−5 ) ; within males using nasal spray , rs806365 was associated with a decrease in odds of abstinence ( OR=0.04 ; 95 % CI : 0.01–0.2 ) . While the role of CNR1 in substance abuse has been well studied , we report EPB41 for the first time in the nicotine literature Purpose : Many anticancer therapies benefit only a subset of treated patients and may be overlooked by the traditional broad eligibility approach to design phase III clinical trials . New biotechnologies such as microarrays can be used to identify the patients that are most likely to benefit from anticancer therapies . However , due to the high-dimensional nature of the genomic data , developing a reliable classifier by the time the definitive phase III trail is design ed may not be feasible . Experimental Design : Previously , Freidlin and Simon ( Clinical Cancer Research , 2005 ) introduced the adaptive signature design that combines a prospect i ve development of a sensitive patient classifier and a properly powered test for overall effect in a single pivotal trial . In this article , we propose a cross-validation extension of the adaptive signature design that optimizes the efficiency of both the classifier development and the validation components of the design . Results : The new design is evaluated through simulations and is applied to data from a r and omized breast cancer trial . Conclusion : The cross-validation approach is shown to considerably improve the performance of the adaptive signature design . We also describe approaches to the estimation of the treatment effect for the identified sensitive sub population . Clin Cancer Res ; 16(2 ) ; INTRODUCTION We evaluated chr6q25.3 organic cation transporter gene ( SLC22A1 , SLC22A2 , SLC22A3 ) variation and response to smoking cessation therapies . The corresponding proteins are low-affinity transporters of choline , acetylcholine and monoamines , and smoking cessation pharmacotherapies expressed in multiple tissues . METHODS We selected 7 common polymorphisms for mega-regression analysis . We assessed additive model association of polymorphisms with 7-day point prevalence abstinence overall and by assigned pharmacotherapy at end of treatment and at 6 months among European-ancestry participants of 7 r and omized controlled trials adjusted for demographic , population genetic , and trial covariates . RESULTS Initial results were obtained in 6 trials with 1,839 participants . Nominally statistically significant associations of 2 SLC22A2 polymorphisms were observed : ( 1 ) with rs316019 at 6 months , overall ( [ c.808T > G ; p . Ser270Ala ] , OR = 1.306 , 95 % CI = 1.034 - 1.649 , p = .025 ) , and among those r and omized to nicotine replacement therapy ( NRT ) ( OR = 1.784 , 95 % CI = 1.072 - 2.970 , p = .026 ) ; and ( 2 ) with rs316006 ( c.1502 - 529A > T ) among those r and omized to varenicline ( OR = 1.420 , 95 % CI = 1.038 - 1.944 , p = .028 , OR = 1.362 , 95 % CI = 1.001 - 1.853 , p = .04 ) at end of treatment and 6 months . Individuals r and omized to NRT from a seventh trial were genotyped for rs316019 ; rs316019 was associated with a nominally statistically significant effect on abstinence overall at 6 months among 2,233 participants ( OR = 1.249 , 95 % CI = 1.007 - 1.550 , p = .043 ) . CONCLUSIONS The functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with abstinence among European-ancestry treatment-seeking smokers after adjustments for pharmacotherapy , demographics , population genetics , and without adjustment for multiple testing of 7 SNPs . Replication of these preliminary findings in additional r and omized controlled trials of smoking cessation therapies and from multiple continental population s would describe another pharmacogenetic role for SLC22A2/OCT2 INTRODUCTION The α4β2 nicotinic receptor is of central importance in tobacco dependence , while the homomeric α7 receptor may also play a role . In this c and i date gene study , we examine the association between 8 single nucleotide polymorphisms ( SNPs ) in genes coding for nicotinic acetylcholine receptor subunits α4 ( rs1044396 , rs2273504 , rs2236196 , and rs2273502 ) , α7 ( rs2133965 and rs4779969 ) , and β2 ( rs2072660 and rs2072661 ) and smoking abstinence in a cohort of quitters enrolled in a clinical trial of behavioral support . METHODS Data were obtained from the " Patch in Practice " study , involving 925 smokers in the United Kingdom . All participants were given an 8-week course of 15 mg of transdermal nicotine replacement therapy and blood was taken for genotyping . RESULTS Logistic regression analyses assessed the association between each selected SNP and smoking abstinence at 4 , 12 , 26 , and 52 weeks . There were no statistically significant associations with smoking cessation success or nicotine intake assessed by plasma cotinine levels . However , rs2273502 was associated with a consistent ( though nonsignificant ) increase in the odds of abstinence . CONCLUSIONS There was no compelling evidence that these SNPs were associated with a reduced or higher chance of abstinence . However , rs2273502 may be worth investigating in future studies Quitting smoking benefits older individuals , yet few recent studies have described older smokers . The goal of this paper was to test a series of hypotheses about differences between smokers aged 50 years or older ( 50 + ) and those younger than age 50 ( < 50 ) presenting to the same treatment facility during 2002 - 2004 for participation in two r and omized clinical trials : one exclusively for smokers aged 50 + , and a second open to smokers aged 18 or older . As predicted , smokers aged 50 + were more tobacco dependent , had better psychological functioning , and had poorer physical functioning than those aged < 50 . Contrary to predictions , we found no differences in motivation to quit cigarette smoking or in alcohol use . Women aged 50 + were less likely to report marijuana use than women aged < 50 , and less likely than men to receive a positive diagnosis for alcohol abuse . Despite higher scores on measures of tobacco dependence , older smokers were less likely to be diagnosed as tobacco dependent or as having tobacco withdrawal using DSM-IV criteria . Rates of DSM-IV alcohol abuse and dependence were high in both age groups but were higher for smokers aged < 50 . We found no striking differences between studies in reasons for exclusion , but in both the proportion of individuals excluded due to current antidepressant use was high . Implication s for the assessment and treatment of older adults are discussed INTRODUCTION We previously reported evidence that the T allele of the dopamine type-2 receptor ( DRD2 ) rs1800497 polymorphism is associated with improved response to nicotine replacement therapy ( NRT ) relative to placebo and that this association may only be present in females . However , evidence of the poor replication validity of genetic association studies is growing , particularly among those that report subgroup analyses . We therefore attempted to replicate our previous finding of an association between the DRD2 rs1800497 genotype and response to NRT in a new , larger cohort , with greater statistical power . METHODS Participants were r and omly assigned to one of two levels of smoking cessation behavioral support ( usual care vs. weekly support ) . All participants received 8 weeks of 15-mg NRT transdermal patch . RESULTS The presence of one or more T alleles was associated with a slightly but not significantly lower likelihood of abstinence at 3 and 6 months . We found evidence of a genotype x sex interaction effect . However , stratified analyses indicated a main effect of genotype opposite to the effect reported previously , with females carrying one or more copies of the T allele less likely to be abstinent . DISCUSSION Our results do not support an association between the DRD2 rs1800497 ( Taq1A ) polymorphism and response to NRT , contrary to our previous study This study is a r and omized , double-blind , placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment ( CBTD ) and of bupropion , both singularly and in combination , on smoking cessation in adult smokers . As an extension of our previous work , we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors . Participants were 524 smokers ( 47.5 % female , M ( age ) = 44.27 years ) who were r and omized to one of four 12-week treatments : ( a ) st and ard , cognitive-behavioral smoking cessation treatment ( ST ) plus bupropion ( BUP ) , ( b ) ST plus placebo ( PLAC ) , ( c ) st and ard cessation treatment combined with cognitive-behavioral treatment for depression ( CBTD ) plus BUP , and ( d ) CBTD plus PLAC . Follow-up assessment s were conducted 2 , 6 , and 12 months after treatment , and self-reported abstinence was verified biochemically . Consistent with previous studies , bupropion , in comparison with placebo , result ed in better smoking outcomes in both intensive group treatments . Adding CBTD to st and ard intensive group treatment did not result in improved smoking cessation outcomes . In addition , neither CBTD nor bupropion , either alone or in combination , was differentially effective for smokers with single-past-episode major depressive disorder ( MDD ) , recurrent MDD , or elevated depressive symptoms . However , findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample . An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials INTRODUCTION DRD4 Exon III Variable Number of T and em Repeat ( VNTR ) variation was found to interact with bupropion to influence prospect i ve smoking abstinence , in a recently published longitudinal analyses of N = 331 individuals from a r and omized double-blind placebo-controlled trial of bupropion and intensive cognitive-behavioral mood management therapy . METHODS We used univariate , multivariate , and longitudinal logistic regression to evaluate gene , treatment , time , and interaction effects on point prevalence and continuous abstinence at end of treatment , 6 months , and 12 months , respectively , in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial r and omizing participants to active or placebo bupropion . Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy , with a target quit date 2 weeks after initiating both therapies . VNTR genotypes were coded with the long allele dominant result ing in 4 analysis categories . Covariates included demographics , dependence measures , depressive symptoms , and genetic ancestry . We also performed genotype-stratified secondary analyses . RESULTS We observed significant effects of time in longitudinal analyses of both abstinence outcomes , of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes , and of covariates in some analyses . We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele , in the directions previously reported . CONCLUSIONS VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample . Analyses of multiple r and omized clinical trials will enable identification and validation of factors mediating treatment response INTRODUCTION There is increasing evidence that response to pharmacological treatment for nicotine dependence may be moderated by genetic polymorphisms . However , the feasibility , acceptability , and impact of genetically tailoring treatment in real-world clinical setting s are unknown . METHODS We conducted a multiphased , mixed- methods feasibility study with current smokers to develop and evaluate a patient-centered , theoretically grounded personalized medicine treatment protocol . The initial research phase included formative work to develop intervention material s. The second phase included a r and omized pilot trial to evaluate the intervention . Trial participants ( n = 36 ) were genotyped for ANKK1 rs1800497 and were r and omized to receive genetic feedback ( GF ) plus st and ard behavioral counseling ( BC ) for smoking cessation or BC without GF . All participants received genetically tailored pharmacotherapy ( nicotine patch or bupropion ) . RESULTS The intervention was feasible to implement and was acceptable to participants based on satisfaction ratings and objective measures of participation . There was no evidence that the GF result ed in adverse psychological outcomes ( e.g. , depression , fatalism , reduced perceived control over quitting , differential motivation for quitting ) based on quantitative or qualitative outcomes . CONCLUSIONS Study results suggest that it is feasible to offer treatment within a health care setting that includes genetically tailored pharmacotherapy and doing so had no apparent adverse psychological impacts . Further evaluation of pharmacogenetically tailored smoking cessation interventions appears warranted AIMS This study evaluates the relationship of six polymorphisms found in the CHRNA3 , DRD2 and COMT genes with nicotine dependence , the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients . MATERIAL S & METHODS The study included 233 participants from a double-blind , placebo-controlled trial of nicotine patch substitution with a 6-month follow-up period . Nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence ( FTND ) question naire , withdrawal symptoms by the Minnesota Nicotine Withdrawal Scale question naire and smoking cessation by self-reported abstinence at 1 week , 1 month and 6 months after treatment . RESULTS After correcting for multiple testing , three polymorphisms in the DRD2 gene ( Taq1A , Taq1B and Pro319Pro ) were significantly associated with nicotine dependence ( p = 0.018 , p = 0.048 and p = 0.006 , respectively ) . Using a cutoff point for the FTND score , the CHRNA3 Tyr215Tyr ( rs1051730 ) polymorphism was also associated with nicotine dependence ( p = 0.037 and p = 0.074 after correction for multiple testing ) . No association of any of the studied polymorphisms was observed with either smoking cessation or the occurrence of withdrawal symptoms . CONCLUSION This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index ( BMI ) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy ( NRT ) patch or placebo in a r and omized controlled trial , and were followed-up over an 8-year period following their initial cessation attempt . We also investigated possible sex differences in these relationships , given evidence for sex differences in smoking cessation and central opioid mechanisms , as well as some evidence for sex differences in response to NRT . Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment , with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch . Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt , with ex-smokers demonstrating an increase in BMI , and this increase being greater in female subjects than in male subjects . We did not observe any association of OPRM1 genotype with change in BMI , although there was a trend for genotype to influence the observed sex difference in change in BMI over time . Future studies should attempt to replicate these findings , and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes . Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption This r and omized , double-blinded , placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation . Smokers of European ancestry ( N = 291 ) , who were r and omized to receive bupropion or placebo ( 12 weeks ) plus counseling , were genotyped for the dopamine D2 receptor ( DRD2-Taq1A ) , dopamine transporter ( SLC6A3 3 ' VNTR ) , and cytochrome P450 2B6 ( CYP2B6 1459 CT ) polymorphisms . Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2- , 6- , and 12-month follow-ups post quit date . Using generalized estimating equations , we found that bupropion , compared with placebo , was associated with significantly greater odds of abstinence at all time points ( all p values<.01 ) . We found a significant DRD2 x bupropion interaction ( B = 1.49 , SE = 0.59 , p = .012 ) [ corrected ] and a three-way DRD2 x bupropion x craving interaction on 6-month smoking cessation outcomes ( B = -0.45 , SE = 0.22 , p = .038 ) , such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion . Furthermore , there was a significant DRD2 x CYP2B6 interaction ( B = 1.43 , SE = 0.56 , p = .01 ) , such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype . Because the sample size of this study was modest for pharmacogenetic investigations , the results should be interpreted with caution . Although these results require replication , the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and , further , that exploration of gene x gene and gene x craving interactions in future , larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion BACKGROUND Previous research demonstrated the efficacy of sustained release bupropion ( bupropion SR ) for smoking cessation in whites as well as moderate to heavy ( ≥10 cigarettes per day [ CPD ] ) African American smokers . We evaluated whether bupropion SR was effective for smoking cessation among African American light smokers ( ≤10 CPD ) . METHODS A r and omized , double-blind placebo-controlled trial was conducted from December 27 , 2007 , to May 13 , 2010 . All participants were African American light smokers ( ≤10 CPD ) , aged 18 years or older . Participants were r and omly assigned to receive 300 mg bupropion SR ( 150 mg once daily for 3 days and then 150 mg twice daily ) ( n = 270 participants ) or placebo ( n = 270 participants ) for 7 weeks , and up to six sessions of health education counseling . Serum cotinine was measured at baseline ( week 0 ) . The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26 ; a cut point of 15 ng/mL differentiated smokers from nonsmokers . Salivary cotinine-verified smoking abstinence at end of medication treatment at week 7 was also examined . Odds ratios ( OR ) for smoking abstinence and 95 % confidence intervals ( CIs ) were calculated using logistic regression models . All statistical tests were two-sided . RESULTS Participants at baseline visit ( week 0 ) smoked an average of 8.0 CPD and had a mean serum cotinine level of 275.8 ng/mL ( SD = 155.8 ng/mL ) ; most used menthol cigarettes ( 83.7 % ) and smoked within 30 minutes of waking ( 72.2 % ) . After imputing those lost to follow-up as smokers , no statistically significant difference in long-term smoking abstinence rates at week 26 was observed between bupropion SR and placebo groups ( 13.3 % vs 10.0 % , OR = 1.39 , 95 % CI = 0.82 to 2.35 , P = .23 ) . Cotinine-verified smoking abstinence rate at end of medication week 7 was higher in the bupropion SR vs placebo group ( 23.7 % vs 9.6 % , OR = 2.92 , 95 % CI = 1.78 to 4.77 , P < .001 ) . CONCLUSIONS Bupropion SR was effective in promoting smoking cessation during the medication phase of treatment but showed no effect on long-term smoking cessation among African American light smokers . More research is needed to identify strategies for sustaining abstinence among African American light smokers BACKGROUND The selective nicotinic acetylcholine receptor partial agonist , varenicline tartrate , represents a novel type of therapy for smoking cessation . This study evaluated the efficacy , safety , and tolerability of 4 varenicline dose regimens , 2 with progressive dosing over the first week ( eg , titrated ) and 2 with a fixed dosing schedule ( eg , non-titrated ) , for promoting smoking cessation . METHODS This multicenter , double-blind , placebo-controlled study r and omized healthy smokers ( aged 18 - 65 years ) to varenicline tartrate , 0.5 mg twice daily nontitrated ( n = 129 ) , 0.5 mg twice daily titrated ( n = 130 ) , 1.0 mg twice daily nontitrated ( n = 129 ) , 1.0 mg twice daily titrated ( n = 130 ) , or placebo ( n = 129 ) for 12 weeks to aid in smoking cessation . A 40-week follow-up period assessed long-term efficacy . The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52 . RESULTS Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group ( 49.4 % ) and the 0.5-mg group ( 44.0 % ) vs placebo ( 11.6 % ; P<.001 vs both doses ) . Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group ( 22.4 % ; P<.001 ) and the 0.5-mg group ( 18.5 % ; P<.001 ) vs placebo ( 3.9 % ) . Varenicline was generally well tolerated , with nausea occurring in 16 % to 42 % of varenicline-treated subjects . Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation . CONCLUSION Varenicline tartrate , 0.5 mg and 1.0 mg twice daily , is efficacious for smoking cessation The A1 allele of the dopamine D2 receptor gene ( DRD2 ) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior . In a study of smokers enrolled in an open-label , r and omized effectiveness trial , we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling . Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months , respectively , following a target quit date . Compared to women who carry both A2 alleles , women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects ( odds ratio (OR)=1.91 , 95 % confidence interval (CI)=1.01–3.60 ; P<0.04 ) and at 12 months were somewhat more likely to report smoking ( OR=0.76 , 95 % CI=0.56–1.03 ; P<0.076 ) . Significant associations or trends were not observed in men . In women , individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function OBJECTIVE --To assess the effectiveness of 12 weeks ' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking ; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet . DESIGN --Double blind placebo controlled r and omised trial with a 2 x 2 factorial design . SETTING --19 general practice s in Oxfordshire . SUBJECTS--1686 heavy smokers aged 25 - 64 ( mean cigarette consumption 24/day ; mean duration of smoking 25 years ) . MAIN OUTCOME MEASURE -- Sustained cessation for the last four weeks of the 12 week treatment period , confirmed by saliva cotinine estimation ( 226/262 cases ; 86.3 % ) or expired carbon monoxide concentration ( 36/262 ; 13.7 % ) . Patients lost to follow up ( 155/1686 ; 9 % ) were assumed to have continued to smoke . RESULTS --Cessation was confirmed in 163 patients ( 19.4 % ) using the nicotine patch and 99 patients ( 11.7 % ) using the placebo patch ( difference 7.6 % ( 95 % confidence interval 4.2 % to 11.1 % ) ; p < 0.0001 ) . There was no significant advantage in using the more detailed written support material . The most important adverse effect of the patch was local skin irritation , which occurred in 15.8 % ( 133/842 ) and 5.1 % ( 43/844 ) of patients using the nicotine and placebo patches respectively , was grade d as severe in 4.8 % ( 40 ) and 1.1 % ( nine ) , and was stated as a reason for withdrawal from the trial in 9.5 % ( 80 ) and 2.8 % ( 24 ) . CONCLUSION --Nicotine patches are effective in a general practice setting with nursing support , but the extent to which this effect is sustained can not be assessed until the results of longer term follow up are known Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a r and omized , placebo-controlled clinical trial among adult daily smokers . Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated , relative to a placebo medication and assessment control condition . Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment , relative to the placebo medication conditions , for both biochemically confirmed 7-day point-prevalence abstinence ( OR = 1.97 , 95 % CI 1.04 - 3.72 ) and self-reported prolonged abstinence ( OR = 2.90 , 95 % CI 1.66 - 5.06 ) . Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses . Medication effects were more modest for both 12-month point-prevalence abstinence ( OR = 1.47 , 95 % CI 0.74 - 2.92 ) and prolonged abstinence ( OR = 1.34 , 95 % CI 0.66 - 2.72 ) . Counseling was not associated with increases in the likelihood of abstinence at any time point ( odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample ) . Counseling and medication did not significantly interact at any time point , and adding counseling did not improve end-of-treatment point-prevalence abstinence ( OR = 1.17 , 95 % CI 0.68 - 2.03 ) or prolonged abstinence ( OR = 1.26 , 95 % CI 0.75 - 2.12 ) substantially when offered in conjunction with active medication We investigated the association of catechol O-methyltransferase ( COMT ) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt . In addition , we examined the possible moderating influence of sex on any association . The genotype × treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group ( 33 % versus 12 % ) , in comparison to the Met/Val + Val/Val group ( 22 % versus 16 % ) . Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo , with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype . Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies , but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1065–9 Introduction Rates of smoking in the US population have decreased overall , but rates in some groups , including alcoholic smokers , remain high . Many newly sober alcoholics are concerned about their smoking and some attempt to quit . However , quit rates in this population are low . Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment . Methods In this exploratory study , we had two specific aims : ( 1 ) to investigate associations between genetic risk and outcome ; ( 2 ) to investigate whether genetic risk moderates the efficacy of a medication intervention . Data are from a sub sample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence . Subjects were r and omly assigned to bupropion or placebo . All subjects received counseling and nicotine patches . To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile ( ie , a pharmacogenetic approach ) , an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies . Results Although medication efficacy was not moderated by the aggregate genetic risk score , there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment ( 10 weeks ) . Conclusions Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke . Additionally , these findings suggest a strategy for underst and ing and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment ABSTRACT To determine whether the functional mu-opioid receptor ( OPRM1 ) Asn40Asp variant predicts the comparative efficacy of different forms of NRT , we conducted a clinical trial of transdermal nicotine ( TN ) vs nicotine nasal spray ( NS ) in 320 smokers of European ancestry . Smokers carrying the OPRM1 Asp40 variant ( n=82 ) were significantly more likely than those homozygous for the Asn40 variant ( n=238 ) to be abstinent at the end of treatment , and reported less mood disturbance and weight gain . The genotype effect on treatment outcome was most pronounced among smokers receiving TN , particularly during the 21 mg dose phase . Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21 mg dose This study evaluated the relationship between smoking cessation treatment outcome and the DRD2 polymorphism . Participants were 134 smokers who took part in a larger clinical trial evaluating the effects of an antidepressant medication ( venlafaxine or placebo ) plus st and ard care ( brief counseling and nicotine replacement therapy ) . Venlafaxine is an antidepressant that inhibits the reuptake of serotonin and norepinephrine . A1 smokers were expected to quit significantly less often on placebo , although the abstinence rates between A1s and A2s on active drug were not expected to differ ( i.e. , an interaction between genotype and drug was hypothesized ) . In addition , antidepressant therapy was expected to have a similar genotype x treatment interaction on negative affect reduction . The results showed that smokers carrying the DRD2 A1 allele ( A1/A1/A2 ) quit significantly less often than the homozygous A2s ( OR=1.54 , 95 % CI=1.01 - 2.36 ) . No interaction with treatment was observed . A significant pharmacogenetic effect of the drug on negative mood while quitting also was noted . Smokers absent the A1 allele ( A2/A2 ) responded to the drug with a substantial reduction in negative affect , whereas those with the A1 allele showed no significant reduction in negative mood , F(1 , 130)=5.95 , p=.01 . These results are contrary to expectations and suggest that although A1s may have more difficulty quitting , adding venlafaxine does not improve abstinence or mood . However , the results for the A2s provide evidence for a genotype-specific response to a pharmacological intervention , which could have implication s for the development of future treatments OBJECTIVE Smoking is highly intractable , and the genetic influences on cessation are unclear . Identifying the genetic factors affecting smoking cessation could eluci date the nature of tobacco dependence , enhance risk assessment , and support development of treatment algorithms . This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking . METHOD In a community-based , crosssectional study ( N=5,216 ) and a r and omized comparative effectiveness smoking cessation trial ( N=1,073 ) , the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation ( self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial ) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244 . RESULTS The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample . In the smoking cessation trial , haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication . Haplotype interacted with treatment in affecting cessation success . CONCLUSIONS Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype . The high-risk haplotype increased the risk of cessation failure , and this increased risk was ameliorated by cessation pharmacotherapy . By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy , this work may support the development of personalized cessation treatments Smokers ( ⩾10 cigarettes per day , N=331 ) of European ancestry taking part in a double-blind placebo-controlled r and omized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of t and em repeats polymorphism in exon III of the dopamine D4 receptor gene . Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2 , 6 and 12 months after the end of treatment indicated that bupropion ( vs placebo ) predicted increased odds of abstinence . The main effect of Genotype was not significant . A Genotype × Treatment interaction ( P=0.005 ) showed that bupropion predicted increased odds of abstinence in long-allele carriers ( odds ratios (OR)=1.31 , P<0.0001 ) , whereas bupropion was not associated with abstinence among short-allele homozygotes ( OR=1.06 , P=0.23 ) . The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates ( P=0.01 ) and in analyses predicting continuous abstinence ( P's⩽0.054 ) . Bupropion may be more efficacious for smokers who carry the long allele , which is relevant to personalized pharmacogenetic treatment approaches Improving and targeting nicotine replacement therapy ( NRT ) are cost-effective strategies for reducing adverse health consequences for smokers . Treatment studies document the efficacy of precessation NRT and support important roles for level of nicotine dependence and precessation smoking reduction in successful quitting . However , prior work has not identified the optimal precessation dose or means for personalizing NRT . Genome-wide association has identified groups of genomic markers associated with successful quitting , allowing us to develop a v1.0 “ quit-success ” genotype score . We now report influences of v1.0 quit-success genotype score , level of dependence and precessation smoking reduction in a smoking cessation trial that examined effects of 21 versus 42 mg/24 h precessation NRT . Four hundred seventy-nine smokers were r and omized to 21 or 42 mg NRT , initiated 2 wks prior to target quit date s. We monitored self-reported abstinence and end-expired air carbon monoxide ( CO ) . Genotyping used Affymetrix arrays ( Santa Clara , CA , USA ) . The primary outcome was 10-wk continuous smoking abstinence . NRT dose , level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting . Successful abstinence also was predicted by CO reductions during precessation NRT . These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence , genotype scores and CO monitoring . These assessment s , taken together , can help match most smokers with optimal NRT doses and help rapidly identify some who may be better treated using other methods Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated , there is substantial variability among individuals in treatment response . We performed a systems-based c and i date gene study of 1295 single nucleotide polymorphisms ( SNPs ) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled r and omized clinical trial . Putative functional variants were supplemented with tagSNPs within each gene . We used global tests of main effects and treatment interactions , adjusting the P-values for multiple correlated tests . An SNP ( rs2072661 ) in the 3′ UTR region of the β2 nicotinic acetylcholine receptor subunit ( CHRNB2 ) has an impact on abstinence rates at the end of treatment ( adjusted P = 0.01 ) and after a 6-month follow-up period ( adjusted P = 0.0002 ) . This latter P-value is also significant with adjustment for the number of genes tested . Independent of treatment at 6-month follow-up , individuals carrying the minor allele have substantially decreased the odds of quitting ( OR = 0.31 ; 95 % CI 0.18–0.55 ) . Effect of estimates indicate that the treatment is more effective for individuals with the wild-type ( OR = 2.14 , 95 % CI 1.20–3.81 ) compared with individuals carrying the minor allele ( OR = 0.83 , 95 % CI 0.32–2.19 ) , although this difference is only suggestive ( P = 0.10 ) . Furthermore , this SNP demonstrated a role in the time to relapse ( P = 0.0002 ) and an impact on withdrawal symptoms at target quit date ( TQD ) ( P = 0.0009 ) . Overall , while our results indicate strong evidence for CHRNB2 in ability to quit smoking , these results require replication in an independent sample Despite effective therapies for smoking cessation , most smokers find quitting difficult and most successful quitters relapse . Considerable evidence supports a genetic risk for nicotine dependence ; however , less is known about the pharmacogenetics of smoking cessation . In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion , we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events . Subjects participated in r and omized , double-blind , placebo-controlled smoking cessation clinical trials , comparing varenicline , a nicotinic acetylcholine receptor ( nAChR ) partial agonist , with bupropion , a norepinephrine/dopamine reuptake inhibitor , and placebo . Primary analysis included 1175 smokers of European ancestry , and 785 single nucleotide polymorphisms from 24 genes , representing 254 linkage disequilibrium ( LD ) bins ( genes included nAChR subunits , additional varenicline-specific genes , and genes involved in nicotine or bupropion metabolism ) . For varenicline , continuous abstinence ( weeks 9–12 ) was associated with multiple nAChR subunit genes ( including CHRNB2 , CHRNA5 , and CHRNA4 ) ( OR=1.76 ; 95 % CI : 1.23–2.52 ) ( p<0.005 ) ; for bupropion , abstinence was associated with CYP2B6 ( OR=1.78 ; 95 % CI : 1.27–2.50 ) ( p<0.001 ) . Incidence of nausea was associated with several nAChR subunit genes ( OR=0.50 ; 95 % CI : 0.36–0.70 ) ( p<0.0001 ) and time to relapse after quitting was associated with HTR3B ( HR=1.97 ; 95 % CI : 1.45–2.68 ) ( p<0.0001 ) . These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response . Different loci are associated with varenicline vs bupropion response , suggesting that additional research may identify clinical ly useful markers to guide treatment decisions Background Lithium remains a first-line treatment in bipolar disorder , but individual response is variable . Previous studies have suggested that lithium response is a heritable trait . However , no genetic markers have been reproducibly identified . Methods Here we report the results of a genome-wide association study of lithium response in 2,563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics ( ConLiGen ) ; the largest attempted so far . Data from over 6 million common single nucleotide polymorphisms ( SNPs ) were tested for association with categorical and continuous ratings of lithium response of known reliability . Findings A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response ( rs79663003 : p=1·37 × 10−8 ; rs78015114 : p=1·31 × 10−8 ; rs74795342 : p=3·31 × 10−9 ; rs75222709 : p=3·50 × 10−9 ) . In an independent , prospect i ve study of 73 patients treated with lithium monotherapy for a period of up to two years , carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles ( p=0·03 , hazard ratio = 3·8 ) . Interpretation The response-associated region contains two genes coding for long non-coding RNAs ( lncRNAs ) , AL157359.3 and AL157359.4 . LncRNAs are increasingly appreciated as important regulators of gene expression , particularly in the CNS . Further studies are needed to establish the biological context of these findings and their potential clinical utility . Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder In this study , 147 smokers were r and omly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling ( 9 weekly sessions ) and transdermal nicotine replacement therapy ( 22 mg/day ) . Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting , with the daily dose titrated from 150 to 225 mg . in response to symptoms of negative affect and relapse . The results showed no main effect of treatment on abstinence . Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen . Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation . The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers , in addition to the expected benefits of nicotine replacement therapy and behavioral counseling Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study . Based on evidence suggesting their importance in stress reactivity and smoking , moderators studied were serotonin transporter gene ( 5-HTTLPR ) and dopamine D2 receptor gene ( DRD2 ) polymorphisms and personality traits related to negative affect ( NA ) . Smokers were r and omly assigned to quit smoking with nicotine or placebo patches . Financial incentives result ed in 80 % verified abstinence across the 44-day study . Individuals with 1 or 2 short alleles of 5-HTTLPR ( S carriers ) experienced larger increases in NA symptoms than did those without a short allele . Nicotine replacement therapy ( NRT ) alleviated anxiety only in S carriers . NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment ( when on the 21-mg patch ) ; however , A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch , while A2A2 individuals continued to benefit from NRT . The results suggest that the effects of genotype and treatment may vary across different duration s of abstinence , treatment doses , and genotypes Background : There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support . Methods : A r and omised controlled trial was performed in 26 UK general practice s. 925 smokers of ⩾10 cigarettes per day were r and omly allocated to basic or weekly support . All participants were seen before quitting , telephoned around quit day , and seen 1 and 4 weeks after the initial appointment ( basic support ) . Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts . 15 mg/16 h nicotine patches were given to all participants . The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4 , 12 , 26 and 52 weeks after quit day . Results : Of the 469 and 456 participants in the basic and weekly arms , the numbers ( % ) who quit and the percentage difference were 105 ( 22.4 % ) vs 102 ( 22.4 % ) , 0.1 % ( 95 % CI −5.3 % to 5.5 % ) at 4 weeks , 66 ( 14.1 % ) vs 52 ( 11.4 % ) , −2.6 % ( 95 % CI −6.9 % to 1.7 % ) at 12 weeks , 50 ( 10.7 % ) vs 40 ( 8.8 % ) , −1.9 % ( 95 % CI −5.7 % to 2.0 % ) at 26 weeks and 36 ( 7.7 % ) vs 30 ( 6.6 % ) , −1.1 % ( 95 % CI −4.4 % to 2.3 % ) at 52 weeks . Conclusions : The absolute quit rates achieved are those expected from nicotine replacement alone , implying that neither basic nor weekly support were effective . Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately , and those in need of support should be referred to specialists Pharmacogenetic clinical trials seek to identify genetic modifiers of treatment effects . When a trial has collected data on many potential genetic markers , a first step in analysis is to screen for evidence of pharmacogenetic effects by testing for treatment‐by‐marker interactions in a statistical model for the outcome of interest . This approach is potentially problematic because ( i ) individual significance tests can be overly sensitive , particularly when sample sizes are large ; and ( ii ) st and ard significance tests fail to distinguish between markers that are likely , on biological grounds , to have an effect , and those that are not . One way to address these concerns is to perform Bayesian hypothesis tests [ Berger ( 1985 ) Statistical decision theory and Bayesian analysis . New York : Springer ; Kass and Raftery ( 1995 ) J Am Stat Assoc 90:773–795 ] , which are typically more conservative than st and ard uncorrected frequentist tests , less conservative than multiplicity‐corrected tests , and make explicit use of relevant biological information through specification of the prior distribution . In this article we use a Bayesian testing approach to screen a panel of genetic markers recorded in a r and omized clinical trial of bupropion versus placebo for smoking cessation . From a panel of 59 single‐nucleotide polymorphisms ( SNPs ) located on 11 c and i date genes , we identify four SNPs ( one each on CHRNA5 and CHRNA2 and two on CHAT ) that appear to have pharmacogenetic relevance . Of these , the SNP on CHRNA5 is most robust to specification of the prior . An unadjusted frequentist test identifies seven SNPs , including these four , none of which remains significant upon correction for multiplicity . In a panel of 43 r and omly selected control SNPs , none is significant by either the Bayesian or the corrected frequentist test . © 2007 Wiley‐Liss , Context Do certain forms of nicotine replacement therapy work better than others and , if so , in whom ? Contribution This r and omized trial of 299 treatment-seeking smokers found similar 6-month abstinence rates between smokers receiving behavioral counseling and 8 weeks of therapy with either nicotine nasal spray ( 12 % ) or transdermal nicotine ( 15 % ) . Subgroup analyses suggested that highly dependent , obese , and nonwhite smokers achieved higher abstinence rates with nasal spray . Low to moderately dependent , nonobese , and white smokers achieved higher abstinence rates with transdermal nicotine . Caution s Tailoring nicotine replacement therapy on the basis of characteristics of smokers is an intriguing strategy but has not yet been tested . The Editors Nicotine replacement therapy is recommended as a first-line treatment for tobacco dependence ( 1 ) . Although use of nicotine replacement therapy can double a person 's odds of quitting smoking , as many as 70 % to 80 % of smokers receiving treatment do not achieve long-term abstinence ( 2 - 5 ) . Nicotine replacement therapy is widely used ; however , empirical data are insufficient to guide practitioners in selecting a particular form of treatment for individual patients with tobacco dependence ( 1 ) . In lieu of such evidence , the most rational approach has been to base the choice of pharmacotherapy on the patient 's previous treatment experiences and preferences ( 6 ) . However , recent data suggest that smokers ' past experiences and preferences have little bearing on the outcome of nicotine replacement therapy ( 7 ) . Our goal was to evaluate the comparative efficacy of transdermal nicotine and nicotine nasal spray and to identify pretreatment clinical characteristics that predict treatment outcome . In addition , to suggest factors that may be useful for individualizing nicotine replacement therapy , we examined predictors of treatment outcome by using subgroup analyses . These 2 forms of nicotine replacement therapy were selected on the basis of their differing pharmacokinetic and pharmacodynamic properties . After administration of transdermal nicotine , levels of nicotine rise slowly and then plateau within 4 to 6 hours ( 8) . This profile is believed to be optimal for alleviating withdrawal symptoms and perhaps reducing positive reinforcement from nicotine when subsequent exposure to tobacco occurs ( that is , a brief lapse or slip ) ( 9 , 10 ) . In contrast , nicotine nasal spray produces rapid peak venous levels of nicotine , which lead to rewarding effects that more closely approximate those achieved from cigarette smoking ( 9 , 11 , 12 ) . Methods Participants were enrolled at Georgetown University ( Washington , DC ) and the University of Pennsylvania ( Philadelphia , Pennsylvania ) . The institutional review boards from both universities approved the research procedures . Figure 1 shows the flow of participants through the enrollment , treatment , and follow-up phases of the trial . Figure 1 . Flow diagram of trial participation . Smokers responding to local media advertisements for free smoking cessation treatment and to physician referrals were screened for eligibility and recruited from February 2000 through March 2002 . Eligible persons were current cigarette smokers 18 years of age or older who had smoked 10 or more cigarettes per day for the previous 12 months . Exclusion criteria were pregnancy or lactation , uncontrolled hypertension , unstable angina , heart attack or stroke within the previous 6 months , current treatment or recent diagnosis of cancer , drug or alcohol dependence , current diagnosis or history of a psychotic disorder , or current use of bupropion or nicotine-containing products other than cigarettes . Study Design and Treatment Procedures This was a r and omized , open-label clinical trial of transdermal nicotine versus nicotine nasal spray for smoking cessation . R and omization was determined by using a computer-generated r and omization scheme operated by a senior data manager ; stratification was done by study site . Allocation to treatment could not be concealed from the counselors or the study assistants who delivered the medication to patients after preparation at the research pharmacy . All participants received 7 sessions of st and ardized behavioral group counseling that included instruction in the management of smoking triggers , relapse prevention , and stress management techniques . The behavioral counseling sessions , which occurred in the evening , lasted approximately 1.5 hours each and included approximately 10 to 14 members per group . As reported previously ( 13 ) , 70 % of participants completed all 7 sessions , and differences in completion rates by study site were not statistically significant . At each site , two counselors with master 's degrees led an equal number of groups receiving either transdermal nicotine or nicotine nasal spray therapy and received weekly supervision to ensure protocol adherence . Nicotine nasal spray therapy ( Nicotrol , Pharmacia and Upjohn , Helsingborg , Sweden ) was initiated on the target quit date ( week 3 ) and was delivered over an 8-week period . At the second counseling session ( week 2 ) , participants were shown how to deliver a 1.0-mg dose ( 0.5-mg spray in each nostril ) and how to use nicotine nasal spray 8 to 40 times per day ( with a maximum of 5 doses/h ) beginning on the target quit date . After 4 weeks of use , participants were instructed to taper their nicotine nasal spray dose by one third for a 2-week period and then by another third for the final 2 weeks of treatment . Participants used transdermal nicotine ( Nicoderm CQ , GlaxoSmithKline , Research Triangle Park , North Carolina ) over an 8-week treatment period , beginning with the morning of the target quit date ( week 3 ) . A 24-hour , tapered-dose formulation was used : 4 weeks at 21 mg , 2 weeks at 14 mg , and 2 weeks at 7 mg . To assess smoking status , we conducted telephone interviews at the end of treatment ( 8 weeks after the target quit date ) and 6 months after the target quit date ; a st and ard timeline follow-back method was used ( 14 ) . Interviewers were blinded to study group assignment . Participants who reported complete abstinence ( not even a puff of a cigarette ) for at least 7 days before the assessment were asked to complete an in-person visit for biochemical verification of abstinence within 1 to 2 weeks after the follow-up interview . Adverse events were self-reported by using a weekly checklist that queried the severity of 17 common side effects associated with nicotine replacement therapy ( for example , rash with transdermal nicotine ) . Research assistants evaluated the completed checklist before each counseling visit and review ed it with the study physicians and participants , as needed . Measurements Predictors On the basis of previous research and ease of assessment , we selected the following variables as predictors : sex , ethnicity , education , body mass index ( BMI ) , nicotine dependence , and depression symptoms ( 15 - 18 ) . We used the Fagerstrom Test for Nicotine Dependence ( 19 ) to measure tobacco dependence ; a cutoff score of 7 or greater was used to classify participants as highly nicotine dependent ( 20 ) . The Center for Epidemiologic Studies Depression Scale ( CES-D ) was used to assess the severity of depression symptoms ; a score 16 or greater was used to identify clinical symptoms of depression ( 21 ) . Height and weight were measured at the medical screening visit . Body mass index was calculated by dividing weight in kilograms by height in millimeters ( squared ) , and obesity was defined according to recommendations of the National Institutes of Health ( BMI 30 kg/m2 ) ( 22 ) . Treatment Monitoring Participants recorded their daily use of nicotine replacement therapy . Those assigned to transdermal nicotine recorded their daily application of patches , and those assigned to nicotine nasal spray recorded the number of doses per day . Because use of nicotine replacement therapy may be confounded with smoking status ( that is , participants may discontinue nicotine replacement therapy if they have relapses ) , we focused on average use during the first 2 weeks of treatment . We calculated the percentage of cotinine replacement from treatment by dividing participants ' plasma cotinine levels after 1 week of treatment by their pretreatment plasma cotinine levels ( 23 ) . These time points were selected to coincide with a period of regular smoking and with steady-state cotinine levels achieved after treatment ( 23 ) . Cotinine levels were analyzed by using gas chromatography with nitrogen phosphorus detection , modified for analysis by using a capillary gas chromatography column ( 24 ) . Outcomes We used prolonged abstinence as the primary outcome measure and point prevalence as the secondary measure ( 25 ) . For prolonged abstinence , relapse was defined as 7 consecutive days of smoking at any time during the follow-up period . Because the prolonged abstinence measurement period extends from the target quit date to 6-month follow-up , biochemical verification for this period , by definition , is not possible . The point prevalence measure required 7 days of continuous abstinence immediately before the follow-up point , which was confirmed by a carbon monoxide reading of less than 10 parts per million ( ppm ) ( 26 ) . ( Of note , of the 65 participants who self-reported 7 days of abstinence and provided a carbon monoxide sample , 15 [ 23 % ] had a carbon monoxide level 10 ppm ) . Thus , for prolonged abstinence , brief relapses or slips ( that is , any smoking at all , even a puff ) were allowed , whereas the point prevalence measure allowed no lapses during the 7 days before each follow-up ( 25 ) . For descriptive purpose s , we also assessed rates of continuous abstinence under the most stringent criterion ( not even a puff ) from target quit date to 6-month follow-up ( not biochemically verified ) . In intention-to-treat analyses , we presumed that those who dropped out or were otherwise lost to follow-up had had relapses . Statistical Analysis We calculated that a sample size of at Smokers of European ancestry ( n=720 ) who participated in a double-blind , r and omised , placebo-controlled trial of transdermal nicotine replacement therapy , were genotyped for two functional polymorphisms ( variable number of t and em repeats ( VNTR ) and a C to T transition at position –521 ( C-521 T ) ) in the dopamine D4 receptor gene ( DRD4 ) gene . Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism . For the DRD4 VNTR models , the main effect of treatment was significant at both 12-week ( P=0.001 ) and 26-week ( P=0.006 ) follow-ups , indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo . The main effect of DRD4 VNTR genotype was associated with abstinence at 12-week follow-up ( P=0.034 ) , with possession of one or more copies of the long allele associated with reduced likelihood of cessation ( 17 vs 23 % ) , but this effect was not observed at 26-week follow-up . For the DRD4 C-521 T models , no main effect or interaction terms involving genotype were retained in the models at either 12- or 26-week follow-up . These data are consistent with observations from studies of the DRD2 gene that genetic variants related to relatively decreased dopaminergic tone in the mesocorticolimbic system are associated with increased risk for relapse to smoking following a cessation attempt AIMS To evaluate the associations of treatment and an additive genetic efficacy score ( AGES ) based on dopamine functional polymorphisms with time to first smoking lapse and point prevalence abstinence at end of treatment among participants enrolled into two r and omized clinical trials of smoking cessation therapies . DESIGN Double-blind pharmacogenetic efficacy trials r and omizing participants to active or placebo bupropion . Study 1 also r and omized participants to cognitive-behavioral smoking cessation treatment ( CBT ) or this treatment with CBT for depression . Study 2 provided st and ardized behavioural support . SETTING Two hospital-affiliated clinics ( study 1 ) , and two university-affiliated clinics ( study 2 ) . PARTICIPANTS A total of 792 self-identified white treatment-seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year . MEASUREMENTS Age , gender , Fagerström Test for Nicotine Dependence , dopamine pathway genotypes ( rs1800497 [ ANKK1 E713 K ] , rs4680 [ COMT V158 M ] , DRD4 exon 3 variable number of t and em repeats polymorphism [ DRD4 VNTR ] , SLC6A3,3 ' VNTR ) analyzed both separately and as part of an AGES , time to first lapse and point prevalence abstinence at end of treatment . FINDINGS Significant associations of the AGES ( hazard ratio [ HR ] = 1.10 , 95 % confidence interval [ CI ] = 1.06 - 1.14 , P = 0.009 ) and of the DRD4 VNTR ( HR = 1.29 , 95 % CI = 1.17 - 1.41 , P = 0.0073 ) were observed with time to first lapse . A significant AGES by pharmacotherapy interaction was observed ( β st and ard error = -0.18 [ 0.07 ] , P = 0.016 ) , such that AGES predicted risk for time to first lapse only for individuals r and omized to placebo . CONCLUSIONS A score based on functional polymorphisms relating to dopamine pathways appears to predict lapse to smoking following a quit attempt , and the association is mitigated in smokers using bupropion AIMS Tobacco dependence treatments achieve abstinence rates of 25 - 30 % at 1 year . Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder . The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age , and to determine if gender differences in efficacy existed . DESIGN Open r and omized clinical trial . SETTING A free-st and ing , smoking treatment research clinic . PARTICIPANTS A total of 402 smokers of > or = 10 cigarettes per day , all 50 years of age or older . INTERVENTION Participants completed a 12-week treatment that included group counseling , nicotine replacement therapy ( NRT ) and bupropion . Participants , independent of smoking status , were then assigned r and omly to follow-up conditions : ( i ) st and ard treatment ( ST ; no further treatment ) ; ( ii ) extended NRT ( E-NRT ; 40 weeks of nicotine gum availability ) ; ( iii ) extended cognitive behavioral therapy ( E-CBT ; 11 cognitive behavioral sessions over a 40-week period ) ; or ( iv ) E-CBT plus E-NRT ( E-combined ; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability ) . MEASUREMENTS Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24 , 52 , 64 and 104 . FINDINGS The most clinical ly important findings were significant main effects for treatment condition , time and the treatment x time interaction . The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [ ( week 24 ( 58 % ) , 52 ( 55 % ) , 64 ( 55 % ) and 104 ( 55 % ) ] , and was significantly more effective than E-NRT and ST across that period . No other treatment condition was significantly different to ST . No effects for gender were found . CONCLUSIONS Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women . NRT does not add to the efficacy of extended CBT , and may hamper its efficacy . Research is needed to determine if these results can be replicated in a sample with a greater range of ages , and improved upon with the addition of medications other than NRT BACKGROUND Smoking remains the primary preventable cause of death and illness in the U.S. Effective , convenient treatment programs are needed to reduce smoking prevalence . PURPOSE This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline . METHODS Current treatment-seeking smokers ( n=1202 ) were recruited from a large healthcare organization between October 2006 and October 2007 . Eligible participants were r and omized to one of three smoking-cessation interventions : web-based counseling ( n=401 ) ; proactive telephone-based counseling ( PTC ; n=402 ) ; or combined PTC and web counseling ( n=399 ) . All participants received a st and ard 12-week FDA -approved course of varenicline . Self-report determined the primary outcomes ( 7-day point prevalent abstinence at 3- and 6-month follow-ups ) ; the number of days varenicline was taken ; and treatment-related symptoms . Behavioral measures determined utilization of both the web- and Phone-based counseling . RESULTS Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months ( 38.9 % , 48.5 % , 43.4 % ) and at 6 months ( 30.7 % , 34.3 % , 33.8 % ) for the web , PTC , and PTC-web groups , respectively . The PTC group had a significantly higher percentage of abstinence than the web group at 3 months ( OR=1.48 , 95 % CI=1.12 , 1.96 ) , but no between-group differences in abstinence outcomes were seen at 6 months . CONCLUSIONS Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence , but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline Bupropion is indicated to promote smoking cessation . Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite , hydroxybupropion . We measured plasma bupropion and its metabolite levels in a double‐blind , placebo controlled , r and omized smoking‐cessation trial . Among the treatment‐adherent individuals , higher hydroxybupropion concentrations ( per μg/ml ) result ed in better smoking‐cessation outcomes ( week 3 , 7 , and 26 odds ratio ( OR ) = 2.82 , 2.96 , and 2.37 , respectively , P = 0.005–0.040 ) ; this was not observed with bupropion levels ( OR = 1.00–1.03 , P = 0.59–0.90 ) . Genetic variation in CYP2B6 , the enzyme that metabolizes bupropion to hydroxybupropion , was identified as a significant source of variability in hydroxybupropion formation . Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation , and that variability in response to bupropion treatment is related to variability in CYP2B6‐mediated hydroxybupropion formation . These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion 's cessation outcomes AIM Approximately 50 % of African American smokers are light smokers ( smoke < or = 10 cigarettes a day ) . The prevalence of light smoking in the United States is increasing , yet there has not been a single smoking cessation clinical trial targeting light smokers . The purpose of this 2 x 2 factorial , r and omized clinical trial was to evaluate the efficacy of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) for African American light smokers . DESIGN Participants were assigned r and omly to one of four study arms : 2 mg nicotine gum plus health education ( HE ) ; 2 mg nicotine gum plus motivational interviewing ( MI ) ; placebo gum plus HE ; and placebo gum plus MI . PARTICIPANTS AND SETTING A total of 755 African American light smokers ( 66 % female , mean age = 45 ) were enrolled at a community health center over a 16-month period . INTERVENTION AND MEASUREMENTS Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study . Biochemical measures included expired carbon monoxide ( CO ) and serum and salivary cotinine . FINDINGS Seven-day quit rates for nicotine gum were no better than for the placebo group ( 14.2 % versus 11.1 % , P = 0.232 ) at 6 months . However , a counseling effect emerged , with HE performing significantly better than MI ( 16.7 % versus 8.5 % , P < 0.001 ) . These results were consistent across outcome time-points ( weeks 1 , 8 , and 26 ) . CONCLUSIONS Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation . Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit A r and omized double-blind , active controlled , parallel group , multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment ( under Investigational Device Exemption 69,185 ) . The concept for a reduced-nicotine cigarette design ed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine , but also on weaning from the habitual sensory and behavioral reinforcement of smoking . Treatment consisted of Quest br and of cigarettes ( Quest 1 , 2 , and 3 ) , which respectively deliver 0.59+/-0.06 , 0.3+/-0.05 , and less than 0.05 mg nicotine , either alone or in combination with nicotine replacement therapy ( NRT ) . The primary endpoint was 4 weeks of continuous abstinence ( Weeks 7 - 10 ) , with additional follow-up at 3 and 6 months . Adult men and women smokers ( N = 346 ) , motivated to quit , were r and omized to one of three treatment groups : Quest plus NRT ( NRT pretreatment 2 weeks before , and NRT after the quit date ) , Quest plus placebo patch , or active control plus NRT ( conventional cigarette , followed by NRT after quit date ) . Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence ( 32.8 % vs. 21.9 % ) . Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT ( 16.4 % vs. 21.9 % ) . No serious adverse events were attributable to the investigational product . Quest plus NRT offers promise as a new smoking cessation treatment Objective To evaluate the association of nicotinic acetylcholine receptor ( nAChR ) single nucleotide polymorphism ( SNP ) with 7-day point prevalence abstinence ( abstinence ) in r and omized clinical trials of smoking cessation therapies in individuals grouped by pharmacotherapy r and omization to inform the development of personalized smoking cessation therapy . Material s and methods We quantified association of four SNPs at three nAChRs with abstinence in eight r and omized clinical trials . Participants were 2633 outpatient treatment-seeking , self-identified European ancestry individuals smoking at least 10 cigarettes/day , recruited through advertisement , prescribed pharmacotherapy , and provided with behavioral therapy . Interventions included nicotine replacement therapy ( NRT ) , bupropion , varenicline , placebo ( PLA ) , or combined NRT and bupropion , and five modes of group and individual behavioral therapy . Outcome measures tested in multivariate logistic regression were end of treatment and 6 month ( 6MO ) abstinence , with demographic , behavioral , and genetic covariates . Results ‘ Risk ’ alleles previously associated with smoking heaviness were significantly ( P<0.05 ) associated with reduced abstinence in the PLA pharmacotherapy group ( PG ) at 6MO [ for rs588765 , odds ratio ( 95 % confidence interval ) 0.41 ( 0.17–0.99 ) ] , and at end of treatment and at 6MO [ for rs1051730 , 0.42 ( 0.19–0.93 ) and 0.31 ( 0.12–0.80 ) ] , and with increased abstinence in the NRT PG at 6MO [ for rs588765 , 2.07 ( 1.11–3.87 ) and for rs1051730 , 2.54 ( 1.29–4.99 ) ] . We observed significant heterogeneity in rs1051730 effects ( F=2.48 , P=0.021 ) between PGs . Conclusion chr15q25.1 nAChR SNP risk alleles for smoking heaviness significantly increase relapse with PLA treatment and significantly increase abstinence with NRT . These SNP – PG associations require replication in independent sample s for validation , and testing in larger sample sizes to evaluate whether similar effects occur in other PGs This study examined the role of dopaminergic genes in prospect i ve smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial . Smokers of European ancestry ( N=418 ) provided blood sample s for genetic analysis and received either bupropion or placebo ( 10 weeks ) plus counseling . Assessment s included the dopamine D2 receptor ( DRD2 ) genotype , dopamine transporter ( SLC6A3 ) genotype , demographic factors , and nicotine dependence . Smoking status was verified at the end of treatment ( EOT ) and at 6-month follow-up . The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT , independent of treatment condition . Such effects were no longer significant at 6-month follow-up , however . These results provide the first evidence from a prospect i ve clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase Objective To estimate the “ real-world ” effectiveness of commonly used aids to smoking cessation in Engl and by using longitudinal data . Patients and Methods We conducted a prospect i ve cohort study in 1560 adult smokers who participated in an English national household survey in the period from November 2006 to March 2012 , responded to a 6-month follow-up survey , and made at least 1 quit attempt between the 2 measurements . The quitting method was classified as follows : ( 1 ) prescription medication ( nicotine replacement therapy [ NRT ] , bupropion , or varenicline ) in combination with specialist behavioral support delivered by a National Health Service Stop Smoking Service ; ( 2 ) prescription medication with brief advice ; ( 3 ) NRT bought over the counter ; ( 4 ) none of these . The primary outcome measure was self-reported abstinence up to the time of the 6-month follow-up survey , adjusted for key potential confounders including cigarette dependence . Results Compared with smokers using none of the cessation aids , the adjusted odds of remaining abstinent up to the time of the 6-month follow-up survey were 2.58 ( 95 % CI , 1.48 - 4.52 ) times higher in users of prescription medication in combination with specialist behavioral support and 1.55 ( 95 % CI , 1.11 - 2.16 ) times higher in users of prescription medication with brief advice . The use of NRT bought over the counter was associated with a lower odds of abstinence ( odds ratio , 0.68 ; 95 % CI , 0.49 - 0.94 ) . Conclusion Prescription medication offered with specialist behavioral support and that offered with minimal behavioral support are successful methods of stopping cigarette smoking in Engl and Several studies have documented the effectiveness of bupropion for smoking cessation , yet little is known about the mechanisms by which it facilitates abstinence . In this placebo-controlled r and omized trial . We examined whether bupropion 's effects on cessation were mediated by changes in withdrawal and /or negative or positive affect ( PA ) . Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo , plus behavioral counseling . Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models . Cotinine-verified 7-day point prevalence cessation rates at the end of treatment ( 8-weeks post quit date ) were 48 % for bupropion and 29 % for placebo ( P=0.001 ) . There were significant treatment effects on withdrawal and negative affect ( NA ) ; however , only change in NA predicted cessation . In a path model , change in NA was a significant mediator of bupropion 's effects on cessation . However , the proportion of variance accounted for by this mediator was small , suggesting that other unmeasured factors play an important role . Laboratory-based paradigms may be useful to identify other mediators of bupropion 's effects , thereby pointing to mechanisms of effect that can be bolstered in future treatment studies UNLABELLED PRIMARY AIM : Examine the effectiveness of extended cognitive behavior therapy ( CBT ) in promoting longer-term smoking abstinence . DESIGN Open-label treatment phase followed by extended treatment phase . R and omization conducted prior to entry into open-label treatment phase ; analysis based on intention-to-treat to avoid threat of selection bias . SETTING Community smoking cessation clinic . PARTICIPANTS A total of 304 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . INTERVENTION Open-label ( 8 weeks ) : all participants received bupropion SR , nicotine patch , CBT . Extended treatment ( 12 weeks ) : participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support . MEASUREMENTS Seven-day point prevalence abstinence , expired-air carbon monoxide . RESULTS At week 20 follow-up , CBT produced a higher 7-day point prevalence abstinence rate : 45 % versus 29 % , P = 0.006 ; at 52 weeks the difference in abstinence rates ( 31 % versus 27 % ) was not significant . History of depression was a moderator of treatment . Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy ( P < 0.05 ) . CONCLUSION The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term . At present , the minimum duration of therapy is unknown BACKGROUND Although bupropion is efficacious for smoking cessation , only a minority of smokers are able to quit . Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers . We investigated variants in the catechol-O-methyltransferase ( COMT ) gene in a smoking cessation trial of bupropion . METHODS A double-blind , placebo-controlled , 10-week trial of bupropion and counseling ( with a 6-month follow-up period ) was conducted at two university-based smoking cessation research programs . Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date . RESULTS At the end of the treatment phase , statistically significant interaction effects indicated that COMT haplotypes of two SNPs ( rs737865 and rs165599 ) predicted the efficacy of bupropion compared with placebo . This interaction effect was attenuated at 6-month follow-up . CONCLUSIONS COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation . European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment . Small numbers of some COMT haplotypes limit interpretation of response . If study findings are confirmed in additional large studies , COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation OBJECTIVE To determine the relationship between joint variation in 2 dopaminergic genes and the likelihood of nonsmoking following treatment with bupropion sustained release ( SR ) . DESIGN Three hundred twenty-three participants in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up were genotyped for variants of dopamine receptor gene DRD2 and dopamine transporter SLC6A3 . MAIN OUTCOME MEASURES Self-reported 7-day point prevalence of nonsmoking . RESULTS Neither genotype alone was associated with 7-day point-prevalent nonsmoking at the 12-month follow-up . However , in the presence of the DRD2 A1 allele , SLC6A3 status was significantly associated with the likelihood of nonsmoking at the 12-month follow-up ( individuals with DRD2 A1 + and SLC6A3 9- were more likely to be smoking ) . In the absence of the DRD2 A1 allele , the association between SLC6A3 status and nonsmoking was nonsignificant . CONCLUSION Although these results are suggestive , a more compelling test is needed of the hypothesis that dopaminergic gene interaction underlies , in part , the likelihood of smoking following treatment with bupropion SR . Most likely this will come from larger studies involving prospect i ve r and omization to treatment based on genotype CONTEXT Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies , yet such evidence is needed to make informed decisions about their clinical use . OBJECTIVE To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled , head-to-head comparisons . DESIGN A r and omized , double-blind , placebo-controlled clinical trial . SETTING Two urban research sites . PATIENTS One thous and five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking . Participants were excluded if they reported using any form of tobacco other than cigarettes ; current use of bupropion ; having a current psychosis or schizophrenia diagnosis ; or having medical contraindications for any of the study medications . INTERVENTIONS Participants were r and omized to 1 of 6 treatment conditions : nicotine lozenge , nicotine patch , sustained-release bupropion , nicotine patch plus nicotine lozenge , bupropion plus nicotine lozenge , or placebo . In addition , all participants received 6 individual counseling sessions . MAIN OUTCOME MEASURES Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date ( postquit ) , end of treatment ( 8 weeks postquit ) , and 6 months postquit . Other outcomes were initial cessation , number of days to lapse , number of days to relapse , and latency to relapse after the first lapse . RESULTS All pharmacotherapies differed from placebo when examined without protection for multiple comparisons ( odds ratios , 1.63 - 2.34 ) . With such protection , only the nicotine patch plus nicotine lozenge ( odds ratio , 2.34 , P < .001 ) produced significantly higher abstinence rates at 6-month postquit than did placebo . CONCLUSION While the nicotine lozenge , bupropion , and bupropion plus lozenge produced effects that were comparable with those reported in previous research , the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation We analyzed pooled data from two comparable r and omized placebo-controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available . A total of 722 smokers across the two trials were r and omized to 10 weeks of sustained-release bupropion hydrochloride or placebo . General estimating equation analysis demonstrated a significant gene x drug interaction ( B = 0.87 , SE = 0.34 , p = .009 ) . Smokers with the A2/A2 genotype using bupropion were more than three times as likely , relative to placebo , to be abstinent at end of treatment ( 35.2 % vs. 15.1 % ; OR = 3.25 , 95 % CI 2.00 - 5.28 ) and at 6 months of follow-up ( 26.7 % vs. 12.2 % ; OR = 2.81 , 95 % CI 1.66 - 4.77 ) , which was attenuated by 12 months ( 16.3 % vs. 10.7 % ; OR = 1.70 , 95 % CI 0.95 - 3.05 ) . We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes . These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype BACKGROUND Tobacco dependence is a chronic , relapsing condition that may require extended treatment . OBJECTIVE To assess whether extended- duration transdermal nicotine therapy increases abstinence from tobacco more than st and ard- duration therapy in adult smokers . DESIGN Parallel r and omized , placebo-controlled trial from September 2004 to February 2008 . Participants and all research personnel except the data base manager were blinded to r and omization . ( Clinical Trials.gov registration number : NCT00364156 ) SETTING Academic center . PARTICIPANTS 568 adult smokers . INTERVENTION In an unstratified small block-r and omization scheme , participants were r and omly assigned to st and ard therapy ( Nicoderm CQ [ GlaxoSmithKline , Research Triangle Park , North Carolina ] , 21 mg , for 8 weeks and placebo for 16 weeks ) or extended therapy ( Nicoderm CQ , 21 mg , for 24 weeks ) . MEASUREMENTS The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52 . Secondary outcomes were continuous and prolonged abstinence , lapse and recovery events , cost per additional quitter , and side effects and adherence . RESULTS At week 24 , extended therapy produced higher rates of point-prevalence abstinence ( 31.6 % vs. 20.3 % ; odds ratio , 1.81 [ 95 % CI , 1.23 to 2.66 ] ; P = 0.002 ) , prolonged abstinence ( 41.5 % vs. 26.9 % ; odds ratio , 1.97 [ CI , 1.38 to 2.82 ] ; P = 0.001 ) , and continuous abstinence ( 19.2 % vs. 12.6 % ; odds ratio , 1.64 [ CI , 1.04 to 2.60 ] ; P = 0.032 ) versus st and ard therapy . Extended therapy reduced the risk for lapse ( hazard ratio , 0.77 [ CI , 0.63 to 0.95 ] ; P = 0.013 ) and increased the chances of recovery from lapses ( hazard ratio , 1.47 [ CI , 1.17 to 1.84 ] ; P = 0.001 ) . Time to relapse was slower with extended versus st and ard therapy ( hazard ratio , 0.50 [ CI , 0.35 to 0.73 ] ; P < 0.001 ) . At week 52 , extended therapy produced higher quit rates for prolonged abstinence only ( P = 0.027 ) . No differences in side effects and adverse events between groups were found at the extended-treatment assessment . LIMITATION The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment , and differences in adherence across treatment groups were detected . CONCLUSION Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24 , reduced the risk for smoking lapses , and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy . PRIMARY FUNDING SOURCE National Institutes of Health AIMS The primary aim of this study was to compare the efficacy of smoking cessation treatment using a combination of nicotine patch and bupropion vs. nicotine patch and placebo bupropion . A secondary aim was to investigate whether the efficacy of bupropion is moderated by belief about whether one is receiving active or placebo medication . METHODS Participants were recruited from a residential substance abuse treatment program and the community . We r and omly assigned 148 smokers with between 2 and 12 months of alcohol abstinence to nicotine patch plus bupropion or nicotine patch plus placebo . All participants also received seven counseling sessions . RESULTS At follow up , differences between medication conditions were not significant . Seven-day point prevalence quit rates in the patch plus bupropion vs. patch plus placebo conditions at week 24 were 6 % and 11 % , respectively . Differences between groups on prolonged abstinence and time to first smoking lapse were also not significant . However , among participants who received bupropion , those who accurately " guessed " that they were receiving bupropion were more likely to remain abstinent than those who incorrectly believed they were receiving placebo . CONCLUSIONS Findings do not support combining nicotine patch and bupropion for smoking cessation in this population . However , findings support previous studies suggesting the importance of assessing the blind in smoking cessation studies and its possible moderating effect on medication efficacy . Future directions for enhancing smoking cessation outcome in these smokers include investigations of intensive behavioral and pharmacological interventions , including studies of potential interactions between individual genetic differences and medication efficacy AIMS We investigated whether variants in the serotonin transporter gene ( SLC6A4 ) influence smoking cessation rates using antidepressant therapy ( i.e. bupropion and nortriptyline ) . DESIGN Pharmacogenetic ( secondary ) analysis of a r and omized , placebo-controlled efficacy trial of bupropion and nortriptyline for smoking cessation . SETTING Single-centre study , Maastricht University , the Netherl and s. PARTICIPANTS A total of 214 of 255 ( 84 % ) current daily smokers participating in a r and omized controlled efficacy trial . MEASUREMENTS Subjects were genotyped for three functional variants in SLC6A4 ( 5-HTTLPR , STin2 , rs25531 ) . Primary outcome measures were prolonged abstinence from weeks 4 - 12 , 4 - 26 and 4 - 52 . Secondary outcome measures included 7-day point prevalence abstinence at weeks 4 , 12 , 26 and 52 . FINDINGS Carriers of the 5-HTTLPR high-activity L-variant had higher prolonged cessation rates with bupropion than placebo [ odds ratio ( OR ) = 1.44 , 95 % confidence interval ( CI ) = 1.01 - 2.05 , P = 0.04 ] . Combining the three variants result ed in increased prolonged cessation rates for both bupropion and nortriptyline among carriers of four to five high-activity variants ( bupropion : OR = 2.00 , 95 % CI = 1.21 - 3.29 , P = 0.01 ; nortriptyline : OR = 1.91 , 95 % CI = 1.02 - 3.56 , P = 0.04 ) . Similar results were found for point prevalence abstinence . CONCLUSIONS Bupropion and nortriptyline seem to be more effective in smoking cessation among SLC6A4 high-activity variant carriers , probably by blocking the increased serotonin transporter activity , thereby increasing serotonin levels . Prospect i ve studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes We examined whether a pretreatment phenotypic marker of nicotine metabolism rate ( NMR ) predicts successful smoking cessation with bupropion . Smokers ( N = 414 ) were tested for pretreatment NMR , based on the ratio of 3′‐hydroxycotinine/cotinine derived during smoking , before entering a placebo‐controlled r and omized trial of bupropion plus counseling . At the end of the 10‐week treatment phase , slow metabolizers ( 1st NMR quartile ) had equivalent quit rates with placebo or bupropion ( 32 % ) . Fast metabolizers ( 4th NMR quartile ) had low quit rates with placebo ( 10 % ) , and these were enhanced significantly by bupropion ( 34 % ) . Smokers in the 2nd quartile ( placebo : 25 % , bupropion : 30 % ) and the 3rd quartile ( placebo : 20 % , bupropion : 30 % ) did not benefit significantly from bupropion . At the 6‐month follow‐up , the relationship between the NMR and quitting remained similar , but was no longer statistically significant . A pretreatment assessment of NMR may identify smokers who are most and least likely to benefit from treatment with bupropion for smoking cessation Objectives To determine whether there were differential quit rates between African Americans ( AA ) and European Americans with the experimental treatment naltrexone , and examine the role of genetic ancestry on these outcomes among AAs . Methods Data from a previous r and omized trial of 315 smokers to naltrexone versus placebo were reanalyzed using West African ( WA ) genetic ancestry to define sub population s. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates , by race and WA ancestry . Results Among European Americans ( n=136 ) , naltrexone significantly increased quit rates at 4 weeks ( 62 vs. 43 % , P=0.03 ) with directional , but not statistically significant effects at 12 weeks ( 30 vs. 18 % , P=0.12 ) . In contrast , among the AAs ( n=95 ) , quit rates did not differ between naltrexone and placebo groups at either interval ( 4 weeks : 43 vs. 32 % , P=0.27 ; 12 weeks : 22 vs. 18 % , P=0.60 ) . A median split was conducted in AAs for WA ancestry . Among AAs with low WA ancestry , quit rates were significantly higher with naltrexone compared with placebo ( 60 vs. 27 % , P=0.03 ) . There was no advantage in quit rates with naltrexone for the high WA ancestry group . Conclusion Naltrexone efficacy for smoking cessation varies across AA individuals with different levels of WA ancestry . These results suggest that genetic background may partially explain racial differences in drug response BACKGROUND CYP2B6 is the primary enzyme involved in bupropion ( Zyban ; GlaxoSmithKline , Research Triangle Park , North Carolina ) metabolism . Genetic polymorphisms in CYP2B6 , such as CYP2B6 * 6 , can alter bupropion metabolism and may affect bupropion treatment outcome . METHODS Subjects participated in a smoking cessation clinical trial of bupropion versus placebo . The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment ( i.e. , end of treatment ) and at the 6-month follow-up ; secondary outcomes were severity of adverse effects , withdrawal , and urge to smoke . Subjects were haplotyped for the CYP2B6 * 6 variants . RESULTS Among smokers in the CYP2B6 * 6 group ( CYP2B6 * 1/*6 or CYP2B6 * 6/*6 genotype , n = 147 , 45 % of the population ) , bupropion produced significantly higher abstinence rates than placebo at the end of treatment ( 32.5 % vs. 14.3 % , p = .01 ) and at the 6-month follow-up ( 31.2 % vs. 12.9 % , p = .008 ) . In contrast , bupropion was no more effective than placebo for smokers in the CYP2B6 * 1 group ( CYP2B6 * 1/*1 , n = 179 ) at the end of treatment ( 31.0 % vs. 31.6 % , p = .93 ) or at the 6-month follow-up ( 22.0 % vs. 21.5 % , p = .94 ) . There was a significant genotype by treatment interaction at the end of treatment ( odds ratio [ OR ] = 2.97 , confidence interval [ CI ] = 1.05 - 8.40 , p = .04 ) , which was similar at 6-month follow-up ( OR = 2.98 , CI = .98 - 9.06 , p = .05 ) . CONCLUSIONS These data suggest that smokers with the CYP2B6 * 6 genotype have a higher liability to relapse on placebo and that they may be good c and i date s for bupropion treatment for smoking cessation Polymorphisms in the dopamine D2 receptor ( DRD2 C/T and DRD2 A/G ) and in dopamine beta hydroxylase ( DBH A/G ) have been implicated in modulation of smoking and other reward-seeking behaviours . We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation . In 1991 - 93 , we performed a r and omized controlled trial of the nicotine patch on 1686 heavy smokers ( > or = 15 cigarettes/day ) . In 1999 - 2000 , we contacted 1532 of the 1612 subjects still available ; 767 ( 50 % ) completed a question naire and gave a blood sample . In the 755 cases in which DNA was successfully genotyped , we examined associations between the polymorphisms in DRD2 and DBH , and smoking cessation . At 1 week , the patch was more effective for smokers with DRD2 CT/TT genotype [ patch/placebo odds ratio ( OR ) 2.8 , 95 % confidence interval ( CI ) 1.7 - 4.6 ] than with CC ( OR 1.4 , 0.9 - 2.1 ; P for difference in ORs 0.04 ) . Smokers with both DRD2 CT/TT and DBH GA/AA genotypes had an OR of 3.6 ( 2.0 - 6.5 ) compared to 1.4 ( 1.0 - 2.1 ) for others ( P = 0.01 ) . At 12 weeks , the ORs for these genotypic groups were 3.6 ( 1.7 - 7.8 ) and 1.4 ( 0.9 - 2.3 ) , respectively ( P = 0.04 ) . There was no association between patch effectiveness and DRD2 exon 8 . Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype . Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype The ability to quit smoking is heritable , yet few genetic studies have investigated prospect i ve smoking cessation . We conducted a systems-based genetic association analysis in a sample of 472 treatment-seeking smokers of European ancestry after 8 weeks of transdermal nicotine therapy for smoking cessation . The genotyping panel included 169 single-nucleotide polymorphisms ( SNPs ) in 7 nicotinic acetylcholine receptor subunit genes and 4 genes in the endogenous cholinergic system . The primary outcome was smoking cessation ( biochemically confirmed ) at the end of treatment . SNPs clustered in the choline acetyltransferase ( ChAT ) gene were individually identified as nominally significant , and a 5-SNP haplotype ( block 6 ) in ChAT was found to be significantly associated with quitting success . Single SNPs in ChAT haplotype block 2 were also associated with pretreatment levels of nicotine dependence in this cohort . To replicate associations of SNPs in haplotype blocks 2 and 6 of ChAT with nicotine dependence in a non-treatment-seeking cohort , we used data from an independent community-based sample of 629 smokers representing 200 families of European ancestry . Significant SNP and haplotype associations were identified for multiple measures of nicotine dependence . Although the effect sizes in both cohorts are modest , converging data across cohorts and phenotypes suggest that ChAT may be involved in nicotine dependence and ability to quit smoking . Additional sequencing and characterization of ChAT may reveal functional variants that contribute to nicotine dependence and smoking cessation AIMS To examine the effectiveness of transdermal selegiline for producing cigarette smoking abstinence . DESIGN Adult smokers were r and omly assigned to receive selegiline transdermal system ( STS ) or placebo given for 8 weeks . All participants received cognitive behavior therapy ( CBT ) . Follow-ups were conducted at 25 and 52 weeks . SETTING Community smoking cessation clinic . PARTICIPANTS 243 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . MEASURES Expired-air carbon monoxide confirmed 7-day point prevalence abstinence . FINDINGS STS was not superior to placebo . More women than men were abstinent at 52 week follow-up ( 28 % vs 16 % , P < 0.05 ) . Behavioral activation ( BAS ) moderated treatment response ( P = 0.01 ) . The survival rate through week 52 for those with high ' drive ' scores on the BAS was 47 % if assigned to selegiline and 34 % if assigned to placebo . The survival rate for those with low ' drive scores ' on the BAS was 35 % if assigned to selegiline compared to 53 % if assigned to placebo . CONCLUSION Transdermal selegiline does not appear generally effective in aiding smoking cessation though there may be a selective effect in those smokers with low ' behavioral activation ' The overall effectiveness of nicotine replacement therapy could be greater if the therapy were targeted at those most likely to respond . Variants of the dopamine D2 receptor ( DRD2 32806 C/T ) have been implicated in the initiation and maintenance of smoking,1 2 and these variants may also be related to response to nicotine replacement therapy.3 Additionally , mechanisms of nicotine addiction may differ in men and women.4 With this evidence in mind , we examined whether the response to nicotine replacement therapy is modified by sex and genotype . A r and omised controlled trial of nicotine patches in 1991 - 2 recruited 1686 heavy smokers ( ≥15 cigarettes a day).5 The participants wore patches for 12 weeks . Abstinence from smoking was confirmed at one week by expired carbon monoxide concentration ≤ 10 ppm , and at 12 , 24 , and 52 weeks by salivary cotinine concentration ≤ 20 ng/ml ( 89 % of cases ) or by expired carbon monoxide concentration ≤10 ppm . In 1999 - 2000 , we contacted 1532 of the 1625 participants still alive ; the mean In this double-blind , placebo-controlled smoking cessation treatment study , 608 participants were r and omly assigned to receive active bupropion and active 4-mg gum ( AA , n = 228 ) , active bupropion and placebo gum ( AP , n = 224 ) , or placebo bupropion and placebo gum ( PP , n = 156 ) . Relative to the PP group , the AA and AP groups were each significantly more likely to be abstinent at 1 week , end of treatment , and 6 months but not at 12 months postquit . After the first week postquit there were no differences in abstinence rates between the AA and AP groups . We found no significant individual difference variables that moderated outcome beyond 1 week postquit In this follow-up of a r and omized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation , 741 smokers of European ancestry who were r and omized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region . The study setting was a primary care research network in Oxfordshire , United Kingdom . The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up . The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment ( SL : p=.33 ; SS : p=.81 ) or 24-week follow-up ( SL : p=.05 ; SS : p=.21 ) , and we found no evidence for a genotypextreatment interaction effect . In summary , despite the theoretically important contribution of serotonin neurotransmission to smoking cessation , the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial Purpose . To examine disparities and changes over time in the population -level distribution of smokers along a cigarette quitting continuum among African American smokers compared with non-Hispanic Whites . Methods . Secondary data analyses of the 1999 , 2002 , 2005 , and 2008 California Tobacco Surveys ( CTS ) . The CTS are large , r and om-digit-dialed , population -based surveys design ed to assess changes in tobacco use in California . The number of survey respondents ranged from n = 6,744 to n = 12,876 across CTS years . Current smoking behavior ( daily or nondaily smoking ) , number of cigarettes smoked per day , intention to quit in the next 6 months , length of most recent quit attempt among current smokers , and total length of time quit among former smokers were assessed and used to recreate the quitting continuum model . Results . While current smoking rates were significantly higher among African Americans compared with non-Hispanic Whites across all years , cigarette consumption rates were lower among African Americans in all years . There were significant increases in the proportion of former smokers who had been quit for at least 12 months from 1999 ( African Americans , 26.8 % ± 5.5 % ; non-Hispanic Whites , 36.8 % ± 1.6 % ) to 2008 ( African Americans , 43.6 % ± 4.1 % ; non-Hispanic Whites , 57.4 % ± 2.9 % ) . The proportion of African American former smokers in each CTS year was significantly lower than that of non-Hispanic Whites . Conclusions . Despite positive progression along the quitting continuum for both African American and non-Hispanic White smokers , the overall distribution was less favorable for African Americans . The lower smoking consumption levels among African Americans , combined with the lower rates of successful smoking cessation , suggest that cigarette addiction and the quitting process may be different for African American smokers AIMS To confirm and extend to primary care setting s prior genome-wide association results that distinguish smokers who successfully quit from individuals who were not able to quit smoking in clinical trials . MATERIAL S & METHODS Affymetrix 6.0 Arrays were used to study DNA from successful quitters and matched individuals who did not quit from the Patch in Practice study of 925 smokers in 26 UK general practice s who were provided with 15 mg/16 h nicotine-replacement therapy and varying degrees of behavioral support . RESULTS Only a few SNPs provided results near ' genome-wide ' levels of significance . Nominally significant ( p < 0.01 ) SNP results identify the same chromosomal regions identified by prior genome-wide association studies to a much greater extent than expected by chance . CONCLUSION Ability to change smoking behavior in a general practice setting appears to share substantial underlying genetics with the ability to change this behavior in clinical trials , though the modest sample sizes available for these studies provides some caution to these conclusions In the current study , we investigated how individual variants in the serotonin promoter gene , previously associated with smoking cessation and linked to anxiety-related personality traits , were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy ( CBT ) in a clinical population . We hypothesize that subjects with the long allele may be less responsive to treatment . Altogether 61 schizophrenic patients ( 46 M , 15 F ) on stable neuroleptic medication were initially enrolled in a smoking reduction program ( prospect i ve , double-blind , placebo-controlled ) including cognitive behavioral therapy plus placebo or CBT plus bupropion . Additionally , subjects were genotyped for a polymorphism in the serotonin transporter ( SLC6A4 ) . Thirty-two subjects ( 23 M , 9 F ) completed a 14-week course of treatment . While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT , subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo . In addition , analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked . Only male subjects with at least one short promoter region allele ( short/short and short/long combined ) showed a reduction in cigarette consumption as a result of treatment . This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy |
522 | 31,465,458 | Sports-specific IPPs have the strongest influence on most performance indices based on the significant improvement versus control groups . | INTRODUCTION Injury prevention programs ( IPPs ) are an inherent part of training in recreational and professional sports .
Providing performance-enhancing benefits in addition to injury prevention may help adjust coaches and athletes ' attitudes towards implementation of injury prevention into daily routine .
Conventional thinking by players and coaches alike seems to suggest that IPPs need to be specific to one 's sport to allow for performance enhancement .
The systematic literature review aims to firstly determine the IPPs nature of exercises and whether they are specific to the sport or based on general conditioning .
Secondly , can they demonstrate whether general , sports-specific or even mixed IPPs improve key performance indicators with the aim to better facilitate long-term implementation of these programs ? | Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Female soccer players are three times more likely to suffer a non-contact anterior cruciate ligament ( ACL ) tear compared with male soccer players . Several ACL injury prevention programs have been developed and are used to reduce injury risk . However , to date there is limited information on how such programs affect physical performance . The aim of this r and omized controlled study was to investigate the effects of the Prevent Injury Enhance Performance ( PEP ) program in adolescent female soccer players . Four soccer teams were r and omly assigned to an intervention ( PEP ) or control ( CON ) group and assessed at baseline , 6 weeks , and 12 weeks on linear sprinting , countermovement jump ( CMJ ) , and two agility tests . A mixed model factorial ANOVA with repeated measures was used to assess for treatment effects on the dependent variables . Improvements in 27.3 and 36.6 m sprint times ( < 0.10 s ) were evident during the first 6 weeks for PEP , but reverted back to baseline values by 12 weeks ; there were no changes for 9.1 or 18.2 m sprint times in either group . There was no change in the CMJ height for PEP ; however , there was a decrement at 6 and 12 weeks compared with baseline in CON . Performance on the Illinois and pro-agility tests declined in both groups . Our findings demonstrate that improvements in linear sprint performance were small and transient in adolescent female soccer players , and that there was no benefit of the PEP program on CMJ or agility performance . ACL injury prevention programs design ed as a structured warm-up routine seem to lack the necessary stimulus to enhance athletic performance Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose The objective of the present r and omised controlled trial was to study the effect of a neuromuscular warm-up programme on performance tests in youth female football . Methods Four youth female football teams with players aged 12–16 years were r and omised into an intervention group and control group . The intervention was a 15-min neuromuscular warm-up programme carried out twice a week during the 11-week study period . Baseline and follow-up measurements of performance were made indoors and included the star excursion balance test , a countermovement jump test , a triple-hop for distance test , a modified Illinois agility test , and 10- and 20-m sprint tests . Results Fifty-two players ( intervention 28 ; control 24 ) took part in baseline measurements , and after dropout , 41 players ( intervention 23 ; control 18 ) were included for analysis . Minor positive changes were seen in the control group compared to the intervention group for a sub-score of the star excursion balance test ( P < 0.05 ) and in the modified Illinois agility test ( P < 0.05 ) . No improvement was seen in the intervention group from baseline to follow-up . Conclusions The study showed that a neuromuscular warm-up programme carried out during 11 weeks did not improve performance in youth female football . This could indicate that the programme does not contain sufficient stimulus to improve performance . A low player attendance at training sessions , and low specificity between exercises in the warm-up programme and the evaluated performance tests may also contribute to the lack of effect . Level of evidence Abstract Ramírez-Campillo , R , Álvarez , C , Henríquez-Olguín , C , Baez , EB , Martínez , C , And rade , DC , and Izquierdo , M. Effects of plyometric training on endurance and explosive strength performance in competitive middle- and long-distance runners . J Strength Cond Res 28(1 ) : 97–104 , 2014—The purpose of this study was to examine the effect of a short-term plyometric training program on explosive strength and endurance performance in highly competitive middle- and long-distance runners . Athletes were r and omly assigned to a control group ( CG , n = 18 , 12 men ) and an explosive strength training group ( TG , n = 18 , 10 men ) . Drop jump ( DJ ) from 20 ( DJ20 ) and 40 cm ( DJ40 ) , countermovement jump with arms ( CMJA ) , 20-m sprint time , and 2.4-km endurance run time test were carried out before and after 6 weeks of explosive strength training . Also , the combined st and ardized performance ( CSP ) in the endurance and explosive strength test was analyzed . After intervention , the CG did not show any significant change in performance , whereas the TG showed a significant reduction in 2.4-km endurance run time ( −3.9 % ) and 20-m sprint time ( −2.3 % ) and an increase in CMJA ( + 8.9 % ) , DJ20 ( + 12.7 % ) , and DJ40 ( 16.7 % ) explosive performance . Strength training group also exhibited a significant increase in CSP , although the CG showed significant reduction . We conclude that properly programmed concurrent explosive strength and endurance training could be advantageous for middle- and long-distance runners in their competitive performance , especially in events characterized by sprinting actions with small time differences at the end of the race Purpose The study investigated the effects of FIFA 11 + and HarmoKnee , both being popular warm-up programs , on proprioception , and on the static and dynamic balance of professional male soccer players . Methods Under 21 year-old soccer players ( n = 36 ) were divided r and omly into 11 + , HarmoKnee and control groups . The programs were performed for 2 months ( 24 sessions ) . Proprioception was measured bilaterally at 30 ° , 45 ° and 60 ° knee flexion using the Biodex Isokinetic Dynamometer . Static and dynamic balances were evaluated using the stork st and test and Star Excursion Balance Test ( SEBT ) , respectively . Results The proprioception error of dominant leg significantly decreased from pre- to post-test by 2.8 % and 1.7 % in the 11 + group at 45 ° and 60 ° knee flexion , compared to 3 % and 2.1 % in the HarmoKnee group . The largest joint positioning error was in the non-dominant leg at 30 ° knee flexion ( mean error value = 5.047 ) , ( p<0.05 ) . The static balance with the eyes opened increased in the 11 + by 10.9 % and in the HarmoKnee by 6.1 % ( p<0.05 ) . The static balance with eyes closed significantly increased in the 11 + by 12.4 % and in the HarmoKnee by 17.6 % . The results indicated that static balance was significantly higher in eyes opened compared to eyes closed ( p = 0.000 ) . Significant improvements in SEBT in the 11 + ( 12.4 % ) and HarmoKnee ( 17.6 % ) groups were also found . Conclusion Both the 11 + and HarmoKnee programs were proven to be useful warm-up protocol s in improving proprioception at 45 ° and 60 ° knee flexion as well as static and dynamic balance in professional male soccer players . Data from this research may be helpful in encouraging coaches or trainers to implement the two warm-up programs in their soccer teams Purpose Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations . Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored . The objective was to determine the time course of neuromuscular training effects on functional , dynamic and static balance measures . Methods Thirty youth ( 14.9 ± 3 years ) field hockey athletes were r and omised to an intervention or control group . The intervention included a 20-min neuromuscular warm-up program performed twice weekly for 10 weeks . Balance assessment s were performed at baseline , week three , week six and post-intervention . They included the star excursion balance test ( SEBT ) , balance error scoring system ( BESS ) , jump-l and ing time to stabilization ( TTS ) and center of pressure ( COP ) sway velocity during single-leg st and ing . Results No baseline differences were found between groups in demographic data and balance measures . Adherence was at 86 % . All balance measures except the medial – lateral TTS improved significantly over time ( p < 0.05 ) in both groups . Significant group by time interactions were found for the BESS score ( p < 0.001 ) . The intervention group showed greater improvements ( 69.3 ± 10.3 % ) after 10 weeks in comparison to controls ( 31.8 ± 22.1 % ) . There were no significant group by time interactions in the SEBT , TTS and COP sway velocity . Conclusions Neuromuscular training was effective in improving postural control in youth team athletes . However , this effect was not reflected in all balance measures suggesting that the neuromuscular training did not influence all dimensions of postural control . Further studies are needed to confirm the potential of specific warm-up programs to improve postural control STUDY DESIGN Controlled cohort repeated- measures experimental design . OBJECTIVES To determine if a neuromuscular training program ( NMTP ) focused on core stability and lower extremity strength would affect performance on the star excursion balance test ( SEBT ) . We hypothesized that NMTP would improve SEBT performance in the experimental group and there would be no side-to-side differences in either group . BACKGROUND The SEBT is a functional screening tool that is used to assess dynamic stability , monitor rehabilitation progress , assess deficits following an injury , and identify athletes at high risk for lower extremity injury . The SEBT requires lower extremity coordination , balance , flexibility , and strength . METHODS Twenty uninjured female soccer players ( 13 experimental , 7 control ) participated . Players trained together as a team , so group allocation was not r and omized . The SEBT was administered prior to and following 8 weeks of NMTP in the experimental group and 8 weeks of no NMTP in the control group . A 3-way mixed-model ANOVA was used to determine the effect of group ( experimental versus control ) , training ( pretraining versus posttraining ) , and limb ( right versus left ) . RESULTS After participation in a NMTP , subjects demonstrated a significant improvement in the SEBT composite score ( mean ± SD ) on the right limb ( pretraining , 96.4 % ± 11.7 % ; posttraining , 104.6 % ± 6.1 % ; P = .03 ) and the left limb ( pretraining , 96.9 % ± 10.1 % ; posttraining , 103.4 % ± 8.0 % ; P = .04 ) . The control group had no change on the SEBT composite score for the right ( pretraining , 95.7 % ± 5.2 % ; posttraining , 94.4 % ± 5.2 % ; P = .15 ) or the left ( 97.4 % ± 7.2 % ; 93.6 % ± 5.0 % ; P = .09 ) limb . Further analysis identified significant improvement for the SEBT in the posterolateral direction on both the right ( P = .008 ) and left ( P = .040 ) limb and the posteromedial direction of the left limb ( P = .028 ) in the experimental group . CONCLUSION Female soccer players demonstrated an improved performance on the SEBT after NMTP that focused on core stability and lower extremity strength Objective To examine the effect of a comprehensive warm-up programme design ed to reduce the risk of injuries in female youth football . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 125 football clubs from the south , east , and middle of Norway ( 65 clusters in the intervention group ; 60 in the control group ) followed for one league season ( eight months ) . Participants 1892 female players aged 13 - 17 ( 1055 players in the intervention group ; 837 players in the control group ) . Intervention A comprehensive warm-up programme to improve strength , awareness , and neuromuscular control during static and dynamic movements . Main outcome measure Injuries to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . Results During one season , 264 players had relevant injuries : 121 players in the intervention group and 143 in the control group ( rate ratio 0.71 , 95 % confidence interval 0.49 to 1.03 ) . In the intervention group there was a significantly lower risk of injuries overall ( 0.68 , 0.48 to 0.98 ) , overuse injuries ( 0.47 , 0.26 to 0.85 ) , and severe injuries ( 0.55 , 0.36 to 0.83 ) . Conclusion Though the primary outcome of reduction in lower extremity injury did not reach significance , the risk of severe injuries , overuse injuries , and injuries overall was reduced . This indicates that a structured warm-up programme can prevent injuries in young female football players . Trial registration IS RCT N10306290 Chelly , MS , Ghenem , MA , Abid , K , Hermassi , S , Tabka , Z , and Shephard , RJ . Effects of in-season short-term plyometric training program on leg power , jump- and sprint performance of soccer players . J Strength Cond Res 24(10 ) : 2670 - 2676 , 2010-Our hypothesis was that the addition of an 8-week lower limb plyometric training program ( hurdle and depth jumping ) to normal in-season conditioning would enhance measures of competitive potential ( peak power output [ PP ] , jump force , jump height , and lower limb muscle volume ) in junior soccer players . The subjects ( 23 men , age 19 ± 0.7 years , body mass 70.5 ± 4.7 kg , height 1.75 ± 0.06 m , body fat 14.7 ± 2.6 % ) were r and omly assigned to a control ( normal training ) group ( Gc ; n = 11 ) and an experimental group ( Gex , n = 12 ) that also performed biweekly plyometric training . A force-velocity ergometer test determined PP . Characteristics of the squat jump ( SJ ) and the countermovement jump ( CMJ ) ( jump height , maximal force and velocity before take-off , and average power ) were determined by force platform . Video-camera kinematic analyses over a 40-m sprint yielded running velocities for the first step ( VS ) , the first 5 m ( V5 m ) and between 35 and 40 m ( Vmax ) . Leg muscle volume was estimated using a st and ard anthropometric kit . Gex showed gains relative to controls in PP ( p < 0.01 ) ; SJ ( height p < 0.01 ; velocity p < 0.001 ) , CMJ ( height p < 0.001 ; velocity p < 0.001 , average power p < 0.01 ) and all sprint velocities ( p < 0.001 for V5 m and Vmax , p < 0.01 for VS ) . There was also a significant increase ( p < 0.05 ) in thigh muscle volume , but leg muscle volume and mean thigh cross-sectional area remain unchanged . We conclude that biweekly plyometric training of junior soccer players ( including adapted hurdle and depth jumps ) improved important components of athletic performance relative to st and ard in-season training . Accordingly , such exercises are highly recommended as part of an annual soccer training program Background : Muscle injuries constitute a large percentage of all injuries in football . Purpose : To investigate the incidence and nature of muscle injuries in male professional footballers . Study Design : Cohort study ; Level of evidence , 2 . Methods : Fifty-one football teams , comprising 2299 players , were followed prospect ively during the years 2001 to 2009 . Team medical staff recorded individual player exposure and time-loss injuries . The first-team squads of 24 clubs selected by the Union of European Football Associations as belonging to the best European teams , 15 teams of the Swedish First League , and another 15 European teams playing their home matches on artificial turf pitches were included . A muscle injury was defined as “ a traumatic distraction or overuse injury to the muscle leading to a player being unable to fully participate in training or match play . ” Results : In total , 2908 muscle injuries were registered . On average , a player sustained 0.6 muscle injuries per season . A squad of 25 players can thus expect about 15 muscle injuries per season . Muscle injuries constituted 31 % of all injuries and caused 27 % of the total injury absence . Ninety-two percent of all muscle injuries affected the 4 major muscle groups of the lower limbs : hamstrings ( 37 % ) , adductors ( 23 % ) , quadriceps ( 19 % ) , and calf muscles ( 13 % ) . Sixteen percent of the muscle injuries were reinjuries . These reinjuries caused significantly longer absences than did index injuries . The incidence of muscle injury increased with age . When separated into different muscle groups , however , an increased incidence with age was found only for calf muscle injuries and not for hamstring , quadriceps , or hip/groin strains . Conclusion : Muscle injuries are a substantial problem for players and their clubs . They constitute almost one third of all time-loss injuries in men ’s professional football , and 92 % of all injuries affect the 4 big muscle groups in the lower limbs The injury rate in football is high , and effective injury prevention methods are needed . An exercise program , the " 11 , " has been design ed to prevent the most common injury types in football . However , the effect of such a program on performance is not known . The aim of this r and omized-controlled trial was to investigate the effect of the " 11 " on performance after a 10-week training period . Thirty-four adolescent female football players were r and omly assigned to either an intervention ( n=18 ) or a control group ( n=16 ) . The " 11 " is a 15-min program consisting of ten exercises for core stability , lower extremity strength , balance and agility . Performance tests included isokinetic and isometric strength protocol s for the quadriceps and hamstrings , isometric hip adduction and abduction strength , vertical jump tests , sprint running and soccer skill tests . There was no difference between the intervention and control groups in the change in performance from the pre- to post-test for any of the tests used . In conclusion , no effect was observed on a series of performance tests in a group of adolescent female football players using the " 11 " as a structured warm-up program A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low Abstract Ramos Veliz , R , Requena , B , Suarez-Arrones , L , Newton , RU , and Sáez de Villarreal , E. Effects of 18-week in-season heavy-resistance and power training on throwing velocity , strength , jumping , and maximal sprint swim performance of elite male water polo players . J Strength Cond Res 28(4 ) : 1007–1014 , 2014—We examined the effects of 18 weeks of strength and high-intensity training on key sport performance measures of elite male water polo ( WP ) players . Twenty-seven players were r and omly assigned to 2 groups , control ( in-water training only ) and strength group , ( strength training sessions [ twice per week ] + in-water training ) . In-water training was conducted 5 d·wk−1 . Twenty-meter maximal sprint swim , maximal dynamic strength 1-repetition maximum ( 1RM ) for upper bench press ( BP ) and lower full squat ( FS ) body , countermovement jump ( CMJ ) , and throwing velocity were measured before and after the training . The training program included upper and lower body strength and high-intensity exercises ( BP , FS , military press , pull-ups , CMJ loaded , and abs ) . Baseline-training results showed no significant differences between the groups in any of the variables tested . No improvement was found in the control group ; however , meaningful improvement was found in all variables in the experimental group : CMJ ( 2.38 cm , 6.9 % , effect size [ ES ] = 0.48 ) , BP ( 9.06 kg , 10.53 % , ES = 0.66 ) , FS ( 11.06 kg , 14.21 % , ES = 0.67 ) , throwing velocity ( 1.76 km·h−1 , 2.76 % , ES = 0.25 ) , and 20-m maximal sprint swim ( −0.26 seconds , 2.25 % , ES = 0.29 ) . Specific strength and high-intensity training in male WP players for 18 weeks produced a positive effect on performance qualities highly specific to WP . Therefore , we propose modifications to the current training methodology for WP players to include strength and high-intensity training for athlete preparation in this sport Abstract Hoshikawa , Y , Iida T , Muramatsu , M , Ii , N , Nakajima , Y , Chumank , K , and Kanehisa , H. Effects of stabilization training on trunk muscularity and physical performances in youth soccer players . J Strength Cond Res 27(11 ) : 3142–3149 , 2013—The purpose of the present study was to examine the effects of stabilization training on trunk muscularity and physical performances in youth male soccer players aged 12–13 yrs ( n = 28 ) . The subjects allocated to training ( TG , n = 16 ) performed a stabilization exercise program consisting of 5 exercises ( elbow – toe , elbow – heel , side bridge , modified 1-legged squat , and bent-knee push-up ) 4 times per week and a training program specific to soccer 6 times per week , whereas the others ( control , n = 12 ) conducted the soccer training only for 6 months . Before and after the intervention , the cross-sectional areas ( CSAs ) of 5 muscles ( rectus abdominus , oblique , psoas major , quadratus lumborum , and erector spinae ) were determined using magnetic resonance imaging . Furthermore , peak torques during hip extension and flexion at 1.05 rad/second , heights of squat and countermovement jumps , and time taken to sprint 15 m were also measured . After 6 months , both groups significantly increased the CSAs of the 5 muscle groups ( TG : 4.4–13.4 % , control : 5.5–10.9 % ) and improved sprint time ( TG : −1.4 % , control : −1.6 % ) , without significant effect of group , but only TG significantly increased the heights of squat ( 5.0 % ) and countermovement ( 6.8 % ) jumps . In addition , a greater increase in hip extension torque was found in TG ( 40.8 % ) than in control ( 17.4 % ) . The current results indicate that , at least in early adolescent soccer players , adding stabilization exercise to soccer training can not increase the trunk muscularity , but it will improve hip extensor strength and vertical jump performance OBJECTIVES To examine rates of sport participation , sport injury , risk factors and sport safety practice s in young adolescents . DESIGN Cross-sectional . SETTING Calgary and area junior high schools . PARTICIPANTS A r and om sample of 1466 students ( aged 12 to 15 years ) . OUTCOME MEASURES Sport injury within one year prior to completing the survey . RESULTS Ninety-three per cent of students participated in sports in the previous year . The injury rate was 60.85 injuries/100 students/year ( 95 % CI 58.29 to 63.35 ) for students reporting at least one sport injury , 29.4 injuries/100 students/year ( 95 % CI 27.08 to 31.81 ) for medically treated injuries , and 12.28 injuries/100 students/year ( 95 % CI 10.64 to 14.07 ) for injuries presenting to a hospital emergency department . The greatest proportion of injuries occurred in basketball ( 14 % ) , soccer ( 12 % ) , hockey ( 8.6 % ) and snowboarding/skiing ( 7.1 % ) . CONCLUSIONS The rates of participation and injury in sports are high in junior high school students . Future research should focus on prevention strategies in sports with high participation and injury rates to have the greatest population health impact Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Abstract Hermassi , S , van den Tillaar , R , Khlifa , R , Chelly , MS , and Chamari , K. Comparison of in-season-specific resistance vs. a regular throwing training program on throwing velocity , anthropometry , and power performance in elite h and ball players . J Strength Cond Res 29(8 ) : 2105–2114 , 2015—The purpose of this study was to compare the effect of a specific resistance training program ( throwing movement with a medicine ball ) with that of regular training ( throwing with regular balls ) on ball velocity , anthropometry , maximal upper-body strength , and power . Thirty-four elite male team h and ball players ( age : 18 ± 0.5 years , body mass : 80.6 ± 5.5 kg , height : 1.80 ± 5.1 m , body fat : 13.4 ± 0.6 % ) were r and omly assigned to 1 of the 3 groups : control ( n = 10 ) , resistance training group ( n = 12 ) , or regular throwing training group ( n = 12 ) . Over the 8-week in season , the athletes performed 3 times per week according to an assigned training program alongside their normal team h and ball training . One repetition maximum ( 1RM ) bench press and 1RM pullover scores assessed maximal arm strength . Anthropometry was assessed by body mass , fat percentage , and muscle volumes of upper body . H and ball throwing velocity was measured by a st and ing throw , a throw with run , and a jump throw . Power was measured by measuring total distance thrown by a 3-kg medicine ball overhead throw . Throwing ball velocity , maximal strength , power , and muscle volume increases for the specific resistance training group after the 8 weeks of training , whereas only maximal strength , muscle volume and power and in the jump throw increases were found for the regular throwing training group . No significant changes for the control group were found . The current findings suggest that elite male h and ball players can improve ball velocity , anthropometrics , maximal upper-body strength , and power during the competition season by implementing a medicine ball throwing program |
523 | 31,608,981 | Our synthesis showed that clients ' experiences of these types of programmes were mixed .
However , clients also pointed to problems when using these programmes .
The cost of messages could also be a problem , and many thought that messages should be free of charge ( high confidence ) .
Language issues as well as skills in reading , writing , and using mobile phones could also be a problem ( moderate confidence ) .
Clients dealing with stigmatised or personal health conditions such as HIV , family planning , or abortion care were also concerned about privacy and confidentiality ( high confidence ) .
Some clients suggested strategies to deal with these issues , such as using neutral language and tailoring the content , timing , and frequency of messages ( high confidence ) .
Clients wanted messages at a time and frequency that was convenient for them ( moderate confidence ) .
Clients ' views about who sent the digital health communication could influence their views of the programme ( moderate confidence ) .
Our matrix shows that many of the trials assessing these types of programmes did not try to address the problems we identified , although this may have been a reporting issue .
Authors ' conclusions Our synthesis identified several factors that can influence the successful implementation of targeted client communication programmes using mobile devices . | Abstract Background Governments and health systems are increasingly using mobile devices to communicate with patients and the public .
Targeted digital client communication is when the health system transmits information to particular individuals or groups of people , based on their health or demographic status .
Common types of targeted client communication are text messages that remind people to go to appointments or take their medicines .
Other types include phone calls , interactive voice response , or multimedia messages that offer healthcare information , advice , monitoring , and support .
Objectives To explore clients ' perceptions and experiences of targeted digital communication via mobile devices on topics related to reproductive , maternal , newborn , child , or adolescent health ( RMNCAH ) . | Background Undernutrition is a major concern for Myanmar children with low exclusive breastfeeding rate ( 24 % ) . A formative study was conducted to explore the perceptions and practice s relating to exclusive breastfeeding , and barriers and facilitators to using mobile communications for exclusive breastfeeding counselling . The results inform the design of a r and omized control trial to promote exclusive breastfeeding practice s among Myanmar mothers . Methods We conducted twenty in-depth interviews with pregnant women and accompanying family members attending an antenatal clinic at the Central Women ’s Hospital , Yangon , seven key-informant interviews and one focus group discussion with fifteen service providers such as nurses , doctors , managers and staff from the National Nutrition Centre , Department of Health , United Nations Children ’s Fund International and National Non-Government Organizations and Ooredoo , a private mobile company . Results Widespread practice s of feeding water , honey , infant formula and semi-solid food were reported to be existed in the community before the child reaches four months , mostly influenced by gr and mothers from both sides . All couples knew breast milk was good for baby and intended to breastfeed , though limited underst and ing of the term exclusive breastfeeding was reported . Perception that breast milk alone was not sufficient to provide all nutrients needed for the first six months of baby ’s life , mother had insufficient milk supply or breast problems , mother ’s back to work and gr and mothers ’ influence emerged as barriers to breastfeed exclusively for six months . All women knew how to make basic phone calls , majority could read mobile text message in Burmese and possess mobile phones while a few of them shared phones with their husb and s. All couples preferred to receive text messages 2–3 times per week in the evening . Institutional staff suggested messages to be simple , easily underst and able and culturally appropriate . Perceived barriers included limited mobile network coverage , affordability of mobile h and set and phone bills , literacy and community familiarity with text messages . All respondents welcomed the idea of planned intervention . Conclusion We incorporated findings to develop messages and determine the modality , inclusion criteria and tailored with gestation and child age , to be delivered in the r and omized controlled trial intervention This r and omized behavioral trial examined whether youth living with HIV ( YLH ) receiving cell-phone support with study funded phone plans , demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls . Monday through Friday phone calls confirmed medications were taken , provided problem-solving support , and referred to services to address adherence barriers . Of 37 participants ( ages 15–24 ) , 62 % were male and 70 % were African American . Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month ( P = 0.007 ) and log 10 HIV VL was significantly lower at both 24 weeks ( 2.82 versus 4.52 P = 0.002 ) and 48 weeks ( 3.23 versus 4.23 P = 0.043 ) . Adherence and viral load showed medium to large effect sizes across the 48 week study . This is the first study to demonstrate sustained clinical ly significant reductions in HIV VL using youth friendly technology . ResumenEste ensayo de comportamiento aleatorio examinó si los jóvenes que viven con el VIH ( YLH ) reciben apoyo por celular con el estudio financiado de teléfono , se demostró un mejor cumplimiento y control viral durante la intervención de 24 semanas y 24 semanas después de la intervención en comparación con los controles . De Lunes a Viernes las llamadas telefónicas confirmaron los medicamentos , apoyaron la resolución de problemas , y se refirió a los servicios para hacer frente a las barreras de adherencia . De los 37 participantes ( siglos 15–24 ) , el 62 % eran hombres y el 70 % eran afroamericanos . Adherencia auto-reportada fue significativamente mayor en el grupo de intervención en comparación con el control a las 24 y 48 semanas del mes pasado ( P = 0.007 ) y el log 10 VL VIH fue significativamente menor en ambos 24 semanas ( 2.82 versus 4.52 P = 0.002 ) y 48 semanas ( 3.23 versus 4.23 P = 0.043 ) . La adhesión y la carga viral mostraron medianas y gr and es tamaños del efecto en todo el estudio de 48 semanas . Este es el primer estudio que demuestra descensos importantes de la VL VIH utiliz and o tecnología amigable para la juventud HIV-positive adolescents and young adults often experience suboptimal medication adherence , yet few interventions to improve adherence in this group have shown evidence of efficacy . We conducted a r and omized trial of a two-way , personalized daily text messaging intervention to improve adherence to antiretroviral therapy ( ART ) among N = 105 poorly adherent HIV-positive adolescents and young adults , ages 16–29 . Adherence to ART was assessed via self-reported visual analogue scale ( VAS ; 0–100 % ) at 3 and 6-months for mean adherence level and proportion ≥90 % adherent . The average effect estimate over the 6-month intervention period was significant for ≥90 % adherence ( OR = 2.12 , 95 % CI 1.01–4.45 , p < .05 ) and maintained at 12-months ( 6 months post-intervention ) . Satisfaction scores for the intervention were very high . These results suggest both feasibility and initial efficacy of this approach . Given study limitations , additional testing of this intervention as part of a larger clinical trial with objective and /or clinical outcome measures of adherence is warranted Social media technologies have become increasingly useful tools for research -based interventions . However , participants and social media users have expressed ethical concerns with these studies , such as risks and benefits of participation , as well as privacy , confidentiality , and informed consent issues . This study was design ed to follow up with and assess experiences and perceptions of ethics-related issues among a sample of 211 men who have sex with men who participated in the Harnessing Online Peer Education ( HOPE ) Peru study , a r and omized controlled HIV prevention intervention conducted in Peru . We found that after adjusting for age , highest educational attainment , race , sexual orientation , and prior HIV research experience , participants in the intervention group were more likely than those in the control group to have safe sex ( p = 0.0051 ) and get tested for HIV regularly ( p = 0.0051 ) . As a result of their participation , those in the intervention group benefited more positively than participants in the control group in improving HIV care ( p = 0.0077 ) and learning where to receive sexual health services ( p = 0.0021 ) . Participants in the intervention group expressed higher levels of comfort than those in the control group in joining and seeing other people in the Facebook group ( p = 0.039 ) , seeing other people ’s posts ( p = 0.038 ) and having other group members talk to them online ( p = 0.040 ) . We discuss the implication s of these results as they relate to social media-based HIV research Background Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV . Although different adherence-supporting interventions have been reported , their long term feasibility in low income setting s remains uncertain . Thus , there is a need to explore sustainable context ual adherence aids in such setting s , and to test these using rigorous scientific design s. The current ubiquity of mobile phones in many re source -constrained setting s , make it a context ually appropriate and relatively low cost means of supporting adherence . In India , mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications . This paper presents the study protocol for a trial , to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India . Methods / Design 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India . Patients will be r and omized into control and intervention arms . The control arm will receive the st and ard of care ; the intervention arm will receive the st and ard of care plus mobile phone reminders . Each reminder will take the form of an automated call and a picture message . Reminders will be delivered once a week , at a time chosen by the patient . Patients will be followed up for 24 months or till the primary outcome i.e. virological failure , is reached , whichever is earlier . Self-reported adherence is a secondary outcome . Analysis is by intention-to-treat . A cost-effectiveness study of the intervention will also be carried out . Discussion Stepping up telecommunications technology in re source -limited healthcare setting s is a priority of the World Health Organization . The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line antiretrovirals in an Indian context .Trial Registration Trial registration : IS RCT N79261738 Background Despite the increasing breast cancer incidence and mortality rates , Korean American immigrant women have one of the lowest rates of breast cancer screening across racial groups in the United States . Mobile health ( mHealth ) , defined as the delivery of health care information or services through mobile communication devices , has been utilized to successfully improve a variety of health outcomes . Objective This study adapted the principles of mHealth to advance breast cancer prevention efforts among Korean American immigrant women , an underserved community . Methods Using a r and omized controlled trial design , 120 Korean American women aged 40 to 77 years were recruited and r and omly assigned to either the mMammogram intervention group ( n=60 ) to receive culturally and personally tailored multilevel and multimedia messages through a mobile phone app along with health navigator services or the usual care control group ( n=60 ) to receive a printed brochure . Outcome measures included knowledge , attitudes , and beliefs about breast cancer screening , readiness for mammography , and mammogram receipt . The feasibility and acceptability of the mMammogram intervention was also assessed . Results The intervention group showed significantly greater change on scores of knowledge of breast cancer and screening guidelines ( P=.01 ) . The intervention group also showed significantly greater readiness for mammography use after the intervention compared with the control group . A significantly higher proportion of women who received the mMammogram intervention ( 75 % , 45/60 ) completed mammograms by the 6-month follow-up compared with the control group ( 30 % , 18/60 ; P<.001 ) . In addition , the intervention group rated satisfaction with the intervention ( P=.003 ) , effectiveness of the intervention ( P<.001 ) , and increase of knowledge on breast cancer and screenings ( P=.001 ) significantly higher than the control group . Conclusions A mobile phone app – based intervention combined with health navigator service was a feasible , acceptable , and effective intervention mechanism to promote breast cancer screening in Korean American immigrant women . A flexible , easily tailored approach that relies on recent technological advancements can reach underserved and hard-to-recruit population s that bear disproportionate cancer burdens . Trial Registration Clinical trials.gov NCT01972048 ; https:// clinical trials.gov/show/NCT01972048 ( Archived by WebCite at https:// clinical trials.gov/archive/NCT01972048/2013_10_29 & NA ; Patient engagement in care and adherence to medication are critical to achieving the full benefits of antiretroviral therapy ( ART ) among people with HIV infection . A r and omized controlled trial in Kenya , WelTelKenya1 , showed that an interactive mobile phone text‐messaging intervention can improve adherence and viral load suppression . We conducted a pilot study to adapt the WelTel intervention for HIV‐infected clients ( n = 25 ) at an HIV clinic in Vancouver , British Columbia . Between April and June 2012 , we recruited five participants from five groups : youth ( 14–24 years ) , mature ( ≥50 years ) , English as a second language , remote ( ≥3 hours travel time to clinic ) , and nonsuppressed ( CD4 + T cell count < 200 cells/mm3 and viral load ≥250 copies/mL on two consecutive occasions ) . Participants described the intervention as a useful way to communicate with health care providers , thus increasing the ability to access services , report side effects , and attend appointments BACKGROUND Oral contraceptive ( OC ) knowledge deficits may contribute to OC discontinuation . We examined the effect of an innovative educational intervention on young women 's OC knowledge . STUDY DESIGN As part of a r and omized trial evaluating the impact of text message reminders on OC continuation , we assessed OC knowledge in 659 women ages 13 - 25 years . Women received routine care or routine care plus 6 months of daily educational text messages . We administered a comprehensive 41-item OC knowledge survey at baseline and 6 months . RESULTS Mean OC knowledge scores improved over time for all women ( baseline 22.8 , 56 % correct versus 24.7 , 60 % at 6 months ) , including knowledge of OC 's mechanisms of action ( p=.004 ) , effectiveness ( p<.001 ) , side effects ( p=.03 ) and benefits ( p<.001 ) . Mean 6-month scores were greater in the intervention ( 25.5 ) than the control group (23.7)(p<.001 ) . In multivariable linear regression models , the text message intervention most strongly predicted OC knowledge ( β=1.6 , 95 % confidence interval 0.9 - 2.2 ) . CONCLUSION Daily educational text messages can modestly improve knowledge of OCs , which may promote successful contraceptive outcomes Background Using social networking websites to recruit research participants is increasingly documented in the literature , although few studies have leveraged these sites to reach those younger than 18 years . Objective To discuss the development and refinement of a recruitment protocol to reach and engage adolescent gay , bisexual , and other teenaged men who have sex with men ( AGBM ) . Participants were recruited for development and evaluation activities related to Guy2Guy , a text messaging – based human immunodeficiency virus infection prevention program . Methods Eligibility criteria included being between 14 to 18 years old ; being a cisgender male ; self-identifying as gay , bisexual , and /or queer ; being literate in English , exclusively owning a cell phone , enrolled in an unlimited text messaging plan , intending to keep their current phone number over the next 6 months , and having used text messaging for at least the past 6 months . Recruitment experiences and subsequent steps to refine the Internet-based recruitment strategy are discussed for 4 research activities : online focus groups , content advisory team , beta test , and r and omized controlled trial ( RCT ) . Recruitment relied primarily on Facebook advertising . To a lesser extent , Google AdWords and promotion through partner organizations working with AGBM youth were also utilized . Results Facebook advertising strategies were regularly adjusted based on preidentified recruitment targets for race , ethnicity , urban-rural residence , and sexual experience . The result was a diverse sample of participants , of whom 30 % belonged to a racial minority and 20 % were Hispanic . Facebook advertising was the most cost-effective method , and it was also able to reach diverse recruitment goals : recruitment for the first focus group cost an average of US $ 2.50 per enrolled participant , and it took 9 days to enroll 40 participants ; the second focus group cost an average of US $ 6.96 per enrolled participant , and it took 11 days to enroll 40 participants . Recruitment for the first content advisory team cost an average of US $ 32.52 per enrolled participant ; the second cost US $ 29.52 per participant . Both recruitment drives required 10 days to enroll 24 participants . For the beta test , recruitment cost an average of US $ 17.19 per enrolled participant , and it took 16 days to complete enrollment of 20 participants . For the RCT , recruitment cost an average of US $ 12.54 per enrolled participant , and it took 148 days to enroll 302 participants . Google AdWords campaigns did not result in any enrolled participants of whom the research staff members were aware . Conclusions Internet-based strategies can be a cost-efficient means to recruit and retain hard-to-reach population s from across the country . With real-time monitoring of participant demographic characteristics , diverse sample s can be achieved . Although Facebook advertising was particularly successful in this study , alternative social media strategies can be explored in future research as these media are ever-changing Background The objectives are to compare the effectiveness of cell phone-supported SMS messaging to st and ard care on adherence , quality of life , retention , and mortality in a population receiving antiretroviral therapy ( ART ) in Nairobi , Kenya . Methods and Design A multi-site r and omized controlled open-label trial . A central r and omization centre provided opaque envelopes to allocate treatments . Patients initiating ART at three comprehensive care clinics in Kenya will be r and omized to receive either a structured weekly SMS ( ' short message system ' or text message ) slogan ( the intervention ) or current st and ard of care support mechanisms alone ( the control ) . Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes . Participants are evaluated at baseline , and then at six and twelve months after initiating ART . The care providers keep a weekly study log of all phone based communications with study participants . Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up . Secondary outcomes are improvements in health , quality of life , social and economic factors , and retention on ART . Primary analysis is by ' intention-to-treat ' . Sensitivity analysis will be used to assess per- protocol effects . Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes . Discussion This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a re source -limited setting .Trial Registration Trial Registration Number : Background Internet-based Smoking Cessation Interventions ( ISCIs ) may help pregnant smokers who are unable , or unwilling , to access face-to-face stop smoking support . Targeting ISCIs to specific groups of smokers could increase their uptake and effectiveness . The current study explored the needs and preferences of pregnant women seeking online stop smoking support with an aim to identify features and components of ISCIs that might be most attractive to this population . Methods We conducted qualitative interviews with thirteen pregnant women who completed the intervention arm of a pilot r and omized controlled trial of a novel ISCI for pregnant smokers ( ‘ MumsQuit ’ ) . The interviews explored women ’s views towards MumsQuit and online support with quitting smoking in general , as well as their suggestions for how ISCIs could be best targeted to pregnancy . Interview transcripts were analyzed using Framework Analysis . Results Participants expressed preferences for an accessible , highly engaging and targeted to pregnancy smoking cessation website , tailored to individuals ’ circumstances as well as use of cessation medication , offering comprehensive and novel information on smoking and quitting smoking in pregnancy , ongoing support with cravings management , as well as additional support following relapse to smoking . Participants also viewed as important targeting of the feedback and progress reports to baby ’s health and development , offering personal support from experts , and providing a discussion forum allowing for communication with other pregnant women wanting to quit . Conclusions The present study has identified a number of potential building blocks for ISCIs targeted to quitting smoking in pregnancy . Pregnant smokers willing to try using ISCI may particularly value an engaging intervention offering a high degree of targeting of comprehensive information to them as a group and tailoring support and advice to their individual needs , as well as one providing post-relapse support , peer-to-peer communication and personal support from experts Background Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality . However , childhood vaccination coverage remains sub-optimal in many setting s. While communication is a key feature of vaccination programmes , we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage . Developing a classification system ( taxonomy ) organised into conceptually similar categories will aid in : underst and ing the relationships between different types of communication interventions ; facilitating conceptual mapping of these interventions ; clarifying the key purpose s and features of interventions to aid implementation and evaluation ; and identifying areas where evidence is strong and where there are gaps . This paper reports on the development of the ‘ Communicate to vaccinate ’ taxonomy . Methods The taxonomy was developed in two stages . Stage 1 included : 1 ) forming an advisory group ; 2 ) search ing for descriptions of interventions in trials ( CENTRAL data base ) and general health literature ( Medline ) ; 3 ) developing a sampling strategy ; 4 ) screening the search results ; 5 ) developing a data extraction form ; and 6 ) extracting intervention data . Stage 2 included : 1 ) grouping the interventions according to purpose ; 2 ) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback ; 3 ) conducting a targeted search of grey literature to supplement the taxonomy ; 4 ) finalising the taxonomy based on the input provided . Results The taxonomy includes seven main categories of communication interventions : inform or educate , remind or recall , teach skills , provide support , facilitate decision making , enable communication and enhance community ownership . These categories are broken down into 43 intervention types across three target groups : parents or soon-to-be-parents ; communities , community members or volunteers ; and health care providers . Conclusions Our taxonomy illuminates and organises this field and identifies the range of available communication interventions to increase routine childhood vaccination uptake . We have utilised a variety of data sources , capturing information from rigorous evaluations such as r and omised trials as well as experiences and knowledge of practitioners and vaccination stakeholders . The taxonomy reflects current public health practice and can guide the future development of vaccination programmes Cervical cancer screening in Malaysia is by opportunistic Pap smear which contributes to the low uptake rate . To overcome this , a pilot project called the SIPPS program ( translated as information system of Pap smear program ) had been introduced whereby women aged 20 - 65 years old are invited for Pap smear and receive recall to repeat the test . This study aim ed at determining which recall method is most cost-effective in getting women to repeat Pap smear . A r and omised control trial was conducted where one thous and women were recalled for repeat smear either by registered letter , phone messages , phone call or the usual postal letter . The total cost applied for cost-effectiveness analysis includes the cost of sending letter for first invitation , cost of the recall method and cost of two Pap smears . Cost-effective analysis ( CEA ) of Pap smear uptake by each recall method was then performed . The uptake of Pap smear by postal letter , registered letters , SMS and phone calls were 18.8 % , 20.0 % , 21.6 % and 34.4 % , respectively ( p<0.05 ) . The CER for the recall method was lowest by phone call compared to other interventions ; RM 69.18 ( SD RM 0.14 ) compared to RM 106.53 ( SD RM 0.13 ) , RM 134.02 ( SD RM 0.15 ) and RM 136.38 ( SD RM 0.11 ) for SMS , registered letter and letter , respectively . ICER showed that it is most cost saving if the usual method of recall by postal letter be changed to recall by phone call . The possibility of letter as a recall for repeat Pap smear to reach the women is higher compared to sending SMS or making phone call . However , getting women to do repeat Pap smear is better with phone call which allows direct communication . Despite the high cost of the phone call as a recall method for repeat Pap smear , it is the most cost-effective method compared to others OBJECTIVE To evaluate if text message reminders increase the likelihood of receiving the influenza vaccine among pregnant women . METHODS Pregnant women were r and omized to either receive or not receive weekly text messages . Women were told the messages would be about health-related behavior in pregnancy . Those r and omized to the intervention group received two messages weekly for four consecutive weeks reinforcing that the influenza vaccine is recommended for all pregnant women and safe during pregnancy and breastfeeding . Women were contacted six weeks postpartum to determine if they had received the vaccine . Sample size calculation determined that 108 women were required in both groups to see a 75 % increase in vaccination rates over baseline in the text message group compared to the control group . RESULTS Recruitment began November 4 , 2013 , and 317 women were r and omized . The mean gestational age at recruitment was 22weeks . There were 40/129 ( 31 % ) women in the text message group and 41/152 ( 27 % ) women in the control group who received the vaccine ( p=0.51 ) . Significant predictors of vaccine acceptance were being married compared to single ( 95 % vs. 67 % , p<0.001 ) , having higher household income ( 55 % vs. 39 % , p=0.03 ) and having received the vaccine before ( 77 % vs. 36 % , p<0.001 ) . Among women receiving text messages , the majority were satisfied , with only 15/129 ( 12 % ) reporting that they did not like receiving the messages , and 24/129 ( 19 % ) stating that the information in the messages was not helpful . CONCLUSION Weekly text messages reinforcing the recommendation for and safety of the influenza vaccine in pregnancy did not increase the likelihood of actually receiving the vaccine among pregnant women . Overall vaccination rates were low , highlighting the need for patient education and innovative techniques to improve vaccine acceptance . Registered with Clinical Trials.gov at http://www . clinical trials.gov , registration number NCT 02428738 Background : HIV and AIDS are major public health problems in the world and Africa . In Cameroon , the HIV prevalence is 5.1 % . Cellphones have been found to be useful in the provision of modern health care services using short message services ( SMS ) . This study assessed the effectiveness of SMS in improving the adherence of people living with HIV and AIDS to their treatment and care in Cameroon . Methods : This intervention study used a r and omized controlled trial design . Ninety participants seeking treatment at the Nkwen Baptist Health Center were recruited between August and September 2011 using a purposive sampling method . They were r and omly allocated into the intervention and control groups , each containing 45 participants . In the intervention group , each participant received four SMSs per week at equal intervals for four weeks . The patients were investigated for adherence to ARVs by evaluating the number of times treatment and medication refill appointments were missed . Data were collected using an interviewer-administered question naire before and after intervention and analysed on STATA . Results : The baseline survey indicated that there were 55(61.1 % ) females and 35(38.9 % ) males aged 23 - 62 years ; the mean age was 38.77 ± 1.08 . Most participants were teachers [ 12 ( 13.3 % ) ] , farmers [ 11 ( 12.2 % ) ] , and businessmen [ 24 ( 26.7 % ) ] . Adherence to ARVs was 64.4 % in the intervention group and 44.2 % in the control group ( p = 0.05 ) . 2(4.4 % ) patients in the control group failed to respect their drug refill appointments while all the 45(100 % ) participants in the intervention group respected their drug refill appointments . 54.17 % of married people and 42.9 % of the participants with primary and secondary levels of education missed their treatment . Key reasons for missing treatment were late home coming ( 54 % ) , forgetfulness ( 22.5 % ) , and travelling out of station without medication ( 17.5 % ) . Other factors responsible for non-adherence included involvement in outdoor business ( 60.87 % ) , ARV stock out ( 37.8 % ) , and not belonging to a support group ( 10.23 % ) . Twenty eight ( 62.22 % ) subjects in the intervention group were able to take their treatment regularly and on time . Conclusion : SMS improved adherence to ARVs . Key constraints which affect adhere to ARV medication can be addressed using SMS Background Applying mobile phones in healthcare is increasingly prioritized to strengthen healthcare systems . Antenatal care has the potential to reduce maternal morbidity and improve newborns ’ survival but this benefit may not be realized in sub-Saharan Africa where the attendance and quality of care is declining . We evaluated the association between a mobile phone intervention and antenatal care in a re source -limited setting . We aim ed to assess antenatal care in a comprehensive way taking into consideration utilisation of antenatal care as well as content and timing of interventions during pregnancy . Methods This study was an open label pragmatic cluster-r and omised controlled trial with primary healthcare facilities in Zanzibar as the unit of r and omisation . 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery . 24 primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text-message and voucher component . Primary outcome measure was four or more antenatal care visits during pregnancy . Secondary outcome measures were tetanus vaccination , preventive treatment for malaria , gestational age at last antenatal care visit , and antepartum referral . Results The mobile phone intervention was associated with an increase in antenatal care attendance . In the intervention group 44 % of the women received four or more antenatal care visits versus 31 % in the control group ( OR , 2.39 ; 95 % CI , 1.03 - 5.55 ) . There was a trend towards improved timing and quality of antenatal care services across all secondary outcome measures although not statistically significant . Conclusions The wired mothers ’ mobile phone intervention significantly increased the proportion of women receiving the recommended four antenatal care visits during pregnancy and there was a trend towards improved quality of care with more women receiving preventive health services , more women attending antenatal care late in pregnancy and more women with antepartum complications identified and referred . Mobile phone applications may contribute towards improved maternal and newborn health and should be considered by policy makers in re source -limited setting s . Trial registration Clinical Trials.gov , NCT01821222 Youth are prolific users of cell phone minutes and text messaging . Numerous programs using short message service text messaging ( SMS ) have been employed to help improve health behaviors and health outcomes . However , we lack information on whether and what type of interaction or engagement with SMS program content is required to realize any benefit . We explored youth engagement with an automated SMS program design ed to supplement a 25-session youth development program with demonstrated efficacy for reductions in teen pregnancy . Using two years of program data , we report on youth participation in design of message content and response frequency to messages among youth enrolled in the intervention arm of a r and omized controlled trial ( RCT ) as one indicator of engagement . There were 221 youth between the ages of 14 - 18 enrolled over two years in the intervention arm of the RCT . Just over half ( 51 % ) were female ; 56 % were Hispanic ; and 27 % African American . Youth were sent 40,006 messages of which 16,501 were considered bi-directional where youth were asked to text a response . Four-fifths ( 82 % ) responded at least once to a text . We found variations in response frequency by gender , age , and ethnicity . The most popular types of messages youth responded to include questions and quizzes . The first two months of the program in each year had the highest response frequency . An important next step is to assess whether higher response to SMS results in greater efficacy . This future work can facilitate greater attention to message design and content to ensure messages are engaging for the intended audience Background Following male circumcision for HIV prevention , a high proportion of men fail to return for their scheduled seven-day post-operative visit . We evaluated the effect of short message service ( SMS ) text messages on attendance at this important visit . Methodology We enrolled 1200 participants > 18 years old in a two-arm , parallel , r and omized controlled trial at 12 sites in Nyanza province , Kenya . Participants received daily SMS text messages for seven days ( n = 600 ) or usual care ( n = 600 ) . The primary outcome was attendance at the scheduled seven-day post-operative visit . The primary analysis was by intention-to-treat . Principal Findings Of participants receiving SMS , 387/592 ( 65.4 % ) returned , compared to 356/596 ( 59.7 % ) in the control group ( relative risk [ RR ] = 1.09 , 95 % confidence interval [ CI ] 1.00–1.20 ; p = 0.04 ) . Men who paid more than US$ 1.25 to travel to clinic were at higher risk for failure to return compared to those who spent ≤US$1.25 ( adjusted relative risk [ aRR ] 1.35 , 95 % CI 1.15–1.58 ; p<0.001 ) . Men with secondary or higher education had a lower risk of failure to return compared to those with primary or less education ( aRR 0.87 , 95 % CI 0.74–1.01 ; p = 0.07 ) . Conclusions Text messaging result ed in a modest improvement in attendance at the 7-day post-operative clinic visit following adult male circumcision . Factors associated with failure to return were mainly structural , and included transportation costs and low educational level . Trial Registration Clinical Trials.gov Background Reminder/recall systems are effective ways to improve immunization rates , but their feasibility in primary health care ( PHC ) setting s in Nigeria has not been adequately evaluated . In this study we describe the acceptability and adaptability of immunization reminder/recall system in an urban setting in southwest Nigeria . Methods This is a descriptive report of a cluster r and omized controlled trial . Four local government areas ( LGAs ) were r and omly assigned into a cellphone reminder/recall intervention group or a usual care control group . Within each LGA , PHC centers were purposively selected to participate in the study . In each PHC center , mothers and their infants aged 0–3 months were enrolled into the two groups during the infants ’ first immunization visit . Mothers ( or other contact persons ) in the intervention group received cellphone calls reminding them to take their child for scheduled immunizations . Follow-up of all the children lasted till the final scheduled immunization visit for each child . The intervention lasted for 13 months . Results A total of 595 mothers/infants pairs ( 295 in the intervention group and 300 in the control group ) participated in the study . Almost all mothers ( n = 590 , 99.2 % ) had access to their own cellphone or had access to a cellphone belonging to a significant other . Ninety-eight percent ( n = 584 ) of all mothers were willing to receive immunization reminder/recall phone calls . Eighty-seven percent ( n = 2023 ) of all calls ( n = 2324 ) for the reminder/recall intervention went through to the recipients and of these calls , 1948 ( 96.3 % ) were received . The mean cost of each call in US Dollars was about 5 cents . Immunization compliance rate ( the receipt of required number of doses of routine vaccines at the appropriate age at recommended interval ) was 79.2 % among the children in intervention group and 46.4 % in the control group ( p < 0.001 ) . Conclusion Results demonstrate that cellphone reminder/recall interventions to improve routine childhood immunization are feasible in PHC setting s in limited-re source setting s with wide cellphone coverage , such as urban areas in Nigeria . Further research to test the potential for scale up in a variety of setting s is recommended . Trial registration PACTR201702002043415 ; Date of registration : 17 February 2017 . ( Retrospectively registered ) A pilot r and omized clinical trial of youth ages 15 - 24 nonadherent to antiretroviral therapy ( ART ) utilizing daily cell phone support was found to have significant improvement in self-reported adherence and HIV RNA . Underst and ing acceptability and feasibility is critical for future implementation in clinic setting s. Exit interviews were obtained from participants and adherence facilitators ( AF ) . Acceptability was assessed from content analysis of exit interviews . Feasibility was assessed via intervention retention and study retention rates . Thirty-seven eligible youth were enrolled with 19 assigned to the intervention . Seven ( 37 % ) discontinued the intervention either due to missing over 20 % of calls for two consecutive months ( N=5 ) or missing 10 consecutive calls ( N=2 ) . Sixteen participants completed exit interviews , 15 reported the call length was just right , 13 reported they would have liked to continue calls after the 24-week intervention , and all participants reported they would recommend the intervention to friends . Scheduling and making calls required less than 1 h per week per participant . Providing cell phone support to youth nonadherent to ART was acceptable and feasible . While the cost is low compared to the price of ART , healthcare systems will need to explore how to cover the cost of providing cell phones ( incentive ) Abstract Introduction : SMS text messaging is increasingly used for delivering smoking cessation support and pilot studies suggest this may also be useful in pregnancy . This study explores the views of women who received a tailored text messaging cessation intervention ( MiQuit ) during pregnancy , focusing on acceptability , perceived impact , and suggestions for improvements . Methods : Semi-structured interviews were undertaken with 15 purposively sample d women who had received the MiQuit intervention during pregnancy as part of a r and omized controlled trial . Data were analyzed thematically . Results : Three main themes were identified : “ impact ” , “ approach , ” and “ optimization . ” Participants described an immediate , yet often short-lived , impact from the texts that distracted and delayed them from smoking and they perceived that texts focusing on the development of and risk to the baby generated more enduring emotional impacts . Most women found receiving support by text preferable to face-to-face cessation support , with participants citing the greater regularity , convenience , and non-judgmental style as particular advantages . Participants would have preferred a longer support program with increased tailoring , greater customization of text timings and consideration of cutting down as an alternative/precursor to quitting . Conclusion : Pregnancy-specific cessation support by text message was well received and participants considered the support increased their motivation to stop smoking . The focus on the developing baby , the regularity of contact and the provision of gentle , encouraging messages were highlighted as particularly important elements of the program . Implication s : This study adds further evidence to the acceptability and perceived positive impact of text-messaging programs in aiding smoking cessation in pregnancy . The findings indicate that for some women , this type of support is preferable to face-to-face methods and could be utilized by health professionals , either in addition to current methods or as an alternative . This study is also relevant to research ers developing health-related text programs to consider participants ’ desire for greater tailoring . Further research is required into adapting and continuing text support for women postpartum Background Intimate partner violence ( IPV ) is common during pregnancy and the postpartum . Perinatal home visitation provides favorable conditions in which to identify and support women affected by IPV . However , the use of mHealth for delivering IPV interventions in perinatal home visiting has not been explored . Objective Our objective was to conduct a nested qualitative interpretive study to explore perinatal home visitors ’ and women ’s perceptions and experiences of the Domestic Violence Enhanced Home Visitation Program ( DOVE ) using mHealth technology ( ie , a computer tablet ) or a home visitor-administered , paper-based method . Methods We used purposive sampling , using maximum variation , to select women enrolled in a US-based r and omized controlled trial of the DOVE intervention for semistructured interviews . Selection criteria were discussed with the trial research team and 32 women were invited to participate . We invited 45 home visitors at the 8 study sites to participate in an interview , along with the 2 DOVE program design ers . Nonparticipant observations of home visits with trial participants who chose not to participate in semistructured interviews were undertaken . Results We conducted 51 interviews with 26 women , 23 home visiting staff at rural and urban sites , and the 2 DOVE program design ers . We conducted 4 nonparticipant observations . Among 18 IPV-positive women , 7 used the computer tablet and 11 used the home visitor method . Among 8 IPV-negative women , 7 used the home visitor method . The computer tablet was viewed as a safe and confidential way for abused women to disclose their experiences without fear of being judged . The meanings that the DOVE technology held for home visitors and women led to its construction as either an impersonal artifact that was an impediment to discussion of IPV or a conduit through which interpersonal connection could be deepened , thereby facilitating discussion about IPV . Women ’s and home visitors ’ comfort with either method of screening was positively influenced by factors such as having established trust and rapport , as well as good interpersonal communication . The technology helped reduce the anticipated stigma associated with disclosing abuse . The didactic intervention video was a limiting feature , as the content could not be tailored to accommo date the fluidity of women ’s circumstances . Conclusions Users and developers of technology-based IPV interventions need to consider the context in which they are being embedded and the importance of the patient-provider relationship in promoting behavior change in order to realize the full benefits . An mHealth approach can and should be used as a tool for initiating discussion about IPV , assisting women in enhancing their safety and exploring help-seeking options . However , training for home visitors is required to ensure that a computer tablet is used to complement and enhance the therapeutic relationship . Clinical Trial Clinical trials.gov NCT01688427 ; https:// clinical trials.gov/ct2/show/NCT01688427 ( Archived by WebCite at http://www.webcitation.org/6limSWdZP OBJECTIVE Measles-mumps-rubella ( MMR ) vaccination is important for preventing disease outbreaks , yet pockets of under-vaccination persist . Text message reminders have been employed successfully for other pediatric vaccines , but studies examining their use for MMR vaccination are limited . This study assessed the impact of text message reminders on timely MMR vaccination . STUDY DESIGN Parents ( n=2054 ) of 9.5 - 10.5-month-old children from four urban academically-affiliated pediatric clinics were r and omized to scheduling plus appointment text message reminders , appointment text message reminder-only , or usual care . The former included up to three text reminders to schedule the one-year preventive care visit . Both text messaging arms included a text reminder sent 2 days before that visit . Outcomes included appointment scheduling , appointment attendance , and MMR vaccination by age 13 months , the st and ard of care at study sites . RESULTS Children of parents in the scheduling plus appointment text message reminders arm were more likely to have a scheduled one-year visit than those in the other arms ( 71.9 % vs. 67.4 % , relative risk ratio ( RRR ) 1.07 [ 95 % CI 1.005 - 1.13 ] ) , particularly if no appointment was scheduled before r and omization ( i.e. , no baseline appointment ) ( 62.1 % vs. 54.7 % , RRR 1.14 [ 95 % CI 1.04 - 1.24 ] ) . One-year visit attendance and timely MMR vaccination were similar between arms . However , among children without a baseline appointment , those with parents in the scheduling plus appointment text message reminders arm were more likely to undergo timely MMR vaccination ( 61.1 % vs. 55.1 % , RRR 1.11 [ 95 % CI 1.01 - 1.21 ] ) . CONCLUSION Text message reminders improved timely MMR vaccination of high-risk children without a baseline one-year visit Purpose Medication adherence is a major challenge in HIV treatment . New mobile technologies such as smartphones facilitate the delivery of brief tailored messages to promote adherence . However , the best approach for tailoring messages is unknown . Persons living with HIV ( PLWH ) might be more receptive to some messages than others based on their current psychological state . Methods We recruited 37 PLWH from a parent study of motivational states and adherence . Participants completed smartphone-based surveys at a r and om time every day for 2 weeks , then immediately received intervention or control tailored messages , depending on r and om assignment . After 2 weeks in the initial condition , participants received the other condition in a crossover design . Intervention messages were tailored to match PLWH ’s current psychological state based on five variables – control beliefs , mood , stress , coping , and social support . Control messages were tailored to create a mismatch between message framing and participants ’ current psychological state . We evaluated intervention feasibility based on acceptance , ease of use , and usefulness measures . We also used pilot r and omized controlled trial methods to test the intervention ’s effect on adherence , which was measured using electronic caps that recorded pill-bottle openings . Results Acceptance was high based on 76 % enrollment and 85 % satisfaction . Participants found the hardware and software easy to use . However , attrition was high at 59 % , and usefulness ratings were slightly lower . The most common complaint was boredom . Unexpectedly , there was no difference between mismatched and matched messages ’ effects , but each group showed a 10%–15 % improvement in adherence after crossing to the opposite study condition . Conclusion Although smartphone-based tailored messaging was feasible and participants had clinical ly meaningful improvements in adherence , the mechanisms of change require further study . Possible explanations might include novelty effects , increased receptiveness to new information after habituation , or pseudotailoring , three ways in which attentional processes can affect behavior Abstract Aims To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service ( SMS ) text message and key parameters needed to plan a definitive trial . Design Multi‐centre , parallel‐group , single‐blinded , individual r and omized controlled trial . Setting Sixteen antenatal clinics in Engl and . Participants Four hundred and seven participants were r and omized to the intervention ( n = 203 ) or usual care ( n = 204 ) . Eligible women were < 25 weeks gestation , smoked at least one daily cigarette ( > 5 pre‐pregnancy ) , were able to receive and underst and English SMS texts and were not already using text‐based cessation support . Intervention All participants received a smoking cessation leaflet ; intervention participants also received a 12‐week programme of individually tailored , automated , interactive , self‐help smoking cessation text messages ( MiQuit ) . Outcome measurements Seven smoking outcomes , including vali date d continuous abstinence from 4 weeks post‐r and omization until 36 weeks gestation , design parameters for a future trial and cost‐per‐quitter . Findings Using the vali date d , continuous abstinence outcome , 5.4 % ( 11 of 203 ) of MiQuit participants were abstinent versus 2.0 % ( four of 204 ) of usual care participants [ odds ratio ( OR ) = 2.7 , 95 % confidence interval ( CI ) = 0.93–9.35 ] . The Bayes factor for this outcome was 2.23 . Completeness of follow‐up at 36 weeks gestation was similar in both groups ; provision of self‐report smoking data was 64 % ( MiQuit ) and 65 % ( usual care ) and abstinence validation rates were 56 % ( MiQuit ) and 61 % ( usual care ) . The incremental cost‐per‐quitter was £ 133.53 ( 95 % CI = –£395.78 to 843.62 ) . Conclusions There was some evidence , although not conclusive , that a text‐messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care OBJECTIVE To compare the effectiveness of different methods of recall for repeat Pap smear among women who had normal smears in the previous screening . DESIGN Prospect i ve r and omized controlled study . SETTING All community clinics in Klang under the Ministry of Health Malaysia . PARTICIPANTS Women of Klang who attended cervical screening and had a normal Pap smear in the previous year , and were due for a repeat smear were recruited and r and omly assigned to four different methods of recall for repeat smear . INTERVENTION The recall methods given to the women to remind them for a repeat smear were either by postal letter , registered letter , short message by phone ( SMS ) or phone call . MAIN OUTCOME MEASURES Number and percentage of women who responded to the recall within 8 weeks after they had received the recall , irrespective whether they had Pap test conducted . Also the numbers of women in each recall method that came for repeat Pap smear . RESULTS The rates of recall messages reaching the women when using letter , registered letter , SMS and phone calls were 79 % , 87 % , 66 % and 68 % , respectively . However , the positive responses to recall by letter , registered letter , phone messages and telephone call were 23.9 % , 23.0 % , 32.9 % and 50.9 % , respectively ( p<0.05 ) . Furthermore , more women who received recall by phone call had been screened ( p<0.05 ) compared to those who received recall by postal letter ( OR=2.38 , CI=1.56 - 3.62 ) . CONCLUSION Both the usual way of sending letters and registered letters had higher chances of reaching patients compared to using phone either for sending messages or calling . The response to the recall method and uptake of repeat smear , however , were highest via phone call , indicating the importance of direct communication Background For youth living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome ( AIDS ) , nonadherence to antiretroviral therapy ( ART ) can lead to poor health outcomes and significantly decreased life expectancy . Objective To evaluate the feasability , acceptability , and preliminary efficacy of short message service ( SMS ) or text message reminders to improve adherence to ART for youth living with HIV/AIDS . Methods We conducted this prospect i ve pilot study using a pre – post design from 2009 to 2010 at a community-based health center providing clinical services to youth living with HIV/AIDS . Eligibility criteria included HIV-positive serostatus , age 14–29 years , use of a personal cell phone , English-speaking , and being on ART with documented poor adherence . During the 24-week study period , participants received personalized daily SMS reminders and a follow-up message 1 hour later assessing whether they took the medication , and asking participants to respond via text message with the number 1 if they took the medication and 2 if they did not . Outcome measures were feasibility , acceptability , and adherence . Self-reported adherence was determined using the visual analog scale ( VAS ) and AIDS Clinical Trial Group ( ACTG ) question naire 4-day recall . Viral load and CD4 cell count were followed as biomarkers of adherence and disease progression at 0 , 12 , and 24 weeks . Results Participants ( N = 25 ) were mean age 23 ( range 14–29 ) years , 92 % ( n = 23 ) male , 60 % ( n = 15 ) black , and 84 % ( n = 21 ) infected through unprotected sex . Mean VAS scores significantly increased at 12 and 24 weeks in comparison with baseline ( week 0 : 74.7 , week 12 : 93.3 , P < .001 ; week 24 : 93.1 , P < .001 ) . ACTG question naire 4-day recall also improved ( week 0 : 2.33 , week 12 : 3.24 , P = .002 ; week 24 : 3.19 , P = .005 ) . There was no significant difference in CD4 cell count or viral load between baseline and 12- or 24-week follow-up , although there was a trend toward improvement of these biomarkers and a small to moderate st and ardized effect size ( range of Cohen d : –0.51 to 0.22 ) . Of 25 participants , 21 ( 84 % ) were retained , and 20 of the 21 ( 95 % ) participants who completed the study found the intervention helpful to avoid missing doses . Conclusions In this pilot study , personalized , interactive , daily SMS reminders were feasible and acceptable , and they significantly improved self-reported adherence . Larger controlled studies are needed to determine the impact of this intervention on ART adherence and other related health outcomes for youth living with HIV/AIDS Background The use of mobile phone technologies for health promotion and disease prevention has advanced rapidly in recent years . Text4baby is a theory-based mobile health ( mHealth ) program in which text messages are delivered to pregnant women and new mothers to improve their health care beliefs and behaviors and improve health status and clinical outcomes . Recent evaluations of Text4baby have found that it improves targeted health attitudes and beliefs , but effects on behavior have not yet been determined . Objective In this study , investigators aim ed to evaluate Text4baby in the military women ’s population . Methods Investigators conducted a r and omized controlled trial at Madigan Army Medical Center in Tacoma , Washington , from December 2011 through September 2013 . All participants were pregnant women first presenting for care at Madigan . Investigators conducted a baseline assessment using a 24-item , self-administered online survey of attitudes and behaviors related to Text4baby message content . Participants were r and omized to Text4baby plus usual care ( intervention ) or usual care alone ( control ) . Investigators analyzed treatment effects of Text4baby on short-term targeted outcomes 4 weeks post enrollment . Results For this study , 943 patients were r and omized and completed a baseline assessment . The average patient age was 28 years and nearly 70 % self-identified as Caucasian . 48.7 % of enrollees ( 459/943 ) completed the first follow-up assessment . Higher rates of single and working/in-school patients dropped out of the intervention arm of the study , and we adjusted for this finding in subsequent models . However , while investigators were unable to re-survey these participants , only 1.9 % of Text4baby enrollees ( 18/943 ) dropped the service during the study period . Adjusted and unadjusted logistic generalized estimating equation models were developed to assess intervention effects on measured outcomes . In the model adjusting for age , marital status , having had a previous baby , and race/ethnicity , there was a significant effect of Text4baby intervention exposure on increased agreement with belief in the importance of taking prenatal vitamins ( OR 1.91 , 95 % CI 1.08 - 3.34 , P=.024 ) . All of these attitudes had been targeted by at least one text message during the 4-week evaluation period examined in this study . In unadjusted models , there was a significant effect of intervention exposure on belief in the importance of visiting a health care provider to be a healthy new mother ( OR 1.52 , 95 % CI 1.01 - 2.31 , P=.046 ) and in the health risks of alcohol during pregnancy ( OR 2.06 , 95 % CI 1.00 - 4.31 , P=.05 ) . No behavioral effects of the intervention were observed in this analysis . Conclusions Text4baby is a promising program that offers lessons for future mHealth activities . This large-scale study demonstrated initial effects of the program on attitudes and beliefs targeted by the messages received by women during the study period . Results confirm previous findings from Text4baby studies and other mHealth research . Future analyses will examine dosage effects of the intervention on behaviors and clinical outcomes Summary Background As mobile phone access continues to exp and globally , opportunities exist to leverage these technologies to support dem and for immunisation services and improve vaccine coverage . We aim ed to assess whether short message service ( SMS ) reminders and monetary incentives can improve immunisation uptake in Kenya . Methods In this cluster-r and omised controlled trial , villages were r and omly and evenly allocated to four groups : control , SMS only , SMS plus a 75 Kenya Shilling ( KES ) incentive , and SMS plus 200 KES ( 85 KES = USD$1 ) . Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine . Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits . Participants in incentive groups , additionally , received money if their child was timely immunised ( immunisation within 2 weeks of the due date ) . Caregivers and interviewers were not masked . The proportion of fully immunised children ( receiving BCG , three doses of polio vaccine , three doses of pentavalent vaccine , and measles vaccine ) by 12 months of age constituted the primary outcome and was analysed with log-binomial regression and General Estimating Equations to account for correlation within clusters . This trial is registered with Clinical Trials.gov , number NCT01878435 . Findings Between Oct 14 , 2013 , and Oct 17 , 2014 , we enrolled 2018 caregivers and their infants from 152 villages into the following four groups : control ( n=489 ) , SMS only ( n=476 ) , SMS plus 75 KES ( n=562 ) , and SMS plus 200 KES ( n=491 ) . Overall , 1375 ( 86 % ) of 1600 children who were successfully followed up achieved the primary outcome , full immunisation by 12 months of age ( 296 [ 82 % ] of 360 control participants , 332 [ 86 % ] of 388 SMS only participants , 383 [ 86 % ] of 446 SMS plus 75 KES participants , and 364 [ 90 % ] of 406 SMS plus 200 KES participants ) . Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age ( relative risk 1·09 , 95 % CI 1·02–1·16 , p=0·014 ) than children in the control group . Interpretation In a setting with high baseline immunisation coverage levels , SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness . Given that global immunisation coverage levels have stagnated around 85 % , the use of incentives might be one option to reach the remaining 15 % . Funding Bill & Melinda Gates Foundation OBJECTIVE : To estimate whether women receiving daily text-message reminders have increased oral contraceptive pill adherence compared with women not receiving reminders . METHODS : This r and omized controlled trial estimated whether there was an effect of daily text-message reminders on oral contraceptive pill adherence of new oral contraceptive pill users . Pill-taking was tracked for 3 months by an electronic monitoring device with wireless data collection . During the study period , participants assigned the intervention received a daily reminder text message . Eighty-two women were assigned r and omly to detect a 1.6±2.0 pill difference ( 90 % power , 5 % & agr ; , 15 % dropout ) . RESULTS : Participants were 79 % white , non-Hispanic , 99 % high school graduates , and 99 % nulliparous with a mean age of 22 years . Most reported condom use with past coital activity , and more than half reported prior emergency contraception use . The mean number of missed pills per cycle did not differ significantly between the groups : 4.9±3.0 for the text-message group and 4.6±3.5 for the control group ( P=.60 ) . The number of missed pills per cycle increased over the course of the study , but this pattern did not increase differentially between the groups . Adherence recorded by the electronic monitoring device indicated much poorer adherence than that recorded by patient diaries . Despite poor pill-taking , there were no pregnancies . CONCLUSION : Daily text-message reminders did not improve oral contraceptive pill adherence . Although the lack of benefit may be attributed to the frequent use of alternative reminder systems in the control group , the rate of missed pills when measured objective ly was still very high in both groups . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00733707 . LEVEL OF EVIDENCE : OBJECTIVE : To estimate whether daily educational text messages affect oral contraceptive pill ( OCP ) continuation at 6 months . METHODS : We r and omized young women electing OCPs at an urban family planning health center to either routine care or routine care plus 180 days of daily educational text messages . Investigators masked to treatment allocation r and omized participants who were not masked to treatment . The primary outcome measure was self-reported OCP continuation through a telephone call at 6 months ( contacts between 5 and 8 months ) . RESULTS : We enrolled 962 participants ( 480 intervention and 482 routine care ) and obtained continuation data on 683 ( 346 and 337 , respectively ) . At the follow-up , 64 % of participants r and omized to the intervention were still OCP users compared with 54 % of the routine care group ( P=.005 ) . Continuation was highest in the intervention group if the interview took place while the intervention was ongoing ( 75 % compared with 54 % , P=.003 ) ; the effect of the intervention on continuation was less after the intervention ended ( 60 % compared with 54 % , P=.16 ) . Participants receiving the intervention were more likely to continue oral contraception than control participants at 6 months ( odds ratio 1.44 , 95 % confidence interval 1.03–2.00 ) in analyses adjusted for age , race or ethnicity , age at coitarche , pregnancy history , and OCP experience . CONCLUSION : The use of daily educational text messages improves OCP continuation at 6 months over routine care alone . Ten women would need to receive this simple intervention to improve continuation in one . This effect is strongest in the women whose follow-up took place while the text intervention was ongoing . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . Clinical Trials.gov , NCT00677703 . LEVEL OF EVIDENCE : Youth living with HIV/AIDS ( YLH ) face unique challenges to optimal adherence to antiretroviral therapy ( ART ) . Accurate , real-time methods to assess adherence are needed to facilitate early intervention and promote viral suppression . The purpose of this study was to assess the feasibility and validity of interactive text message response ( ITR ) as a measure of adherence to ART among YLH . This study was part of a larger pilot text message reminder intervention conducted at a US community-based , LGBT-focused health center providing clinical services to YLH . Eligibility criteria for this pilot study included HIV-positive serostatus , aged 14–29 , use of personal cell phone , English-speaking , and on ART with demonstrated adherence difficulties . During the 24-week study period , participants received personalized daily short message system reminders with a follow-up message 1 hour later asking whether they took medication and directing a response via return text message . To determine whether or not ITR would be a feasible , valid measure of adherence , we calculated the proportion of positive responses indicating medication had been taken divided by the total number of messages requesting a response and compared this response rate to a self-reported adherence measure , the visual analogue scale ( VAS ) . Participants ( n = 25 ) were on average 23 years old , largely male ( 92 % ) , Black ( 60 % ) and behaviorally infected ( 84 % ) . Over the course of the intervention , study participants responded to prompts via text to indicate whether or not they had taken their medication approximately 61 % of the time . The overall mean ITR adherence rate ( i.e. , positive responses ) was 57.4 % ( SD = 28.5 % ) . ITR and VAS measures were moderately , positively correlated ( r = 0.52 , p < 0.05 ) during the first 6 weeks of the study period . ITR adherence rates were significantly higher on weekdays versus weekends ( p < 0.05 ) . This pilot study showed both moderate responsiveness of individuals to daily ITR and a moderate correlation of ITR adherence rates with a reliable measure during the first 6 weeks of the study , suggesting that this method , with additional effort and improvements , may be a helpful tool to identify and respond to adherence patterns in real-time Objective : We evaluated whether regular mobile phone text reminders improved patients ' retention in antiretroviral therapy ( ART ) care in Mozambique . Design : SMSaúde was a r and omized control trial of HIV-infected patients on ART who received regular text message reminder vs. st and ard of care at 3 public health facilities in Maputo Province , Mozambique . The primary outcome was retention in HIV care . Between November 2011 and March 2012 , 830 eligible HIV-infected patients on ART were r and omized 1:1 to the text reminder intervention or st and ard of care . Methods : We used Kaplan – Meier estimators and log-rank tests to compare proportions of patients who received SMS reminders who were retained in HIV care compared to the control group who received st and ard of care . Post hoc analyses were performed using Cox proportional hazards models stratified by urban/rural facility and when initiated ART ( ⩽3 months vs. > 3 months ) . Hazard ratios and confidence intervals ( CIs ) are reported . Analysis was with intention to treat . Results : Patients who received text messages had lower attrition from HIV care at 12 months , though the difference was nonsignificant ( RR : 0.68 , 95 % CI : 0.41 to 1.13 ) . Among urban patients , text messages improved retention in HIV care ( RR : 0.54 , 95 % CI : 0.31 to 0.95 ) . Intervention patients newly initiated on ART ( <3 months ) had lower attrition than control patients ( HR : 0.54 ; 95 % CI : 0.23 to 0.91 ) , especially urban newly initiated patients ( HR : 0.20 , 95 % CI : 0.06 to 0.64 ) . Text messages had no effect on retention among rural patients . Conclusions : Text messages did not improve retention in HIV care for all patients on ART but improved retention in care of urban patients and those who recently started ART and received text reminders compared with st and ard of care Background HIV-related mHealth interventions have demonstrable efficacy in supporting treatment adherence , although the evidence base for promoting HIV testing is inconclusive . Progress is constrained by a limited underst and ing of processes used to develop interventions and weak theoretical underpinnings . This paper describes a research project that informed the development of a theory-based mHealth intervention to promote HIV testing amongst city-dwelling African communities in the UK . Methods A community-based participatory social marketing design was adopted . Six focus groups ( 48 participants in total ) were undertaken and analysed using a thematic framework approach , guided by constructs from the Health Belief Model . Key themes were incorporated into a set of text messages , which were pre-tested and refined . Results The focus groups identified a relatively low perception of HIV risk , especially amongst men , and a range of social and structural barriers to HIV testing . In terms of self-efficacy around HIV testing , respondents highlighted a need for communities and professionals to work together to build a context of trust through co-location in , and co-involvement of , local communities which would in turn enhance confidence in , and support for , HIV testing activities of health professionals . Findings suggested that messages should : avoid an exclusive focus on HIV , be tailored and personalised , come from a trusted source , allay fears and focus on support and health benefits . Conclusions HIV remains a stigmatized and de-prioritized issue within African migrant communities in the UK , posing barriers to HIV testing initiatives . A community-based participatory social marketing design can be successfully used to develop a culturally appropriate text messaging HIV intervention . Key challenges involved turning community research recommendations into brief text messages of only 160 characters . The intervention needs to be evaluated in a r and omized control trial . Future research should explore the application of the processes and method ologies described in this paper within other communities Objective To assess whether customised mobile phone reminders would improve adherence to therapy and thus decrease virological failure among HIV infected patients starting antiretroviral treatment ( ART ) . Design R and omised controlled trial among HIV infected patients initiating antiretroviral treatment . Setting Three diverse healthcare delivery setting s in south India : two ambulatory clinics within the Indian national programme and one private HIV healthcare clinic . Participants 631 HIV infected , ART naïve , adult patients eligible to initiate first line ART were r and omly assigned to mobile phone intervention ( n=315 ) or st and ard care ( n=316 ) and followed for 96 weeks .. Intervention The intervention consisted of customised , interactive , automated voice reminders , and a pictorial message that were sent weekly to the patients ’ mobile phones for the duration of the study . Main outcome measures The primary outcome was time to virological failure ( viral load > 400 copies/mL on two consecutive measurements ) . Secondary outcomes included ART adherence measured by pill count , death rate , and attrition rate . Suboptimal adherence was defined as mean adherence < 95 % . Results Using an intention-to-treat approach we found no observed difference in time to virological failure between the allocation groups : failures in the intervention and st and ard care arms were 49/315 ( 15.6 % ) and 49/316 ( 15.5 % ) respectively ( unadjusted hazard ratio 0.98 , 95 % confidence interval 0.67 to 1.47 , P=0.95 ) . The rate of virological failure in the intervention and st and ard care groups were 10.52 and 10.73 per 100 person years respectively . Comparison of suboptimal adherence was similar between both groups ( unadjusted incidence rate ratio 1.24 , 95 % CI 0.93 to 1.65 , P=0.14 ) . Incidence proportion of patients with suboptimal adherence was 81/300 ( 27.0 % ) in the intervention arm and 65/299 ( 21.7 % ) in the st and ard care arm . The results of analyses adjusted for potential confounders were similar , indicating no significant difference between the allocation groups . Other secondary outcomes such as death and attrition rates , and subgroup analysis also showed comparable results across allocation groups . Conclusions In this multicentre r and omised controlled trial among ART naïve patients initiating first line ART within the Indian national programme , we found no significant effect of the mobile phone intervention on either time to virological failure or ART adherence at the end of two years of therapy . Trial registration Current Controlled Trials IS RCT N79261738 Mobile phone text messages ( SMS ) are a promising method of health promotion , but a simple and low cost way to obtain phone numbers is required to reach a wide population . We conducted a r and omised controlled trial with simultaneous brief interventions to ( i ) evaluate effectiveness of messages related to safer sex and sun safety and ( ii ) pilot the use of mobile advertising for health promotion . Mobile advertising subscribers aged 16 - 29 years residing in Victoria , Australia ( n = 7606 ) were r and omised to the ' sex ' or ' sun ' group and received eight messages during the 2008 - 2009 summer period . Changes in sex- and sun-related knowledge and behaviour were measured by question naires completed on mobile phones . At follow-up , the sex group had significantly higher sexual health knowledge and fewer sexual partners than the sun group . The sun group had no change in hat-wearing frequency compared with a significant decline in hat-wearing frequency in the sex group . This is the first study of mobile advertising for health promotion , which can successfully reach most young people . Challenges experienced with project implementation and evaluation should be considered as new technological approaches to health promotion continue to be exp and ed OBJECTIVE This pilot study tested the preliminary efficacy of a theory-based bidirectional text messaging intervention ( TEXT ) on antiretroviral ( ART ) adherence , missed care visits , and substance use among people with HIV . METHOD Participants with recent substance use and ART nonadherence from 2 nonurban HIV clinics were r and omized to TEXT or to usual care ( UC ) . The TEXT intervention included daily queries of ART adherence , mood , and substance use . The system sent contingent intervention messages created by participants for reports of adherence/nonadherence , good mood/poor mood , and no substance use/use . Assessment s were at preintervention , postintervention , and 3-month postintervention follow-up . Objective primary outcomes were adherence , measured by past 3-month pharmacy refill rate , and proportion of missed visits ( PMV ) , measured by medical records . The rate of substance-using days from the timeline follow-back was a secondary outcome . RESULTS Sixty-three patients participated , with 33 r and omized to TEXT and 30 to UC . At preintervention , adherence was 64.0 % , PMV was 26.9 % , and proportion of days using substances was 53.0 % . At postintervention , adherence in the TEXT condition improved from 66 % to 85 % , compared with 62 % to 71 % in UC participants ( p = .04 ) . PMV improved from 23 % to 9 % for TEXT participants and 31 % to 28 % in UC participants ( p = .12 ) . There were no significant differences between conditions in substance-using days at postintervention . At 3-month follow-up , differences were not significant . CONCLUSIONS Personalized bidirectional text messaging improved adherence and shows promise to improve visit attendance , but did not reduce substance using days . This intervention merits further testing and may be cost-efficient given its automation Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting OBJECTIVE South Africa has one of the highest human immunodeficiency virus ( HIV ) prevalence rates in the world , but despite the well-established benefits of HIV counseling and testing ( HCT ) , there is low uptake of HCT . The study aim ed to investigate the effectiveness of using short message services ( SMSs ) to encourage HCT while interrogating the impact of altering SMS content and dosage ( the number of SMSs ) . MATERIAL S AND METHODS About 2,533 participants were recruited via an SMS sent to 24,000 mobiles r and omly sample d from a pre-existing data base . Recruits were r and omly allocated to four intervention groups that received 3 or 10 informational ( INFO ) or motivational ( MOTI ) SMSs , and a control group . After the intervention , participants were prompted to go for HCT , and postintervention assessment was done after 3 weeks . RESULTS In comparison with the control , receipt of 10 MOTI messages had the most impact on uptake of HCT with a 1.7-fold increased odds of testing ( confidence interval 95 % ; p=0.0036 ) . The lack of efficacy of three SMSs indicates a threshold effect , that is , a minimum number of MOTI SMSs is required . INFO SMSs , whether 3 or 10 were sent , did not have a statistically significant effect . The cost can be calculated for the marginal effect of the SMSs , that is , the cost to get people to test over and above those who were likely to test without the intervention . Use of 10 MOTI SMSs yielded a cost-per-tester of $ 2.41 . CONCLUSIONS While there are method ological issues apparent in our study , the results demonstrate the potential of SMSs to influence the uptake of HCT , the importance of appropriate content , and the need to determine a threshold for SMS-based interventions . These results indicate a potential for SMSs to be used more generally for interventions encouraging people to take health-related actions , and the need for further research in this field . The reasonable cost-per-tester is promising for the scale-up of such an intervention PURPOSE To improve adolescent notification of positive sexually transmitted infection ( STI ) tests using mobile phone technology and STI information cards . METHODS A r and omized intervention among 14- to 21-year olds in a pediatric emergency department ( PED ) . A 2 × 3 factorial design with replication was used to evaluate the effectiveness of six combinations of two factors on the proportion of STI-positive adolescents notified within 7 days of testing . Independent factors included method of notification ( call , text message , or call + text message ) and provision of an STI information card with or without a phone number to obtain results . Covariates for logistic regression included age , empiric STI treatment , days until first attempted notification , and documentation of confidential phone number . RESULTS Approximately half of the 383 females and 201 males enrolled were ≥18 years of age . Texting only or type of card was not significantly associated with patient notification rates , and there was no significant interaction between card and notification method . For females , successful notification was significantly greater for call + text message ( odds ratio , 3.2 ; 95 % confidence interval , 1.4 - 6.9 ) , and documenting a confidential phone number was independently associated with successful notification ( odds ratio , 3.6 ; 95 % confidence interval , 1.7 - 7.5 ) . We found no significant predictors of successful notification for males . Of patients with a documented confidential phone number who received a call + text message , 94 % of females and 83 % of males were successfully notified . CONCLUSIONS Obtaining a confidential phone number and using call + text message improved STI notification rates among female but not male adolescents in a pediatric emergency department Abstract Objective To assess the effect of a mobile phone-based intervention ( mHealth ) on post-abortion contraception use by women in Cambodia . Methods The Mobile Technology for Improved Family Planning ( MOTIF ) study involved women who sought safe abortion services at four Marie Stopes International clinics in Cambodia . We r and omly allocated 249 women to a mobile phone-based intervention , which comprised six automated , interactive voice messages with counsellor phone support , as required , whereas 251 women were allocated to a control group receiving st and ard care . The primary outcome was the self-reported use of an effective contraceptive method , 4 and 12 months after an abortion . Findings Data on effective contraceptive use were available for 431 ( 86 % ) participants at 4 months and 328 ( 66 % ) at 12 months . Significantly more women in the intervention than the control group reported effective contraception use at 4 months ( 64 % versus 46 % , respectively ; relative risk , RR : 1.39 ; 95 % confidence interval , CI : 1.17–1.66 ) but not at 12 months ( 50 % versus 43 % , respectively ; RR : 1.16 ; 95 % CI : 0.92–1.47 ) . However , significantly more women in the intervention group reported using a long-acting contraceptive method at both follow-up times . There was no significant difference between the groups in repeat pregnancies or abortions at 4 or 12 months . Conclusion Adding a mobile phone-based intervention to abortion care services in Cambodia had a short-term effect on the overall use of any effective contraception , while the use of long-acting contraceptive methods lasted throughout the study period PURPOSE To pilot test a text message ( SMS ) sex risk reduction program among at-risk young adult female patients discharged from an emergency department ( ED ) . METHODS A convenience sample of 52 female patients with hazardous drinking behavior and recent risky sexual encounters were recruited from an urban ED and r and omized to the SMS program ( n = 23 ) or a control group ( n = 29 ) . All participants completed a web-based question naire in the ED and at 3-month follow-up . For 12 weeks , SMS participants were asked to report whether they had a risky sexual encounter in the past week , received theory-based feedback , and were asked if they were willing set a goal to refrain from having another risky encounter . RESULTS Thirty-nine percent of SMS participants completed all weeks of SMS reports , and noncompletion increasing from 12 % on week 1 to a 33 % by week 12 . Three-month follow-up was completed in 56 % of participants . In the intervention group , there was an increase in the proportion with condom use with last vaginal sex from 20 % ( 95 % CI 4%-48 % ) to 53 % ( 95 % CI 27%-79 % ) and an increase in always condom use over the past 28 days from 0 % ( 95 % CI 0%-22 % ) to 33 % ( 95 % CI 12%-62 % ) . These changes were not statistically different from control participants . CONCLUSIONS SMS programs may be useful to reduce risk for sexually transmitted diseases among at-risk young adults being discharged from the ED . Future trials should examine ways to improve adherence to SMS dialog over time and measure objective outcomes in a larger sample Background Smoking in pregnancy is a public health problem . Self-help smoking cessation support can help pregnant women to stop smoking , but the effects of delivering this kind of support via SMS text message are not known . A previous r and omised controlled trial ( RCT ) demonstrated the feasibility and acceptability of providing such support to pregnant smokers using an automated , tailored text message intervention called MiQuit . This larger RCT will estimate key parameters for and will test the feasibility of delivering a major trial run within the United Kingdom National Health Service setting s aim ed at providing definitive evidence on the utility of MiQuit for helping pregnant smokers to stop . Methods / Design This will be a multi-centre , parallel group RCT . Participants are being identified in 16 English antenatal care setting s and must be > 16 years old , pregnant , < 25 weeks gestation , smoke > 1 daily cigarette , have smoked > 5 daily cigarettes before pregnancy , and able to underst and texts in English . After consenting and the collection of baseline data , participants are r and omised to control or intervention groups in a 1:1 ratio ; r and omisation is stratified by trial site and gestation and employs computer-generated pseudo-r and om code using r and om permuted blocks of r and omly varying size , and held on a secure server . All participants receive a National Health Service ( NHS ) leaflet aim ed at helping them to stop smoking . Intervention group women also receive the 12-week MiQuit programme of tailored , supportive , interactive text message , self-help cessation support . Women are followed up by telephone 4 weeks after r and omisation and at 36 weeks gestation . The study aims to recruit 400 women , and with this sample we will be able to estimate trial centres ’ recruitment rates to within + /−1 % ( margin of error = half width of 95 % confidence interval ) ; individual trial groups ’ ascertainment of rates for smoking outcomes between 4 weeks after r and omisation until approximately 36 weeks gestation to within + /−4 % , and across both groups , the combined cessation rate at 36 weeks + /−3 % . Discussion Pilot trial completion will provide data to facilitate planning for a definitive trial investigating whether MiQuit works for smoking cessation in pregnancy . Trial registration Clinical Trials.gov NCT02043509 Registered 14 January 2014 Background Following HIV-1 acquisition , many individuals develop an acute retroviral syndrome and a majority seek care . Available antibody testing can not detect an acute HIV infection , but repeat testing after 2–4 weeks may detect seroconversion . We assessed the effect of appointment reminders on attendance for repeat HIV testing . Methods We enrolled , in a r and omized controlled trial , 18–29 year old patients evaluated for acute HIV infection at five sites in Coastal Kenya ( Clinical Trials.gov NCT01876199 ) . Participants were allocated 1:1 to either st and ard appointment ( a date d appointment card ) or enhanced appointment ( a date d appointment card plus SMS and phone call reminders , or in-person reminders for participants without a phone ) . The primary outcome was visit attendance , i.e. , the proportion of participants attending the repeat test visit . Factors associated with attendance were examined by bivariable and multivariable logistic regression . Principal Findings Between April and July 2013 , 410 participants were r and omized . Attendance was 41 % ( 85/207 ) for the st and ard group and 59 % ( 117/199 ) for the enhanced group , for a relative risk of 1.4 [ 95 % Confidence Interval , CI , 1.2–1.7].Higher attendance was independently associated with older age , study site , and report of transactional sex in past month . Lower attendance was associated with reporting multiple partners in the past two months . Conclusions Appointment reminders through SMS , phone calls and in-person reminders increased the uptake of repeat HIV test by forty percent . This low-cost intervention could facilitate detection of acute HIV infections and uptake of recommended repeat testing . Trial Registration Clinical trials.gov OBJECTIVE : To determine whether provision of vaccine-health-literacy-promoting information in text message vaccine reminders improves receipt and timeliness of the second dose of influenza vaccine within a season for children in need of 2 doses . METHODS : During the 2012–2013 season , families of eligible 6-month through 8-year-old children were recruited at the time of their first influenza vaccination from 3 community clinics in New York City . Children ( n = 660 ) were r and omly assigned to “ educational ” text message , “ conventional ” text message , and “ written reminder-only ” arms . At enrollment , all arms received a written reminder with next dose due date . Conventional messages included second dose due date and clinic walk-in hours . Educational messages added information regarding the need for a timely second dose . Receipt of second dose by April 30 was assessed by using χ2 tests . Timeliness was assessed by receipt of second dose by 2 weeks after due date ( day 42 ) using χ2 and over time using a Kaplan-Meier analysis . RESULTS : Most families were Latino and publicly insured with no significant between-arm differences between groups . Children in the educational arm were more likely to receive a second dose by April 30 ( 72.7 % ) versus conventional ( 66.7 % ) versus written reminder-only arm ( 57.1 % ; P = .003 ) . They also had more timely receipt by day 42 ( P < .001 ) and over time ( P < .001 ) . CONCLUSIONS : In this low-income , urban , minority population , embedding health literacy information improved the effectiveness of text message reminders in promoting timely delivery of a second dose of influenza vaccine , compared with conventional text messages and written reminder only Background Mobile health ( mHealth ) is growing rapidly , but more studies are needed on how to optimize programs , including optimal timing of messaging , dose of exposure , and value of interactive features . This study evaluates final outcomes of text4baby ( a text message service for pregnant and postpartum women ) from a r and omized trial performed in a population of pregnant female soldiers and family members . Objective The study aims were to evaluate ( 1 ) treatment effects and ( 2 ) dose-response effects of text4baby on behavioral outcomes compared to control ( no text4baby ) condition . Methods The study was a r and omized trial of text4baby at Madigan Army Medical Center . Female military health beneficiaries who met inclusion criteria were eligible for the study . Participants provided consent , completed a baseline question naire , and then were r and omized to enroll in text4baby or not . They were followed up at 3 time points thereafter through delivery of their baby . Generalized estimating equation models were used to evaluate outcomes . We examined treatment effects and the effects of higher doses of text4baby messages on outcomes . Results We report descriptive statistics including dosage of text messages delivered . The main finding was a significant effect of high exposure to text4baby on self-reported alcohol consumption postpartum ( OR 0.212 , 95 % CI 0.046 - 0.973 , P=.046 ) , as measured by the question “ Since you found out about your pregnancy , have you consumed alcoholic beverages ? ” The text4baby participants also reported lower quantities of alcohol consumed postpartum . Conclusions Studies of text4baby have helped to build the mHealth evidence base . The effects of text4baby offer lessons for future scalable mHealth programs and suggest the need to study dose-response effects of these interventions Objective : To underst and how a pilot intervention combining SMS reminders with real-time adherence monitoring improved adherence to HIV antiretroviral therapy ( ART ) for adults initiating treatment in rural Ug and a. Design : Qualitative study , conducted with a pilot r and omized controlled trial . Methods : Sixty-two pilot intervention study participants took part in qualitative interviews on : preferences for content ; frequency and timing of SMS adherence reminders ; underst and ings and experiences of SMS reminders ; and underst and ings and experiences of real-time adherence monitoring . Analysis of interview data was inductive and derived categories describing how participants experienced the intervention , and what it meant to them . Results : SMS reminders prompted taking individual doses of antiretroviral therapy , and helped to develop a ‘ habit ’ of adherence . Real-time adherence monitoring was experienced as ‘ being seen ’ ; participants interpreted ‘ being seen ’ as an opportunity to demonstrate seriousness of commitment to treatment and ‘ taking responsibility ’ for adherence . Both SMS reminders and real-time monitoring were interpreted as signs of ‘ caring ’ by the healthcare system . Feeling ‘ cared about ’ offset depressed mood and invigorated adherence . Conclusion : Although serving as reminders , SMS messages and real-time adherence monitoring also had larger emotional and moral meanings for participants that they felt improved their adherence . Underst and ing the larger ‘ meanings in the messages , ’ as well as their more literal content and function , will be central in delineating how SMS reminders and other adherence interventions using cellular technology work or do not work in varying context Background . Suboptimal adherence to antiretroviral therapy ( ART ) is still pervasive . The effect of using a mobile phone call intervention to improve patient adherence is currently not known . Objective . This study aims to investigate the effects of a phone call intervention on adherence to ART and quality of life ( QOL ) of treatment-naive and treatment-experienced patients . Methods . A r and omized controlled trial was conducted in the three largest public hospitals . Adherence was measured by self-completed question naires . QOL was assessed by the WHOQOL-HIV BREF . Outcomes were assessed at day 15 , at 1 , 2 , and 3 months after start of treatment for treatment-naive patients and at 3 months after study enrollment for treatment-experienced patients . Results . A total of 103 treatment-naive and 93 treatment-experienced HIV/AIDS patients were consecutively recruited . Results show that a phone call intervention could maintain high self-reported adherence among both treatment-naive and treatment-experienced patients . After three months , significant QOL improvements were observed in domains of physical health ( P = 0.003 ) , level of independence ( P = 0.018 ) , environment ( P = 0.002 ) , and spirituality/religion/personal beliefs ( P = 0.021 ) among treatment-naive patients . Conclusion . A mobile phone call intervention to patients could maintain high adherence rates although no statistically significant differences were found . A phone call could improve some domains of QOL among treatment-naive patients Background Using two-way mobile phone text messages to improve adherence to antiretroviral medication enhances communication between patients and health workers . We describe the implication s of participants ’ responses to text messages in the Cameroon Mobile Phone SMS ( CAMPS ) trial . Findings This is a cross-sectional analysis of data from the intervention arm of the CAMPS trial . CAMPS was a r and omized controlled trial of motivational text messaging versus usual care to improve adherence to antiretroviral medication among people living with HIV in Yaounde , Cameroon ( n = 200 ) over a 6 month period . Participants in the intervention arm ( n = 101 ) were given a contact phone number , but were not required to respond to their reminder messages . If they did , their responses were noted and reported as counts and percentages . We received 99 phone calls and 55 text messages ( 154 responses ) from 48 participants during the study period . The median number of responses was 1 ( first quartile [ Q1 ] : 1 ; third quartile [ Q3 ] : 3 ) . Half ( n = 79 , 51.1 % ) of them were expressions of gratitude . The rest included requests for logistical ( n = 21 , 13.6 % ) , medical ( n = 20 , 12.9 % ) and financial ( n = 11 , 7.1 % ) support . Conclusion Initiating two-way mobile communication opens more channels for people living with HIV to express unmet needs . Research ers , policy makers and clinicians should be ready to respond to the needs expressed by patients who respond to text messages . Trial registration Pan-African Clinical Trials Registry : PACTR201011000261458 Clinical trials.gov : Background Mobile phone technology is a novel way of delivering health care and improving health outcomes . This trial investigates the use of motivational mobile phone text messages ( SMS ) to improve adherence to antiretroviral therapy ( ART ) over six months . Methodology /Principal Findings CAMPS was a single-site r and omized two-arm parallel design trial in Yaoundé , Cameroon . We enrolled and r and omized HIV-positive adults on ART , aged 21 years and above to receive a weekly st and ardized motivational text message versus usual care alone . The primary outcome was adherence measured using a visual analogue scale ( VAS ) , number of doses missed ( in the week preceding the interview ) and pharmacy refill data . Outcomes were measured at 3 and 6 months . Service providers and outcome assessors were blinded to allocation . Analysis was by intention-to-treat . Between November and December 2010 , 200 participants were r and omized , with 101 in the intervention group and 99 in the control group . At 6 months , overall retention was 81.5 % . We found no significant effect on adherence by VAS>95 % ( risk ratio [ RR ] 1.06 , 95 % confidence interval [ CI ] 0.89 , 1.29 ; p = 0.542 ; reported missed doses ( RR 1.01 , 95 % CI 0.87 , 1.16 ; p>0.999 ) or number of pharmacy refills ( mean difference [ MD ] 0.1 , 95 % CI : 0.23 , 0.43 ; p = 0.617 . One participant in the intervention arm reported a possible disclosure of status . Conclusions / Significance St and ardized motivational mobile phone text messages did not significantly improve adherence to ART in this study . Other types of messaging or longer term studies are recommended . Registration 1 . Pan-African Clinical Trials Registry ; PACTR201011000261458 2 . Clinical trials.gov ; Background Adequate antenatal care is important to both the health of a pregnant woman and her unborn baby . Given South Africa ’s high rate of cellphone penetration , mobile health interventions have been touted as a potentially powerful means to disseminate health information . This study aim ed to increase antenatal health knowledge and awareness by disseminating text messages about clinic procedures at antenatal visits , and how to be healthy during pregnancy . Methods Participants recruited were pregnant women attending a primary health care facility in Cape Town . A controlled clinical trial was carried out where the intervention group ( n = 102 ) received text messages staggered according to the week of pregnancy at the time of recruitment . The control group ( n = 104 ) received no text messages . These text messages contained antenatal health information , and were delivered in English , Xhosa or Afrikaans , according to the preference of each participant . A baseline knowledge question naire with nine questions was administered prior to the intervention . The same question naire was used with added health-related behaviour questions for the intervention group at exit . A modified intention-to-treat analysis was done . To compare the control and intervention group ’s knowledge , Fisher ’s exact tests and two- sample t-tests tests were carried out for binary and continuous outcomes , respectively . A focus group of seven participants from the intervention group was then conducted to gain more insight into how the text messages were perceived . Results There was substantial loss to follow-up during the study with only 57 % of the participants retained at exit . No statistically significant difference was detected between the control and intervention group in any of the nine knowledge questions at exit ( all p > 0.05 ) . Responses from the focus group indicated that the text messages acted as a welcome reminder and a source of positive motivation , and were perceived as extended care from the health care provider . Conclusions While the intervention failed to improve antenatal health knowledge , evidence from self-reported behaviour and the focus group suggests that text messages have the potential to motivate change in health-seeking behaviour . One should be mindful of loss to follow-up when rolling out mobile health interventions in developing country setting s . Trial registration Pan African Clinical Trials Registry PACTR201406000841188 . Registered 3 June 2014 Background Since the 2009 WHO and UNICEF recommendation that women receive home-based postnatal care within the first three days after birth , a growing number of low-income countries have explored integrating postnatal home visit interventions into their maternal and newborn health strategies . This r and omized trial evaluates a pilot program in which community health workers ( CHWs ) visit or call new mothers three days after delivery in peri-urban Kiambu County , Kenya . Methods Participants were individually r and omized to one of three groups : 1 ) early postnatal care three days after delivery provided in-person with a CHW using a simple checklist , 2 ) care provided by phone with a CHW using the same checklist , or 3 ) a st and ard of care group . Surveys were conducted ten days and nine weeks postnatal to measure outcomes related to compliance with referrals , self-reported health problems for mother and baby , care-seeking behaviors , and postnatal knowledge and practice s around the recognition of danger signs , feeding , nutrition , infant care and family planning . Results The home visit administration of the checklist increased the likelihood that women recognized postnatal problems for themselves and their babies and increased the likelihood that they sought care to address those problems identified for the child . In both the home visit and mobile phone implementation of the checklist , actions taken for postnatal problems happened earlier , particularly for infants . Knowledge was found to be high across all groups , with limited evidence that the checklist impacted knowledge and postnatal practice s around the recognition of danger signs , feeding , nutrition , infant care and family planning . Conclusion We find evidence that CHW-administered postnatal checklists can lead to better recognition of postnatal problems and more timely care-seeking . Furthermore , our results suggest that CHWs can affordably deliver many of the benefits of postnatal checklists . Trial registration Clinical Trials.gov NCT02104635 ; registered April 2 , 2014 Background . Antiretroviral medications are key for prevention of mother-to-child transmission ( PMTCT ) of HIV , and transmission mitigation is affected by service delivery , adherence , and retention . Methods . We conducted a cluster-r and omized controlled study in 26 facilities in Nyanza , Kenya , to determine the efficacy of SMS text messages on PMTCT outcomes . The relative risk and confidence intervals were estimated at the facility level using STATA . Results . 550 women were enrolled , from June 2012 to July 2013 . The median age was 25.6 years , and 85.3 % received ARVs . Maternal ARV use was similar between the intervention and control arms : 254/261 ( 97.3 % ) versus 241/242 ( 99.6 % ) at 34–36 weeks of gestation and 234/247 ( 94.7 % ) versus 229/229 ( 100 % ) at delivery . Among infants , 199/246 ( 80.9 % ) and 209/232 ( 90.1 % ) received ARVs ( RR : 0.91 ; 95 % CI : 0.77–1.14 ) ; 88 % versus 88.6 % were tested for HIV at 6 weeks , with 1/243 ( 0.4 % ) and 3/217 ( 1.4 % ) positive results in the intervention and control arms , respectively . Communication increased in both the intervention and control arms , with the mean number of 7.5 ( SD : 5.70 ) compared with 6 ( SD : 9.96 ) , p < 0.0001 . Conclusions . We identified high ARV uptake and infant HIV testing , with very low HIV transmission . Increased communication may influence health-seeking behaviors irrespective of technology . The long-term effectiveness of facilitated communication on PMTCT outcomes needs to be tested . The study has been registered on Clinical Trials.gov under the identifier NCT01645865 Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours . We aim ed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement , perceived usefulness , behavior change and program delivery preferences . Methods Mixed methods qualitative design combining four data sources ; ( i ) analytic data extracted directly from the software system , ( ii ) participant survey , ( iii ) focus groups to identify barriers and enablers to implementation and mechanisms of effect and ( iv ) recruitment screening logs and text message responses to examine engagement . This evaluation was conducted within the TEXT ME trial — a parallel design , single-blind r and omized controlled trial ( RCT ) of 710 patients with coronary heart disease ( CHD ) . Qualitative data were interpreted using inductive thematic analysis . Results 307/352 ( 87 % response rate ) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group . Factors increasing engagement included ( i ) ability to save and share messages , ( ii ) having the support of providers and family , ( iii ) a feeling of support through participation in the program , ( iv ) the program being initiated close to the time of a cardiovascular event , ( v ) personalization of the messages , ( vi ) opportunity for initial face-to-face contact with a provider and ( vii ) that program and content was perceived to be from a credible source . Clear themes relating to program delivery were that diet and physical activity messages were most valued , four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer . Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aim ed at improving health-related behavior . The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling . Trial Registration Australia and New Zeal and Clinical Trials Registry , ACTRN12611000161921 Introduction The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended . Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels , followed by linkage to treatment or prevention . As effective linkage strategies are identified , it becomes important to underst and how these strategies work . We use qualitative data from The Linkages Study , a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa , to show how lay counsellor home HIV testing and counselling ( home HTC ) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services . Methods We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe , Sheema District , Ug and a. The participant sample included both HIV+ men and women ( N=47 ) and HIV-uncircumcised men ( N=52 ) . Interview and focus group audio-recordings were translated and transcribed . Each transcript was summarized . The summaries were analyzed inductively to identify emergent themes . Thematic concepts were grouped to develop general constructs and framing propositional statements . Results Trial participants expressed interest in linking to clinic-based services at testing , but faced obstacles that eroded their initial enthusiasm . Follow-up support by lay counsellors intervened to restore interest and inspire action . Together , home HTC and follow-up support improved morale , created a desire to reciprocate , and provided reassurance that services were trustworthy . In different ways , these functions built links to the health service system . They worked to strengthen individuals ’ general sense of capability , while making the idea of accessing services more manageable and familiar , thus reducing linkage barriers . Conclusions Home HTC with follow-up support leads to linkage by building “ social bridges , ” interpersonal connections established and developed through repeated face-to-face contact between counsellors and prospect i ve users of HIV treatment and male circumcision services . Social bridges link communities to the service system , inspiring individuals to overcome obstacles and access care Background This trial aims at testing the efficacy of weekly reminder and motivational text messages , compared to usual care in improving adherence to Highly Active Antiretroviral Treatment in patients attending a clinic in Yaoundé , Cameroon . Methods and Design This is a single-centered r and omized controlled single-blinded trial . A central computer generated r and omization list will be generated using r and om block sizes . Allocation will be determined by sequentially numbered sealed opaque envelopes . 198 participants will either receive the mobile phone text message or usual care . Our hypothesis is that weekly motivational text messages can improve adherence to Highly Active Antiretroviral Treatment and other clinical outcomes in the control group by acting as a reminder , a cue to action and opening communication channels . Data will be collected at baseline , three months and six months . A blinded program secretary will send out text messages and record delivery . Our primary outcomes are adherence measured by the visual analogue scale , self report , and pharmacy refill data . Our secondary outcomes are clinical : weight , body mass index , opportunistic infections , all cause mortality and retention ; biological : Cluster Design ation 4 count and viral load ; and quality of life . Analysis will be by intention-to-treat . Covariates and subgroups will be taken into account . Discussion This trial investigates the potential of SMS motivational reminders to improve adherence to Highly Active Antiretroviral Treatment in Cameroon . The intervention targets non-adherence due to forgetfulness and other forms of non-adherence . Trial Registration Pan-African Clinical Trials Registry PACTR201011000261458http:// clinical Introduction : Zambia has high HIV prevalence and low voluntary medical male circumcision ( VMMC ) rates , heightening the need for effective VMMC dem and generation strategies for HIV prevention . Methods : A 3-arm r and omized controlled trial measured the impact of 2 short message service ( SMS ) campaigns on self-reported and verified VMMC uptake over 6 months in Lusaka Province . The study enrolled 2312 uncircumcised males aged 15–30 previously subscribed on Zambia U-Report , an existing SMS platform providing confidential , free counseling services relevant to HIV and other sexually transmitted infections . Participants in the “ Conventional ” campaign group received a st and ard package of messages promoting VMMC . Messages sent to the “ Tailored ” campaign group were targeted at participants ' intention level to get circumcised . The control group had routine counselor access through SMS . Data were collected using SMS surveys , and verification of self-reported VMMC uptake used health facility client data . Results : Six-month self-reported VMMC uptake was 11.6 % , 12.6 % , and 10.4 % in the Conventional , Tailored , and control arms , respectively ; verified uptake was 1.8 % , 1.1 % , and 1.5 % . Using multivariate logistic regression , the adjusted odds ratio of self-reported VMMC uptake was 1.17 ( 95 % CI : 0.80 to 1.72 ) in the Conventional campaign arm compared with the control arm and 1.24 ( 95 % CI : 0.84 to 1.81 ) in the Tailored campaign arm . The adjusted odds ratios of verified VMMC uptake in the Conventional and Tailored campaign arms were 1.34 ( 95 % CI : 0.45 to 4.02 ) and 0.67 ( 95 % CI : 0.20 to 2.23 ) , respectively . Conclusions : Neither SMS campaign had statistically significant impact on VMMC uptake compared with routine SMS counseling . Future research is necessary to fully underst and the potential of SMS-based tools for VMMC dem and creation Background Providing women with contraceptive methods following abortion is important to reduce repeat abortion rates , yet evidence for effective post-abortion family planning interventions are limited . This protocol outlines the evaluation of a mobile phone-based intervention using voice messages to support post-abortion family planning in Cambodia . Methods / Design A single blind r and omised controlled trial of 500 participants . Clients aged 18 or over , attending for abortion at four Marie Stopes International clinics in Cambodia , owning a mobile phone and not wishing to have a child at the current time are r and omised to the mobile phone-based intervention or control ( st and ard care ) with a 1:1 allocation ratio . The intervention comprises a series of six automated voice messages to remind clients about available family planning methods and provide a conduit for additional support . Clients can respond to message prompts to request a phone call from a counsellor , or alternatively to state they have no problems . Clients requesting to talk to a counsellor , or who do not respond to the message prompts , receive a call from a Marie Stopes International Cambodia counsellor who provides individualised advice and support regarding family planning . The duration of the intervention is 3 months . The control group receive existing st and ard of care without the additional mobile phone-based support . We hypothesise that the intervention will remind clients about contraceptive methods available , identify problems with side effects early and provide support , and therefore increase use of post-abortion family planning , while reducing discontinuation and unsafe method switching . Participants are assessed at baseline and at 4 months . The primary outcome measure is use of an effective modern contraceptive method at 4 months post abortion . Secondary outcome measures include contraception use , pregnancy and repeat abortion over the 4-month post-abortion period . Risk ratios will be used as the measure of effect of the intervention on the outcomes , and these will be estimated with 95 % confidence intervals . All analyses will be based on the ‘ intention to treat ’ principle . Discussion This study will provide evidence on the effectiveness of a mobile phone-based intervention using voice messages to support contraception use in a population with limited literacy . Findings could be generalisable to similar population s in different setting s . Trial registration Clinical Trials.gov Identifier : Background . Low-income mothers have greater challenges in accessing health care services due changes in the health care system and budget cuts . The purpose of this r and omized clinical trial was to test a nurse practitioner ( NP ) intervention using cell phone and texting on maternal/infant outcomes . Methods . The sample included 129 mother-infant pairs . Intervention group mothers received NP 2-way cell phone follow-up intervention post – hospital discharge for 6 months . Results . Intervention mothers ’ perceived social support was significantly higher . Intervention infants received their first newborn follow-up visit significantly earlier ( 6 vs 9 days ) ; significantly more infants were immunized at recommended times ( 2 , 4 , and 6 months of age ) ; and there were fewer infant morbidities compared to controls . The intervention saved between $ 51 030 and $ 104 277 in health care costs averted . Conclusion . This easy-to-use , safe intervention is an effective way to reach a wide range of population s and demonstrated improved maternal/infant outcomes and decreased cost SMS is a widely used technology globally and may also improve ART adherence , yet SMS notifications to social supporters following real-time detection of missed doses showed no clear benefit in a recent pilot trial . We examine the demographic and social-cultural dynamics that may explain this finding . In the trial , 63 HIV-positive individuals initiating ART received a real-time adherence monitor and were r and omized to two types of SMS reminder interventions versus a control ( no SMS ) . SMS notifications were also sent to 45 patient-identified social supporters for sustained adherence lapses . Like participants , social supporters were interviewed at enrollment , following their matched participant ’s adherence lapse and at exit . Social supporters with regular income ( RR = 0.27 , P = 0.001 ) were significantly associated with fewer adherence lapses . Instrumental support was associated with fewer adherence lapses only among social supporters who were food secure ( RR = 0.58 , P = 0.003 ) . Qualitative interview data revealed diverse and complex economic and relationship dynamics , affecting social support . Re source availability in emotionally positive relationships seemingly facilitated helpful support , while limited re sources prevented active provision of support for many . Effective social support appeared subject to social supporters ’ food security , economic stability and a well-functioning social network dependent on trust and supportive disclosure Aim The aim of this study was to examine the acceptability and efficacy of interactive short message service ( SMS ) in improving medication adherence in antiretroviral treatment (ART)-naïve individuals living with HIV/AIDS in Hengyang , Hunan , China . Background SMS via mobile phone has emerged as a potential tool for improving ART adherence . However , most studies used SMS only as a medication reminder , with few studies exploring the effect of comprehensive , interactive SMS . Patients and methods In a r and omized controlled trial , 100 HIV-positive patients on ART for <3 months were r and omized into control or intervention arm . Participants in the control group received routine st and ard instruction for ART medication in the HIV clinics , while the intervention group received 6 months of an SMS intervention in addition to the st and ard care . A total of 124 text messages within 6 modules were edited , preinstalled , and sent to participants according to personalized schedules . Knowledge ( of HIV and HIV medications ) , self-reported antiretroviral adherence ( Visual Analog Scale [ VAS ] and Community Programs for Clinical Research on AIDS [ CPCRA ] Antiretroviral Medication Self-Report ) , and CD4 count were assessed at baseline and immediate post-intervention . Intervention participants were interviewed after completion of the study about their satisfaction with and acceptability of the SMS intervention . Results Baseline assessment s were comparable between arms . Repeated- measures analysis showed that both HIV-related and ART medication knowledge of the intervention group showed better improvement over time than those of the control group after the intervention ( P<0.0001 ) . For the adherence measures , compared with the control group , participants in the intervention group had significantly higher VAS mean score ( Z=2.735 , P=0.006 ) and lower suboptimal adherence rate ( Z=2.208 , P=0.027 ) at the end of the study . The intervention had no effect on CD4 cell count . Almost all ( 96 % ) intervention participants reported satisfaction or high satisfaction with the SMS intervention , with 74 % desiring to continue to receive the SMS intervention . The preferred frequency of messages was 1–2 messages per week . Conclusion An interactive SMS intervention with comprehensive content shows promising efficacy in promoting medication adherence in ART-naïve individuals . Future work might further refine its ability to optimally tailor the intervention for individual preferences Background Mobile phones are increasingly used in health systems in developing countries and innovative technical solutions have great potential to overcome barriers of access to reproductive and child health care . However , despite widespread support for the use of mobile health technologies , evidence for its role in health care is sparse . Objective We aim ed to evaluate the association between a mobile phone intervention and perinatal mortality in a re source -limited setting . Methods This study was a pragmatic , cluster-r and omized , controlled trial with primary health care facilities in Zanzibar as the unit of r and omization . At their first antenatal care visit , 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary health care facilities were included in this study and followed until 42 days after delivery . Twenty-four primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text message and voucher component . Secondary outcome measures included stillbirth , perinatal mortality , and death of a child within 42 days after birth as a proxy of neonatal mortality . Results Within the first 42 days of life , 2482 children were born alive , 54 were stillborn , and 36 died . The overall perinatal mortality rate in the study was 27 per 1000 total births . The rate was lower in the intervention clusters , 19 per 1000 births , than in the control clusters , 36 per 1000 births . The intervention was associated with a significant reduction in perinatal mortality with an odds ratio ( OR ) of 0.50 ( 95 % CI 0.27 - 0.93 ) . Other secondary outcomes showed an insignificant reduction in stillbirth ( OR 0.65 , 95 % CI 0.34 - 1.24 ) and an insignificant reduction in death within the first 42 days of life ( OR 0.79 , 95 % CI 0.36 - 1.74 ) . Conclusions Mobile phone applications may contribute to improved health of the newborn and should be considered by policy makers in re source -limited setting s. Trial Registration Clinical Trials.gov NCT01821222 ; http://www . clinical trials.gov/ct2/show/NCT01821222 ( Archived by WebCite at http://www.webcitation.org/6NqxnxYn0 ) OBJECTIVES We examined whether and how an HIV prevention diffusion-based intervention spread throughout participants ' online social networks and whether changes in social network ties were associated with increased HIV prevention and testing behaviors . METHODS We r and omly assigned 112 primarily racial/ethnic minority men who have sex with men ( MSM ) to receive peer-delivered HIV ( intervention ) or general health ( control ) information over 12 weeks through closed Facebook groups . We recorded participants ' public Facebook friend networks at baseline ( September 2010 ) and follow-up ( February 2011 ) , and assessed whether changes in network growth were associated with changes in health engagement and HIV testing . RESULTS Within-group ties increased in both conditions from baseline to follow-up . Among the intervention group , we found a significant positive relation between increased network ties and using social media to discuss sexual behaviors . We found a positive trending relationship between increased network ties and likelihood of HIV testing , follow-up for test results , and participation in online community discussion s. No significant differences were seen within control groups . CONCLUSIONS Among high-risk MSM , peer-led social media HIV prevention interventions can increase community cohesion . These changes appear to be associated with increased HIV prevention and testing behaviors Immunization coverage of vulnerable children is often sub-optimal in many low- and middle-income countries . The use of a reminder/recall ( R/R ) system has been one of the strategies shown to be effective in improving immunization rates . In the resent study , we evaluated the effect of R/R and Primary Health Care Immunization Providers ’ Training ( PHCIPT ) intervention on routine immunization completion among 595 infants in Ibadan , Nigeria . The design was a group r and omized controlled trial with Local Government Area ( LGA ) being the unit of r and omization . Four r and omly selected LGAs were r and omized to receive a cellphone R/R only ( A ) , a PHCIPT only ( B ) ; combined R/R and PHCIPT ( C ) intervention or serve as a control group ( D ) . Children aged 0–12 weeks were consecutively recruited into each group and followed up for 12 months . The primary outcome measure was routine immunization completion at 12 months of age . At the study endpoint , immunization completion rates were : group A , 98.6 % ; group B , 70 % ; group C , 97.3 % ; and group D , 57.3 % . Compared to the control group , the cellphone R/R group was 72 % ( RR 1.72 , 95 % CI 1.50–1.98 ) and the combined RR/PHCIPT group 70 % ( RR 1.70 , 95 % CI 1.47–1.95 ) more likely to complete immunization . In contrast , immunization completion in the PHCIPT group was marginally different from the control group ( RR 1.22 , 95 % CI 1.03–1.45 ) . These findings remained robust to adjustment for potential predictors of immunization completion as covariates . In conclusion , cellphone reminder/recall was effective in improving immunization completion in this Nigerian setting . Its use is recommended for large scale implementation ABSTRACT Urban adolescents face economic , social , and behavioral challenges in adhering to long-term contraceptive use . Use of text messaging reminders has the potential to increase adherence to family planning appointments and to educate patients about safe sexual health practice s ; however , nonresponsiveness to messages is difficult to interpret and may jeopardize programmatic success . We aim ed to underst and why adolescent girls enrolled in a r and omized , controlled pilot trial ( DepoText ) design ed to increase attendance at family planning visits were periodically nonresponsive to text messages through conducting structured interviews with participants whose text reply rates were less than 100 % during the trial period . Qualitative and quantitative data were collected and classified using descriptive data analysis . Reasons for nonresponsiveness , barriers to continuous cell phone coverage , cell phone plan characteristics , and attitudes toward the DepoText program were the primary endpoints of interest . Most participants ( 78 % ) attributed instances of nonresponsiveness to being away from the phone or due to a personal conflict such as school or work . Service interruption due to bill nonpayment ( 44 % ) , phone loss ( 28 % ) , and cell phone number change ( 28 % ) were significant barriers to continuous coverage during the trial period , and many respondents indicated that the downturn in the economy made it more difficult to maintain their cell phone plan . Almost a third reported having to choose between cell phone and other payments , but the vast majority ( 88 % ) considered their cell phone a “ need ” rather than a “ want . ” Participants universally expressed satisfaction with the text messaging program and reported feeling more connected to the clinic ( 96 % ) through the messages serving as reminders ( 64 % ) , encouragement to assume personal responsibility for their health care ( 12 % ) , and enhanced personal connection with the clinic staff ( 4 % ) . Our study suggests that a text messaging program can be used in an urban clinical setting to communicate with adolescent girls about family planning services . While economic barriers to continuous cell phone coverage do exist , adolescents indicate that the text message reminder system can be a valuable tool for enhancing clinic connectedness and promoting autonomy in care-seeking behavior Background Globally , vaccine preventable diseases are responsible for nearly 20 % of deaths annually among children < 5 years old . Worldwide , many children dropout from the vaccination program , are vaccinated late , or incompletely vaccinated . We evaluated the impact of text messaging and sticker reminders to reduce dropouts from the vaccination program . Methods The evaluation was conducted in three selected districts in Kenya : Machakos , Langata and Njoro . Three health facilities were selected in each district , and r and omly allocated to send text messages or provide stickers reminding parents to bring their children for second and third dose of pentavalent vaccine , or to the control group ( routine reminder ) with next appointment date indicated on the well-child booklet . Children aged < 12 months presenting for their first dose of pentavalent vaccine were enrolled . A dropout was defined as not returning for vaccination ≥2 weeks after scheduled date for third dose of pentavalent vaccine . We calculated dropout rate as a percentage of the difference between first and third pentavalent dose . Results We enrolled 1,116 children ; 372 in each intervention and 372 controls between February and October 2014 . Median age was 45 days old ( range : 31–99 days ) , and 574 ( 51 % ) were male . There were 136 ( 12 % ) dropouts . Thirteen ( 4 % ) children dropped out among those who received text messages , 60 ( 16 % ) among who received sticker reminders , and 63 ( 17 % ) among the controls . Having a caregiver with below secondary education [ Odds Ratio ( OR ) 1.8 , 95 % Confidence Interval ( CI ) 1.1–3.2 ] , and residing > 5 km from health facility ( OR 1.6 , CI 1.0–2.7 ) were associated with higher odds of dropping out . Those who received text messages were less likely to drop out compared to controls ( OR 0.2 , CI 0.04–0.8 ) . There was no statistical difference between those who received stickers and controls ( OR 0.9 , CI 0.5–1.6 ) . Conclusion Text message reminders can reduce vaccination dropout rates in Kenya . We recommend the extended implementation of text message reminders in routine vaccination services OBJECTIVE To assess whether a warning system based on mobile SMS messages increases the adherence of HIV-infected Brazilian women to antiretroviral drug-based treatment regimens and their impressions and satisfaction with respect to incoming messages . DESIGN A r and omized controlled trial was conducted from May 2009 to April 2010 with HIV-infected Brazilian women . All participants ( n=21 ) had a monthly multidisciplinary attendance ; each participant was followed over a 4-month period , when adherence measures were obtained . Participants in the intervention group ( n=8 ) received SMS messages 30 min before their last scheduled time for a dose of medicine during the day . The messages were sent every Saturday and Sunday and on alternate days during the working week . Participants in the control group ( n=13 ) did not receive messages . MEASUREMENTS Self-reported adherence , pill counting , microelectronic monitors ( MEMS ) and an interview about the impressions and satisfaction with respect to incoming messages . RESULTS The HIV Alert System ( HIVAS ) was developed over 7 months during 2008 and 2009 . After the study period , self-reported adherence indicated that 11 participants ( 84.62 % ) remained compliant in the control group ( adherence exceeding 95 % ) , whereas all 8 participants in the intervention group ( 100.00 % ) remained compliant . In contrast , the counting pills method indicated that the number of compliant participants was 5 ( 38.46 % ) for the control group and 4 ( 50.00 % ) for the intervention group . Microelectronic monitoring indicated that 6 participants in the control group ( 46.15 % ) were adherent during the entire 4-month period compared to 6 participants in the intervention group ( 75.00 % ) . According to the feedback of the 8 participants who completed the research in the intervention group , along with the feedback of 3 patients who received SMS for less than 4 months , that is , did not complete the study , 9 ( 81.81 % ) believed that the SMS messages aided them in treatment adherence , and 10 ( 90.90 % ) responded that they would like to continue receiving SMS messages . CONCLUSION SMS messaging can help Brazilian women living with HIV/AIDS to adhere to antiretroviral therapy for a period of at least 4 months . In general , the results are encouraging because the SMS messages stimulated more participants in the intervention group to be adherent to their treatment , and the patients were satisfied with the messages received , which were seen as reminders , incentives and signs of affection by the health clinic for a marginalized population BACKGROUND Mobile ( cell ) phone communication has been suggested as a method to improve delivery of health services . However , data on the effects of mobile health technology on patient outcomes in re source -limited setting s are limited . We aim ed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load . METHODS WelTel Kenya1 was a multisite r and omised clinical trial of HIV-infected adults initiating antiretroviral therapy ( ART ) in three clinics in Kenya . Patients were r and omised ( 1:1 ) by simple r and omisation with a r and om number generating program to a mobile phone short message service ( SMS ) intervention or st and ard care . Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. R and omisation , laboratory assays , and analyses were done by investigators masked to treatment allocation ; however , study participants and clinic staff were not masked to treatment . Primary outcomes were self-reported ART adherence ( > 95 % of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits ) and plasma HIV-1 viral RNA load suppression ( < 400 copies per mL ) at 12 months . The primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , NCT00830622 . FINDINGS Between May , 2007 , and October , 2008 , we r and omly assigned 538 participants to the SMS intervention ( n=273 ) or to st and ard care ( n=265 ) . Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group ( relative risk [ RR ] for non-adherence 0·81 , 95 % CI 0·69 - 0·94 ; p=0·006 ) . Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group , ( RR for virologic failure 0·84 , 95 % CI 0·71 - 0·99 ; p=0·04 ) . The number needed to treat ( NNT ) to achieve greater than 95 % adherence was nine ( 95 % CI 5·0 - 29·5 ) and the NNT to achieve viral load suppression was 11 ( 5·8 - 227·3 ) . INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals . Mobile phones might be effective tools to improve patient outcome in re source -limited setting s. FUNDING US President 's Emergency Plan for AIDS Relief Objectives : In many African setting s , MSM are a stigmatized group whose access to and engagement in HIV care may be challenging . Our aim was to design a targeted , culturally appropriate intervention to promote care engagement and antiretroviral therapy ( ART ) adherence for MSM in coastal Kenya , and describe intervention safety , feasibility , and acceptability based upon a small pilot study . Design : Based on qualitative work including in-depth interviews with HIV-positive MSM and focus groups with providers , we developed a tailored intervention and conducted a pilot test to refine intervention material s and procedures . Methods : The Shikamana intervention combines modified Next-Step Counseling by trained providers , support from a trained peer navigator , and tailored use of SMS messaging , phone calls , and discrete pill carriers . Providers , including counselors and clinicians , work together with peer navigators as a case management team . Results : Forty HIV-positive MSM aged 19–51 participated in intervention development and testing . Six counselors , three clinical officers , and four MSM peers were trained in intervention procedures . Of 10 ART-naïve participants who enrolled in the pilot , eight completed follow-up with no adverse events reported . One participant was lost to follow-up after 2 months and another failed to initiate ART despite ongoing counseling . No adverse events were reported . Staff feedback and exit interviews rated the intervention as feasible and acceptable . Conclusion : This adherence support intervention tailored for Kenyan MSM was well tolerated , feasible , and acceptable in the pilot phase . A r and omized controlled trial of a scaled-up programme to estimate intervention efficacy is ongoing OBJECTIVE To pilot test the Text Reminders for Immunization Compliance in Kids ( TRICKs ) program to evaluate its feasibility and potential to increase immunization coverage . DESIGN R and omized controlled trial ( RCT ) . SETTING Pediatric clinic . PARTICIPANTS Parents of newborns being discharged from a local hospital who intended to seek child health care at the University-sponsored pediatric resident and faculty clinic . INTERVENTION Text message immunization reminders prior to immunization due date s. MAIN OUTCOME MEASURES Receipt and timeliness of immunizations at 2 , 4 and 6 months of age . RESULTS Participants ( N=90 ) were English ( 83 % ) or Spanish ( 17 % ) speaking . The majority were female ( 83 % ) , on public insurance ( 59 % ) , and had adequate health literacy ( 96 % ) . Parents were married or a member of an unmarried couple ( 62 % ) . Over 66 % had a high school diploma or less . Greater numbers of intervention children received immunizations and were " on time " using per protocol analysis ; though not statistically significance . Limitations include sample size , problematic text messaging software , and loss of phone service at 7 months for 40 % of intervention parents . However , post-intervention interviews ( N=18 ) indicated strong support for TRICKs ; 83 % found the text message reminders very helpful and 17 % somewhat helpful . DISCUSSION Pilot testing allowed us to assess processes , including recruitment , retention , and software , which will increase the success of an RCT . Software with built-in backup systems is needed for follow-up when mobile service is interrupted . However , in spite of limitations , immunization rates were higher in the text message reminder group , though not statistically significant . Parent support and interest was high . A fully powered RCT is needed with follow-up over the full 4 - 3 - 1 - 3 - 3 - 1 series . Based on our results , for 80 % power where we expected 90 % compliance in the intervention group and 80 % in the control group we need 219 per group , plus increases to address drop out and loss of follow-up OBJECTIVES To consider whether Youth All Engaged ! ( a text message intervention ) intensified the effects of the adolescent pregnancy prevention Teen Outreach Program ( control ) for youths . METHODS In this trial performed in Denver , Colorado , from 2011 to 2014 , we r and omized 8 Boys & Girls Clubs each of 4 years into 32 clubs per year combinations to ensure each club would serve as a treatment site for 2 years and a control site for 2 years . Control intervention consisted of the Teen Outreach Program only . We enrolled 852 youths ( aged 14 - 18 years ) , and 632 were retained at follow-up , with analytic sample s ranging from 50 to 624 across outcomes . We examined program costs , and whether the intervention increased condom and contraceptive use , access to care , and pregnancy prevention . RESULTS Control program costs were $ 1184 per participant , and intervention costs were an additional $ 126 per participant ( + 10.6 % ) . There were no statistically significant differences in primary outcomes for the full sample . Hispanic participants in the intervention condition had fewer pregnancies at follow-up ( 1.79 % ) than did those in the control group ( 6.72 % ; P = .02 ) . CONCLUSIONS Youth All Engaged is feasible , low cost , and could have potential benefits for Hispanic youths ABSTRACT In Thail and , young men who have sex with men ( YMSM ) and transgender women ( TG ) are disproportionately affected by HIV and have suboptimal care continuum outcomes . Although Thai YMSM and young TG are early adopters of emerging technologies and have high Internet and technology access and utilization , the potential of technology has not been harnessed to optimize the HIV treatment cascade . We interviewed 18 behaviorally HIV-infected YMSM and young TG regarding care challenges , identified how eHealth could address care needs , and elicited preferences for eHealth interventions . Participants reported struggling with individual and societal-level stigma which negatively impacted linkage to and retention in care , and antiretroviral therapy adherence . YMSM and young TG described inadequate in-person support services and heavily relied on r and om online re sources to fill information and support gaps , but sometimes viewed them as untrustworthy or inconsistent . Participants universally endorsed the development of eHealth re sources and proposed how they could ameliorate individual-level fears over stigma and improve public perceptions about HIV . Personalized and integrated eHealth interventions with interactive , user-driven structures , credible content , rewards for engagement , real-time counseling and reminder support could help overcome barriers YMSM and young TG face in traditional HIV healthcare systems and have the potential to improve care outcomes This study reports the RCT findings of G2 G , the first mobile health HIV prevention program for 14- to 18-year-old sexual minority males tested nationally . BACKGROUND : Guy2Guy ( G2 G ) is the first comprehensive HIV prevention program developed for sexual minority males as young as 14 years old and is delivered nationally via text messaging . Here , we report the results of the pilot r and omized control trial . METHODS : G2 G was tested against an attention-matched “ healthy lifestyle ” control ( eg , self-esteem ) . Both programs lasted 5 weeks and delivered 5 to 10 text messages daily . A 1-week booster was delivered 6 weeks subsequently . Participants were cisgender males ages 14 to 18 years old who were gay , bisexual , and /or queer and had an unlimited text messaging plan . Youth were recruited across the United States via Facebook and enrolled by telephone from October 2014 to April 2015 . Ninety-day postintervention outcomes were condomless sex acts ( CSA ) and abstinence and , secondarily , HIV testing . We also examined these outcomes at intervention end and stratified them by sexual experience . RESULTS : At 90 days postintervention , there were no significant differences in CSAs or abstinence noted . Among participants who were sexually active at baseline , intervention participants were significantly more likely to report getting an HIV test ( adjusted odds ratio = 3.42 , P = .001 ) . They were also less likely than control youth to be abstinent ( adjusted odds ratio = 0.48 , P = .05 ) . CSAs were significantly lower for those in the intervention versus control at intervention end ( incident rate ratio = 0.39 , P = .04 ) , although significance was lost once age was added to the analysis ( incident rate ratio = 0.58 , P = .26 ) . CONCLUSIONS : G2 G appears promising in increasing adolescent HIV testing rates . Sex-positive intervention messages appear to have increased the participants ’ comfort with having sex ( ie , less abstinence ) while not increasing their potential for HIV transmission ( ie , more CSAs ) . Additional content or features may be needed to invigorate condom use A r and omized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention ( iSTEP ) design ed to increase physical activity ( PA ) and improve neurocognitive functioning among HIV-positive persons . This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population , including assessment of PA barriers and facilitators . Two focus groups , with 9 and 12 unique HIV-positive individuals , respectively , were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA . Group discussion s revealed prominent PA barriers , including HIV symptoms ( neuropathy , lipoatrophy ) , antiretroviral medication effects , and fatigue ; significant PA facilitators included self-monitoring and family support . Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities . These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders Background Maternal attendance at postnatal clinic visits and timely diagnosis of infant HIV infection are important steps for prevention of mother-to-child transmission ( PMTCT ) of HIV . We aim ed to use theory-informed methods to develop text messages targeted at facilitating these steps . Methods We conducted five focus group discussion s with health workers and women attending antenatal , postnatal , and PMTCT clinics to explore aspects of women 's engagement in postnatal HIV care and infant testing . Discussion topics were informed by constructs of the Health Belief Model ( HBM ) and prior empirical research . Qualitative data were coded and analyzed according to the construct of the HBM to which they related . Themes were extracted and used to draft intervention messages . We carried out two stages of further messaging development : messages were presented in a follow-up focus group in order to develop optimal phrasing in local language s. We then further refined the messages , pretested them in individual cognitive interviews with selected health workers , and finalized the messages for the intervention . Results Findings indicated that brief , personalized , caring , polite , encouraging , and educational text messages would facilitate women bringing their children to clinic after delivery , suggesting that text messages may serve as an important “ cue to action . ” Participants emphasized that messages should not mention HIV due to fear of HIV testing and disclosure . Participants also noted that text messages could capitalize on women 's motivation to attend clinic for childhood immunizations . Conclusions Applying a multi-stage content development approach to crafting text messages – informed by behavioral theory – result ed in message content that was consistent across different focus groups . This approach could help answer “ why ” and “ how ” text messaging may be a useful tool to support maternal and child health . We are evaluating the effect of these messages on improving postpartum PMTCT retention and infant HIV testing in a r and omized trial OBJECTIVES To evaluate whether text-messaging programs can improve reproductive health among adolescent girls in low- and middle-income countries . METHODS We conducted a cluster-r and omized controlled trial among 756 female students aged 14 to 24 years in Accra , Ghana , in 2014 . We r and omized 38 schools to unidirectional intervention ( n = 12 ) , interactive intervention ( n = 12 ) , and control ( n = 14 ) . The unidirectional intervention sent participants text messages with reproductive health information . The interactive intervention engaged adolescents in text-messaging reproductive health quizzes . The primary study outcome was reproductive health knowledge at 3 and 15 months . Additional outcomes included self-reported pregnancy and sexual behavior . Analysis was by intent-to-treat . RESULTS From baseline to 3 months , the unidirectional intervention increased knowledge by 11 percentage points ( 95 % confidence interval [ CI ] = 7 , 15 ) and the interactive intervention by 24 percentage points ( 95 % CI = 19 , 28 ) , from a control baseline of 26 % . Although we found no changes in reproductive health outcomes overall , both unidirectional ( odds ratio [ OR ] = 0.14 ; 95 % CI = 0.03 , 0.71 ) and interactive interventions ( OR = 0.15 ; 95 % CI = 0.03 , 0.86 ) lowered odds of self-reported pregnancy for sexually active participants . CONCLUSIONS Text-messaging programs can lead to large improvements in reproductive health knowledge and have the potential to lower pregnancy risk for sexually active adolescent girls This two-phase pilot study aim ed to design , pilot , and refine an automated interactive voice response ( IVR ) intervention to support antiretroviral adherence for people living with HIV ( PLH ) , in Kolkata , India . Mixed- methods formative research included a community advisory board for IVR message development , 1-month pre-post pilot , post-pilot focus groups , and further message development . Two IVR calls are made daily , timed to patients ’ dosing schedules , with brief messages ( < 1-min ) on strategies for self-management of three domains : medical ( adherence , symptoms , co-infections ) , mental health ( social support , stress , positive cognitions ) , and nutrition and hygiene ( per PLH preferences ) . Three ART appointment reminders are also sent each month . One-month pilot results ( n = 46 , 80 % women , 60 % sex workers ) found significant increases in self-reported ART adherence , both within past three days ( p = 0.05 ) and time since missed last dose ( p = 0.015 ) . Depression was common . Messaging content and assessment domains were exp and ed for testing in a r and omized trial currently underway Mobile phones have been shown effective in several public health domains . However , there are few evaluations of the effectiveness of mobile health in health promotion . Also , although many studies have referenced behavioral theory , none appears to have explicitly tested theoretical assumptions or demonstrated mechanisms of change . More robust evaluation models that incorporate theory and measurement of behavioral mediators are needed . As in all public health programs , mobile health operates within a social ecological context . For example , organizational- and individual-level programs seek to influence health and health care practice s and individual health behaviors . New programs such as Text4baby demonstrate how theory and explicit testing of mediators can be incorporated in evaluations . There are challenges and opportunities facing mHealth evaluations given the nature of the mobile channel . Mobile communication is ubiquitous , available at all times and places , and thus experimental control is often difficult . Natural experiments using variation in dosage of mHealth and place- or location-based design s may increase experimental control . Text4baby is a text messaging program that provides prenatal care messages to pregnant women and new mothers . It uses a partnership model with health care facilities often serving as local implementation partners . The authors review a case example of the evaluation of Text4baby at Madigan Army Medical Center . Participants were r and omized to usual prenatal care plus text messaging or usual care alone . The evaluation has a theoretical model of behavior change and measures mediators as well as behavioral outcomes . Results will inform how behavioral theory works within mobile health programs BACKGROUND Extensive uptake of mobile phones offers an unprecedented opportunity to improve global healthcare delivery , especially among underserved population s. Mobile health ( mHealth ) has been increasingly recognized as a promising approach to addressing challenges in global maternal-child health and may play an important role in accelerating progress towards improved outcomes . However , more evidence guiding development of mHealth interventions is needed . The current study explores factors that may support or hinder adoption and use of a proposed mHealth intervention to improve caregiver home management of common childhood illnesses in order to shape program development . METHODS Elicitation interviews were conducted with a convenience sample of 25 mothers recruited from a larger cluster-r and omized survey sample in the Cono Norte region of Arequipa , Peru . Interview data were analyzed in Spanish to preserve important cultural nuances . RESULTS Thematic analysis revealed potential facilitators of and barriers to uptake of the proposed mHealth program . Potential facilitators of caregiver participation include opportunity to engage in two-way communication with healthcare providers , development of instrumental and support knowledge to care for sick children , and healthcare challenges faced in a re source -poor community . Potential barriers include preference for in-person healthcare visits , program cost , text messaging abilities , and concern around program legitimacy . CONCLUSIONS This study underscores the potential for mHealth to improve global healthcare delivery in the area of maternal-child health . It demonstrates that mHealth interventions can meet the needs of vulnerable population s by offering novel approaches to promoting evidence -based care . This in-depth underst and ing of factors that may influence participation and use of this proposed mHealth program will help shape development of the intervention in this community Objective : Many sub-Saharan African countries report high postpartum loss to follow-up of mother – baby pairs . We aim ed to determine whether interactive text messages improved rates of clinic attendance and early infant HIV testing in the Nyanza region of Kenya . Design : Parallel-group , unblinded , r and omized controlled trial . Methods : HIV-positive pregnant women at least 18 years old and enrolled in the prevention of mother-to-child transmission of HIV programme were r and omized to receive either text messages ( SMS group , n = 195 ) or usual care ( n = 193 ) . Messages were developed using formative focus group research informed by constructs of the Health Belief Model . The SMS group received up to eight text messages before delivery ( depending on gestational age ) , and six messages postpartum . Primary outcomes included maternal postpartum clinic attendance and virological infant HIV testing by 8 weeks postpartum . The primary analyses were intention-to-treat . Results : Of the 388 enrolled women , 381 ( 98.2 % ) had final outcome information . In the SMS group , 38 of 194 ( 19.6 % ) women attended a maternal postpartum clinic compared to 22 of 187 ( 11.8 % ) in the control group ( relative risk 1.66 , 95 % confidence interval 1.02–2.70 ) . HIV testing within 8 weeks was performed in 172 of 187 ( 92.0 % ) infants in the SMS group compared to 154 of 181 ( 85.1 % ) in the control group ( relative risk 1.08 , 95 % confidence interval 1.00–1.16 ) . Conclusions : Text messaging significantly improved maternal postpartum visit attendance , but overall return rates for these visits remained low . In contrast , high rates of early infant HIV testing were achieved in both arms , with significantly higher testing rates in the SMS compared to the control infants BACKGROUND Mobile text messaging is a potentially powerful tool for behaviour change because it is widely available , inexpensive , and instant . AIMS To evaluate whether mobile Text Messaging Service is a feasible mode of raising knowledge regarding maternal and child health ( MCH ) and to explore issues related to mobile text messages as a mode of health education . METHOD A community-based intervention study was conducted from January to June 2013 in six r and omly selected villages of Vellore district , Tamil Nadu . A multi-stage sampling technique was followed : 120 individuals from 120 households ( 30 clusters in six villages ) were contacted . Data was collected using a pretested question naire by house-to-house visits in three phases : 1 ) baseline assessment of aptitude towards text messages ; 2 ) intervention : sending MCH-related text messages ; and 3 ) end-line assessment to evaluate the increase in knowledge level . Qualitative data regarding mobile text messages as a mode of health education was explored . Quantitative data was analysed using SPSS version 17.0 and qualitative data by Anthropac software . RESULTS Of the individuals surveyed , 69.17 per cent and 52.5 per cent were " able to read " and " type and send " text messages , respectively . Seventy per cent of individuals were willing to receive health information via text messages , and 98.33 per cent believed text messages could effectively spread health messages . A significant increase in knowledge was observed following text messages . Male gender and subjects ' ability to read text messages were significantly associated . Factors related to mobile phone use include minimum economic burden , easy availability , portability , and ease of use . Factors related to mobile text messages as a mode of health message delivery include direct receipt of information , mass reach , the absence of regional language font in many h and sets , and illiterate individuals being unable to read messages . CONCLUSION In rural areas , mobile text messages have the potential to deliver health messages regarding MCH Long-term medication regimen adherence is challenging in all population s , but in the HIV-infected adolescent population the frequency of poverty , homelessness , substance abuse , and mental illness make highly active antiretroviral therapy ( HAART ) adherence even more challenging . In 2003 , we developed a pilot program for HIV-infected adolescents and young adults between the ages of 16 and 24 who were either going to begin a HAART regimen for the first time or begin a new HAART regimen . Participants received a free cell phone with a local service plan for approximately 6 months . Participants received phone call reminders for 12 weeks . Call frequency was tapered at 4-week intervals . Patients were assessed at 4-week intervals to determine the perceived intrusiveness or helpfulness of receiving calls , and missed medication doses . Eight consecutive patients were recruited for the study , and five were able to complete it through the 24 weeks . Most participants found the calls to be helpful and the level of intrusion into their daily lives acceptable . Using cell phone reminders to assist patients does not require an extensive amount of daily staff time . Tapering calls rapidly over 3 months , followed by discontinuation of calls provided inadequate support for subjects , especially those with significant psychosocial issues such as substance abuse . Use of cell phone reminders to assist adolescents adhere with HIV medications was practical and acceptable to pilot study participants . Viral suppression waned for all but two patients after termination of cell phone reminders and suggests that a 12-week intervention was not adequate for most subjects . Larger prospect i ve studies of cell phone observation of therapy will be needed to determine if this intervention can improve long-term adherence and health outcomes BACKGROUND Missed scheduled HIV appointments lead to increased mortality , resistance to antiretroviral therapy , and suboptimum virological response . We aim ed to assess whether reminders sent to carers by text message , mobile phone call , or concomitant text message and mobile phone call increase attendance at medical appointments for HIV care in a population of children infected with or exposed to HIV in Cameroon . We also aim ed to ascertain the most cost-effective method of mobile-phone-based reminder . METHODS MORE CARE was a multicentre , single-blind , factorial , r and omised controlled trial in urban , semi-urban , and rural setting s in Cameroon . Carers of children who were infected with or had been exposed to HIV were r and omly assigned electronically in blocks of four and allocated ( 1:1:1:1 ) sequentially to receive a text message and a call , a text message only , a call only , or no reminder ( control ) . Investigators were masked to group assignment . Text messages were sent and calls made 2 or 3 days before a scheduled follow-up appointment . The primary outcomes were efficacy ( the proportion of patients attending a previously scheduled appointment ) and efficiency ( attendance/ [ measures of staff working time × cost of the reminders ] ) , as a measure of cost-effectiveness . The primary analysis was by intention to treat . This study is registered with the Pan African Clinical Trials Register , number PACTR201304000528276 . FINDINGS The study took place between Jan 28 and May 24 , 2013 . We r and omly assigned 242 adult-child ( carer-patient ) pairs into four groups : text message plus call ( n=61 ) , call ( n=60 ) , text message ( n=60 ) , and control ( n=61 ) . 54 participants ( 89 % ) in the text message plus call group , 51 ( 85 % ) in the call group , 45 ( 75 % ) in the text message group , and 31 ( 51 % ) in the control group attended their scheduled appointment . Compared with control , the odds ratios for improvement in the primary efficacy outcome were 7·5 ( 95 % CI 2·9 - 19·0 ; p<0·0001 ) for text message plus call , 5·5 ( 2·3 - 13·1 ; p=0·0002 ) for call , and 2·9 ( 1·3 - 6·3 ; p=0·012 ) for text message . No significant differences were seen in comparisons of the three intervention groups with each other , and there was no synergism between text messages and calls . For the primary efficiency outcome , the mean difference for text message versus text message plus call was 1·5 ( 95 % CI 0·7 to 2·4 ; p=0·002 ) , for call versus text message plus call was 1·2 ( 0·7 to 1·6 ; p<0·0001 ) , and for call versus text message was 0·4 ( -1·3 to 0·6 ; p=0·47 ) . INTERPRETATION Mobile-phone-based reminders of scheduled HIV appointments for carers of paediatric patients in low-re source setting s can increase attendance . The most effective method of reminder was text message plus phone call , but text messaging alone was the most efficient ( ie , cost-effective ) method . FUNDING No external funding Objective To test the procedures proposed for a main trial of a safer sex intervention for young people delivered by mobile phone text message ( ‘ safetxt ’ ) . Design and setting Pilot r and omised controlled trial . Participants were recruited through sexual health services in the UK . An independent online r and omisation system allocated participants to receive the safetxt intervention or to receive the control text messages ( monthly messages about participation in the study ) . Texting software delivered the messages in accordance with a predetermined schedule . Participants Residents of Engl and aged 16–24 who had received either a positive chlamydia test result or reported unsafe sex in the last year ( defined as more than 1 partner and at least 1 occasion of sex without a condom ) . Intervention The safetxt intervention is design ed to reduce sexually transmitted infection in young people by supporting them in using condoms , telling a partner about an infection and testing before unprotected sex with a new partner . Safetxt was developed drawing on : behavioural science ; face-to-face interventions ; the factors known to influence safer sex behaviours and the views of young people . Outcomes The co primary outcomes of the pilot trial were the recruitment rate and completeness of follow-up . Results We recruited 200 participants within our target of 3 months and we achieved 81 % ( 162/200 ) follow-up response for the proposed primary outcome of the main trial , cumulative incidence of chlamydia at 12 months . Conclusions Recruitment , r and omisation , intervention delivery and follow-up were successful and a r and omised controlled trial of the safetxt intervention is feasible . Trial registration number IS RCT N02304709 ; Results Background Despite efforts to promote vaccination in low- and middle-income countries ( LMICs ) , over 20 million infants remain under-immunized and at risk for unnecessary morbidity and mortality . Mobile health technologies , such as Short Message Service ( SMS ) texts , have tremendous and untapped potential for disease management . Patient reminder systems are an important mechanism for improving childhood vaccination coverage and can be easily adapted to SMS platforms . However , current research lacks an underst and ing of the barriers and facilitators to mHealth program design , implementation , and scale in LMICs . Methods We analyzed survey data collected March-November 2016 at the enrollment visit from a r and omized controlled trial conducted at public health clinics in urban and rural Guatemala . Participants included eligible infants 6 weeks to 6 months of age receiving the first dose of the primary immunization series . At least one parent needed to own a mobile phone and be capable of deciphering SMS . Chi-square or Fisher 's exact and Student 's t-test were used to assess significance levels in demographic differences to describe factors that contribute to the feasibility of using an SMS-based vaccination reminder system . Results Of 1,088 families approached for enrollment , 871 were eligible and 720 ( 82.7 % ) participated with equal numbers of urban and rural children enrolled ; 54 parents did not own a mobile phone with SMS capability and three parents could not use SMS . There was no significant difference between urban and rural maternal mobile phone ownership ( 94.4 % vs. 93.3 % , P=0.53 ) , but more urban fathers owned mobile phones ( 72.8 % vs. 47.1 % , P<0.0001 ) and , overall , more mothers compared to fathers owned mobile phones ( 93.9 % vs. 61.1 % , P<0.0001 ) . Most families ( 90.4 % ) chose to have reminders sent to the mother . Urban participants reported more mobile phones present in the home ( P<0.0001 ) , but rural participants reported more telephone l and lines ( 34.7 % vs. 15.6 % , P<0.0001 ) . Most participants reported a daily average of ≤5 telephone calls made ( 87.4 % ) , ≤10 texts sent ( 91.0 % ) , and ≤10 texts received ( 89.9 % ) , with urban families reporting greater telephone usage ( P=0.006 , P<0.001 , and P<0.001 respectively ) . Parents preferred to make calls over sending texts ( 74.7 % vs. 25.3 % , P<0.0001 ) , with more urban families preferring text messaging ( 31.9 % vs. 18.6 % , P<0.0001 ) . Conclusions Our study results provide important insight into mobile phone access , usage , and preferences for voice and text communication across rural and urban population s of an LMIC that can be used to inform future mHealth interventions . Our findings suggest that offering a combination of more traditional communication methods with newer , modern technologies may be more effective at reminding families about vaccination visits , particularly for our rural population , and that targeting mothers for mobile phone interventions may provide the greatest benefits . Overall , our study suggests that using SMS reminders in LMICs can be a feasible tool for public health interventions Background : Resumption of sex before complete wound healing after male circumcision may increase risk of postoperative surgical complications , and HIV acquisition and transmission . We aim ed to determine the effect of text messaging to deter resumption of sex before 42 days postcircumcision . Methods : We conducted a r and omized trial where men older than18 years who owned mobile phones and had just undergone circumcision were r and omized to receive a series of text messages ( n = 600 ) or usual care ( n = 600 ) . The primary outcome was self-reported resumption of sex before 42 days . Results : Sex before 42 days was reported by 139 of 491 ( 28.3 % ) men in the intervention group and 124 of 493 ( 25.2 % ) men in the control group [ relative risk = 1.13 , 95 % confidence interval ( CI ) : 0.91 to 1.38 , P = 0.3 ] . Men were more likely to resume early if they were married or had a live-in sexual partner [ adjusted relative risk ( aRR ) 1.57 , 95 % CI : 1.18 to 2.08 , P < 0.01 ] ; in the month before circumcision had 1 ( aRR : 1.50 , 95 % CI : 1.07 to 2.12 , P = 0.02 ) or more than 1 ( aRR : 1.81 , 95 % CI : 1.24 to 2.66 , P < 0.01 ) sexual partner(s ) ; had primary school or lower education ( aRR : 1.62 , 95 % CI : 1.33 to 1.97 , P < 0.001 ) ; were employed ( aRR : 1.35 , 95 % CI : 1.05 to 1.72 , P = 0.02 ) ; or were 21–30 years old ( aRR : 1.58 , 95 % CI : 1.01 to 2.47 , P = 0.05 ) , 31–40 years old ( aRR : 1.91 , 95 % CI : 1.18 to 3.09 , P < 0.01 ) , or older than 40 years ( aRR : 1.76 , 95 % CI : 1.04 to 2.97 , P = 0.03 ) compared with younger than 21 years . Conclusions : Text messaging as used in this trial did not reduce early resumption of sex after circumcision . We identified key risk factors for early resumption that need to be considered in circumcision programs OBJECTIVE : To estimate whether text messages sent to ambulatory pregnant women could improve influenza vaccine uptake . METHODS : Obstetric patients at less than 28 weeks of gestation were enrolled in a r and omized controlled trial from an academic center 's outpatient clinic during two consecutive influenza seasons ( 2010–2011 and 2011–2012 ) . Potential participants were excluded if they had already received that season 's influenza vaccine . Participants were r and omized to receive 12 weekly text messages encouraging general pregnancy health ( General ) or general pregnancy health plus influenza vaccination ( Flu ) . Study participants completed preintervention and postintervention surveys about preventive health beliefs . Influenza vaccine receipt was assessed using prenatal record review . The study was powered to detect a 55 % increase in the vaccination rate in the intervention group . RESULTS : Two hundred sixteen women were enrolled , 204 of whom were available for intention-to-treat analysis ( n=100 General , n=104 Flu ) . Participants were primarily African American ( 66 % ) with low educational attainment ( 90 % equivalent to or less than high school education ) and predominantly with either public or no insurance ( 88 % ) . The overall influenza vaccination rate among participants was 32 % with no difference between participants in the General ( 31 % [ n=31 ] ) compared with Flu ( 33 % [ n=34 ] ) groups ( difference 1.7 % , 95 % confidence interval −11.1 to 14.5 % ) . CONCLUSION : Text messaging prompts were not effective at increasing influenza vaccination rates among a low-income , urban , ambulatory obstetric population . Ongoing efforts are needed to improve vaccine uptake among pregnant women unsure about or unwilling to receive influenza vaccination . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01248520 . LEVEL OF EVIDENCE : Background Medical abortion is legal in South Africa but access and acceptability are hampered by the current protocol requiring a follow-up visit to assess abortion completion . Objective To assess the feasibility and efficacy of information and follow-up provided via mobile phone after medical abortion in a r and omized controlled trial ( RCT ) . Methods Mobile phones were used in three ways in the study : ( 1 ) coaching women through medical abortion using short message service ( SMS ; text messages ) ; ( 2 ) a question naire to assess abortion completion via unstructured supplementary service data ( USSD , a protocol used by GSM mobile telephones that allows the user to interact with a server via text-based menus ) and the South African mobile instant message and social networking application Mxit ; and ( 3 ) family planning information via SMS , mobisite and Mxit . A needs and context assessment was done to learn about women ’s experiences undergoing medical abortion and their use of mobile phones . After development , the mobile interventions were piloted . Recruitment was done by field workers at the clinics . In the RCT , women were interviewed at baseline and exit . Computer logs were also analyzed . All study participants received st and ard of care at the clinics . Results In the RCT , 234 women were r and omized to the intervention group . Eight did not receive the intervention due to invalid numbers , mis- registration , system failure , or opt-out , leaving 226 participants receiving the full intervention . Of the 226 , 190 returned and were interviewed at their clinic follow-up visit . The SMSs were highly acceptable , with 97.9 % ( 186/190 ) saying that the SMSs helped them through the medical abortion . In terms of mobile phone privacy , 86.3 % ( 202/234 ) said that it was not likely or possible that someone would see SMSs on their phone , although at exit , 20 % ( 38/190 ) indicated that they had worried about phone privacy . Having been given training at baseline and subsequently asked via SMS to complete the self- assessment question naire , 90.3 % ( 204/226 ) attempted it , and of those , 86.3 % ( 176/204 ) reached an endpoint of the question naire . For the family planning information , a preference for SMS was indicated by study clients , although the publicly available Mxit/mobisite was heavily used ( 813,375 pages were viewed ) over the study duration . Conclusions SMS provided a good medium for timed , " push " information that guided and supported women through medical abortion . Women were able to perform a self- assessment question naire via mobile phones if provided training and prompted by SMS . Phone privacy needs to be protected in similar setting s. This study may contribute to the successful expansion of medical abortion provision aided by mobile phones . Trial Registration Pan African Clinical Trials Registry ( PACTR ) : PACTR201302000427144 ; http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201302000427144 ( Archived by WebCite at http://www.webcitation.org/6N0fnZfzm ) INTRODUCTION Failure to attend medical appointments among persons living with human immunodeficiency virus ( HIV ) has been associated with poor health outcomes . Text message appointment reminders are a novel tool to potentially improve appointment attendance , but the feasibility of this tool among persons living with HIV in the United States is unknown . SUBJECTS AND METHODS We conducted a r and omized , controlled trial of text message reminders in a large HIV clinic . Patients who declined enrollment were asked for reasons for declining . For all patients r and omized , demographic and clinical data were collected from medical records . RESULTS Of 94 patients screened for the study , 42 ( 45 % ) did not elect to participate ; the most common reason for declining participation was the lack of either a cell phone or text messaging service . Cost , comfort with text messaging , and privacy were other major barriers to study enrollment . Among the 25 subjects r and omized to receive text messages , 6 ( 24 % ) had their phones disconnected prior to the appointment reminder date . Ultimately , there were no differences in clinic attendance rates between the group that received text reminders versus the group that did not ( 72 % versus 81 % , p=0.42 ) in an intention-to-treat analysis . CONCLUSIONS Although text message reminders may be successful in certain groups of patients , barriers must be addressed before they are used as a universal approach to improve clinic attendance Background The risk of poor sexual health , including unplanned pregnancy and sexually transmitted infections ( STIs ) , is greatest amongst young people . Innovative and acceptable interventions to improve sexual health are required . Mobile phone text messaging ( short message service , SMS ) interventions have the potential to reach large numbers of people at relatively low cost , but greater underst and ing is needed on how these interventions should be developed and how they work . Objectives The aim of this paper is to explore young people ’s views of and experiences with a mobile phone text messaging intervention to promote safer sex behavior . Methods We undertook qualitative interviews with young people aged 16 to 24 years as part of a pilot trial of a sexual health intervention delivered by text message in the United Kingdom . Study participants received sexual health promotion text messages based on behavior-change techniques . The message content , tailored by gender and STI status , included support for correct STI treatment and promotion of safer sex behaviors . Young people were eligible if they had received a positive chlamydia test or had more than one partner and at least one episode of unprotected sex in the last year . Telephone interviews were conducted 2 to 3 weeks after initiation of the intervention . A semi-structured topic guide was followed to explore participant experiences and a thematic analysis was conducted . Results We conducted 16 telephone interviews with participants who had received the text intervention and an additional four interviews with those in the control group ( 13 women and 7 men ) . Intervention participants found text messages easy to underst and and appearing to come from a friendly and trustworthy source . They considered the frequency and timing of messages to be appropriate , and delivery via mobile phones convenient . Receipt of support by text message allowed recipients to assimilate information at their own pace , and prompted reflection on and sharing of messages with friends , family members , and partners , thus providing opportunities for education and discussion . For some recipients , the messages had increased their knowledge of how to correctly use condoms . Some described how the messages had increased their confidence and reduced stigma , enabling them to disclose infection to a partner and /or to do so sooner and more calmly . Discussing the messages with a partner reportedly enabled some women to negotiate condom use . Conclusion From the perspective of the recipients , the tone , frequency , and content of the text messaging-based sexual health intervention was acceptable and appropriate . Their accounts indicated that the intervention increased knowledge , confidence , and safer sex behaviors . A large-scale r and omized controlled trial ( RCT ) is needed to assess effectiveness Please cite this paper as : Lund S , Hemed M , Nielsen B , Said A , Said K , Makungu M , Rasch V. Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar : a cluster‐r and omised controlled trial . BJOG 2012;119:1256–1264 Objective To carry out a r and omised controlled trial on the effect of a new method of health promotion — email and mobile phone text messages ( short messaging service (SMS))—on young people 's sexual health . Methods 994 people aged 16–29 were recruited at a music festival to a non-blinded r and omised controlled trial . Participants were r and omised to either receive sexual health promotion messages ( n=507 ) or the control group ( n=487 ) . The 12-month intervention included SMS ( catchy sexually transmissible infections prevention slogans ) and emails . Participants completed question naires at the festival at baseline and online after 3 , 6 and 12 months . Outcomes were differences between the control and intervention groups in health-seeking behaviour , condom use with risky partners ( new or casual partners or two or more partners within 12 months ) and STI knowledge . Results 337 ( 34 % ) completed all three follow-up question naires and 387 ( 39 % ) completed the final question naire . At 12 months , STI knowledge was higher in the intervention group for both male ( OR=3.19 95 % CI 1.52 to 6.69 ) and female subjects ( OR=2.36 95 % CI 1.27 to 4.37 ) . Women ( but not men ) in the intervention group were more likely to have had an STI test ( OR=2.51 , 95 % CI 1.11 to 5.69 ) , or discuss sexual health with a clinician ( OR=2.92 , 95 % CI 1.66 to 5.15 ) than their control counterparts . There was no significant impact on condom use . Opinions of the messages were favourable . Conclusion This simple intervention improved STI knowledge in both sexes and STI testing in women , but had no impact on condom use . SMS and email are low cost , popular and convenient , and have considerable potential for health promotion . Clinical trial registration number Australian Clinical Trials Registry - ACTRN12605000760673 Background Clients diagnosed and treated for Chlamydia trachomatis are a recognised high-risk group for subsequent infection . An estimated 8 % of clients treated for chlamydia at Cairns Sexual Health Service return for re-testing within the recommended 3–4-month period . There is no recall or reminder system in place . This study assesses the effectiveness of using short messaging service ( SMS ) reminders with and without incentive payments to increase re-testing rates . Methods Eligible consenting clients were r and omly allocated to one of three groups . Group 1 ( controls ) received the st and ard advice from the clinician to return for re-testing in 3–4 months . Group 2 received the st and ard advice and an SMS reminder at 10–12 weeks post-treatment . Group 3 received the st and ard advice and the SMS reminder , which also offered an incentive payment on clinic attendance . Results 32 participants were recruited to groups 1 and 2 and 30 participants to group 3 . 62 SMS reminders were sent with 13 ( 21.0 % ) reported as undelivered . Re-testing rates were 6.3 % , 28.1 % and 26.7 % for groups 1 , 2 and 3 , respectively . Conclusion SMS reminders with or without an incentive payment increased re-testing rates in our clients who were diagnosed and treated for chlamydia . However , re-testing remained less than ideal , and the high rate of undelivered SMS reminders suggest that this intervention alone will not achieve desired re-testing rates and that a range of strategies will be required to increase re-testing in this population We compared the effectiveness of two media ( text messages and pamphlets ) in imparting health education to mothers of preschool children . Mothers and their children were r and omized into two groups . There were 72 mothers and their children in the pamphlet group and 71 in the text message group . The mothers were given health education by one of the two modes for four weeks . Knowledge , attitude and practice s of the mothers were assessed by a question naire pre- and post-intervention . Visible plaque scores of their children were also recorded pre- and post-intervention . There were significant improvements in knowledge ( P < 0.001 ) , attitude ( P < 0.001 ) and practice s ( P < 0.001 ) in both groups . There was also a significant reduction in visible plaque scores ( P < 0.001 ) in both groups . Text messaging was more effective than pamphlets in improving knowledge , attitude and practice s of mothers , but the comparative reduction in plaque score between groups was not significant . Text messaging appears to be an effective means of imparting oral health education STUDY OBJECTIVE Produce Girl Talk , a free smartphone application containing comprehensive sexual health information , and determine the application 's desirability and appeal among teenage girls . DESIGN , SETTING , PARTICIPANTS , AND INTERVENTIONS Thirty-nine girls ages 12 to 17 years from Rhode Isl and participated in a 2-phase prospect i ve study . In phase I , 22 girls assessed a sexual health question naire in focus groups . In phase II , 17 girls with iPhones used Girl Talk for 2 weeks and answered the revised sexual health question naire and interview questions before and after use . MAIN OUTCOME MEASURES Participants ' responses to the sexual health question naire , interviews , and time viewing the application were used to determine feasibility and desirability of Girl Talk . RESULTS Girl Talk was used on average for 48 minutes during participants ' free time on weekends for 10- to 15-minute intervals . Reported usefulness of Girl Talk as a sexual health application from baseline ( 6 participants ) to follow-up ( 16 participants ) increased significantly ( 35.3 % vs 94.1 % ; P < .001 ) . Knowledge improved most in topics related to anatomy and physiology ( 70.5 % to 74.7 % out of 7 questions ) , sexuality and relationships ( 76.5 % to 80.0 % out of 10 questions ) , and STI prevention ( 75.6 % to 79.0 % out of 7 questions ) . Most phase II participants ( 13 out of 17 , or 76.5 % ) were exposed to sexual health education before using Girl Talk , but 16 out of 17 participants ( 94.1 % ) stated that the application provided new and /or more detailed information than health classes . CONCLUSION Girl Talk can potentially connect teenage girls to more information about sexual health vs traditional methods , and participants recommended the application as a valuable re source to learn about comprehensive sexual health BACKGROUND Routine Immunization (RI)is known to beone of the most cost-effective public health strategies ever , and a cornerstone among all primary healthcare efforts but has been bedevilledin Low and Middle Income Countries ( LMICs ) in the last two decadesby poor coverage and lack of timeliness -both due , among other factors , to clients forgetting appointments . These setback RI effectiveness from ensuring herd immunity and preventing disease . Across the world , different cost-effective mobile telephone-based reminder systems are currently in use as strategies for improving coverage and compliance in various health interventions .Their application to RI is thereforehighly recommended . OBJECTIVE This study sought to provide evidence validating the need for development and deployment of automated client Reminder-Recall systems for the Nigerian National Routine Immunisation Program and to compare its projected cost withthe cost of a health personnel-based defaulter tracking system . METHODOLOGY A multi-centre , parallel-group , R and omized Controlled Trial was carried outusing multi-stage sampling . Nine hundred and five child-caregivers were followed-upat 8 health facilities in an urban/sub-urban area in South-South Nigeria . Text messagereminders were sent to the Intervention group only , with concurrent weekly data collection , including that for controls , at each of the enrolled health facilities . Recall messages were sent to defaulters and their responses ( presence at immunization session ) assessed the next RI session . Receipt of DPT3 vaccine on or before the 18th week was categorized early , while receiptafter was categorized delayed . RESULTS Clients in the Interventiongroup were1.5times earlier than Controls intheir receipt of DPT3 . Immunization coverage was also 8.7%better in the Interventiongroup . A first year estimate of cost of deploying this strategy was less than a quarter ofthe estimated cost of using home-visits which is the defaulter tracking method currently recommended by regulatory authorities . CONCLUSION Routine immunization performance was significantly better in the Interventiongroup who received SMS reminders compared to the controls who did not . Since this occurred at a cheaper rate than projected costs of home visits , in a habitual stock-out situation , this is ample evidence for health policy-makers in LMICs to leverage the ever exp and ing mobile telecom platforms for future sustainable improvements in routine immunisation performance and even other disease control efforts in Nigeria Many people newly diagnosed with HIV are lost to follow-up before timely initiation of antiretroviral therapy ( ART ) . A r and omised controlled trial ( RCT ) , WelTel Kenya1 , demonstrated the effectiveness of the WelTel text messaging intervention to improve clinical outcomes among patients initiating ART . In preparation for WelTel Retain , an RCT that will evaluate the effect of the intervention to retain patients in care immediately following HIV diagnosis , we conducted an informative qualitative study with people living with HIV ( n = 15 ) and healthcare providers ( HCP ) ( n = 5 ) in October 2012 . Study objectives included exploring the experiences of people living with HIV who have attempted to engage in HIV care , the use of cell phones in everyday life , and perceptions of communicating via text message with HCP . Participants were recruited through convenience sampling . Semi-structured , qualitative interviews were conducted and recorded , transcribed verbatim and analysed using NVivo software . Analysis was guided by the Theory of Reasoned Action and the Technology Acceptance Model . Results indicate that while individuals have many motivators for engaging in care after diagnosis , structural and individual barriers including poverty , depression and fear of stigma prevent them from doing so . All participants had access to a mobile phone , and most were comfortable communicating through text messages , or were willing to learn . Both people living with HIV and HCP felt that increased communication via the text messaging intervention has the potential to enable early identification of problems , leading to timely problem solving that may improve retention and engagement in care during the first year after diagnosis OBJECTIVE The main objective was to compare the satisfaction levels of antenatal care between healthy pregnant women who received short message service ( SMS ) via mobile phone for prenatal support , and those who did not . The second objective was to compare the confidence , anxiety levels and also pregnancy outcomes . DESIGN A r and omized controlled trial . MATERIAL AND METHOD 68 healthy pregnant women who attended the antenatal clinic and delivered at Siriraj Hospital , who met the inclusion criteria s between May 2007 and October 2007 , were enrolled and r and omly allocated into two r and om groups . The study group received two SMS messages per week from 28 weeks of gestation until giving birth . The other group was pregnant women who did not receive SMS . Both groups had the same antenatal and perinatal care . The satisfaction , confidence and anxiety scores were evaluated using a question naire at the postpartum ward . The pregnancy outcomes were also compared in these two groups . RESULTS The satisfaction levels of the women who received prenatal support in SMS messages , were significantly higher than those of who did not receive the messages both in the antenatal period ( 9.25 vs. 8.00 , p < 0.001 ) and during labor ( 9.09 vs. 7.90 , p = 0.007 ) . In the SMS using group , the confidence level was'higher ( 8.91 vs. 7.79 , p = 0.001 ) and the anxiety level was lower ( 2.78 vs. 4.93 , p = 0.002 ) than the control group n the antenatal period , however no diference in pregnancy outcomes were found . CONCLUSION The present study shows the higher satisfaction level of pregnant women who received SMS via mobile phone during their antenatal service when compared with the general antenatal care group . The study also show the higher confidence level and lower anxiety level in the antenatal period but no difference in pregnancy outcomes Voluntary medical male circumcision ( MMC ) reduces risk of HIV infection , but uptake remains suboptimal among certain age groups and locations in sub-Saharan Africa . We analysed qualitative data as part of the Linkages Study , a r and omized controlled trial to evaluate community-based HIV testing and follow-up as interventions promoting linkage to HIV treatment and prevention in Ug and a and South Africa . Fifty-two HIV-negative uncircumcised men participated in the qualitative study . They participated in semistructured individual interviews exploring ( a ) home HTC experience ; ( b ) responses to test results ; ( c ) efforts to access circumcision services ; ( d ) outcomes of efforts ; ( e ) experiences of follow-up support ; and ( f ) local HIV education and support . Interviews were audio-recorded , translated , transcribed , and summarized into “ linkage summaries . ” Summaries were analysed inductively to identify the following three thematic experiences shaping men 's circumcision choices : ( 1 ) intense relief upon receipt of an unanticipated seronegative diagnosis , ( 2 ) the role of peer support in overcoming fear , and ( 3 ) anticipation of missed economic productivity . Increased attention to the timing of dem and creation activities , to who delivers information about the HIV prevention benefits of MMC , and to the importance of missed income during recovery as a barrier to uptake promises to strengthen and sharpen future MMC dem and creation strategies BACKGROUND Social media technologies offer new approaches to HIV prevention and promotion of testing . We examined the efficacy of the Harnessing Online Peer Education ( HOPE ) social media intervention to increase HIV testing among men who have sex with men ( MSM ) in Peru . METHODS In this cluster r and omised controlled trial , Peruvian MSM from Greater Lima ( including Callao ) who had sex with a man in the past 12 months , were 18 years of age or older , were HIV negative or serostatus unknown , and had a Facebook account or were willing to create one ( N=556 ) were r and omly assigned ( 1:1 ) by concealed allocation to join intervention or control groups on Facebook for 12 weeks . For the intervention , Peruvian MSM were trained and assigned to be HIV prevention mentors ( peer-leaders ) to participants in Facebook groups . The interventions period lasted 12 weeks . Participants in control groups received an enhanced st and ard of care , including st and ard offline HIV prevention available in Peru and participation in Facebook groups ( without peer leaders ) that provided study up date s and HIV testing information . After accepting a request to join the groups , continued participation was voluntary . Participants also completed question naires on HIV risk behaviours and social media use at baseline and 12 week follow-up . The primary outcome was the number of participants who received a free HIV test at a local community clinic . The facebook groups were analysed as clusters to account for intracluster correlations . This trial is registered with Clinical Trials.gov , number NCT01701206 . FINDINGS Of 49 peer-leaders recruited , 34 completed training and were assigned at r and om to the intervention Facebook groups . Between March 19 , 2012 , and June 11 , 2012 , and Sept 26 , 2012 , and Dec 19 , 2012 , 556 participants were r and omly assigned to intervention groups ( N=278 ) or control groups ( N=278 ) ; we analyse data for 252 and 246 . 43 participants ( 17 % ) in the intervention group and 16 ( 7 % ) in the control groups got tested for HIV ( adjusted odds ratio 2·61 , 95 % CI 1·55–4·38 ) . No adverse events were reported . INTERPRETATION Development of peer-mentored social media communities seemed to be an efficacious method to increase HIV testing among high-risk population s in Peru . Results suggest that the HOPE social media intervention could improve HIV testing rates among MSM in Peru . FUNDING National Institute of Mental Health PURPOSE There is a dearth of HIV prevention/healthy sexuality programs developed for adolescent gay and bisexual males ( AGBM ) as young as 14 years old , in part because of the myriad ethical concerns . To address this gap , we present our ethics-related experiences implementing Guy2Guy , a text messaging-based HIV prevention/healthy sexuality program , in a r and omized controlled trial of 302 14- to 18-year-old sexual minority males . METHODS Potential risks and efforts to reduce these risks are discussed within the framework of the Belmont Report : Respect for persons , beneficence ( e.g. , risks and benefits ) , and justice ( e.g. , fair distribution of benefits and burdens ) . RESULTS To ensure " respect for persons , " online enrollment was coupled with telephone assent , which included assessing decisional capacity to assent . Beneficence was promoted by obtaining a waiver of parental permission and using a self-safety assessment to help youth evaluate their risk in taking part . Justice was supported through efforts to develop and test the program among those who would be most likely to use it if it were publicly available ( e.g. , youth who own a cell phone and are enrolled in an unlimited text messaging plan ) , along with the use of recruitment targets to ensure a racially , ethnically , and regionally diverse sample . CONCLUSIONS It is possible to safely implement a sensitive and HIV prevention/healthy sexuality program with sexual minority youth as young as 14 years old when a rigorous ethical protocol is in place Background Globally , non-attendance for immunization appointments remains a challenge to healthcare providers . A review of the 2011 immunization coverage for Kadoma City , Zimbabwe was 74 % for Oral Polio Vaccine ( OPV ) , Pneumococcal and Pentavalent antigens . The immunization coverage was less than 90 % , which is the target for Kadoma City . Adoption of short message services ( SMS ) reminders has been shown to enhance attendance in some medical setting s. The study was conducted to determine the effectiveness of SMS reminders on immunization programme for Kadoma City . Methods A r and omized controlled trial was conducted at Kadoma City clinics in Zimbabwe . Women who delivered and were residents of Kadoma City were recruited into the study . In the intervention group , SMS reminders were sent at 6 , 10 and 14 weeks in addition to routine health education . In the non-intervention no SMS reminders were used , however routine health education was offered . Data were collected using interviewer administered question naire . Data were analyzed using Epi Info 7 ™ , where frequencies , means , risk ratios and risk differences were generated . Results A total of 304 participants were recruited , 152 for the intervention group and 152 for the non-intervention group . The immunization coverage at 6 weeks was 97 % in the intervention group and 82 % in the non-intervention group ( p < 0.001 ) . At 14 weeks immunization coverage was 95 % for intervention and 75 % for non-intervention group ( p < 0.001 ) . Those who did not delay receiving immunization at 14 weeks was 82 % for the intervention and 8 % for non-intervention group . Median delay for intervention was 0 days ( Q1 = 0 ; Q3 = 0 ) and 10 days ( Q1 = 6 ; Q3 = 17 ) for non-intervention group . The risk difference ( RD ) for those who received SMS reminders than those in the non intervention group was 16.3 % ( 95 % CI : 12.5 - 28.0 ) at 14 weeks . Conclusion Immunization coverage in the intervention group was significantly higher than in non-intervention group . Overall increase in immunization coverage can be attributed to use of SMS.Trial registration IS RCT N70918594 . Registration Date : 28 August 2014 The purpose of this study was to examine the effect text messages ( TM ) immunization reminders have on immunization rates in the first 7 months of life . This r and omized-control trial enrolled 57 parent/infant dyads and had a 74 % completion rate ( 43 ) at the end of the study period . The study was approved by Committee on Human Subjects at the University of Hawaii Institutional Board Review . All participants completed a demographics form and a Barriers to Immunization Survey ( SHOTS survey ) at the start and end of the study . Parents received TM at 4 , 7 , 12 , 15 , 20 , & 23 weeks of child 's age . The intervention group received immunization reminders and the control group received healthy baby messages . In the overall mixed model , between enrollment and 7 months of age , the barriers to immunizations decreased for all parents significantly . There were no significant differences in immunization rates between groups at 7 months of age . Positive responses from regarding TM interventions show this is a promising intervention , but further research is required regarding how to address behavior change and motivation for health prevention behaviors with TM BACKGROUND Younger people bear the heaviest burden of sexually transmitted infections ( STIs ) . Partner notification , condom use and STI testing can reduce infection but many young people lack the knowledge , skills and confidence needed to carry out these behaviours . Text messages can provide effective behavioural support . The acceptability and feasibility of a r and omised controlled trial of safer sex support delivered by text message are not known . OBJECTIVES To assess the acceptability and feasibility of a r and omised controlled trial of a safer sex intervention delivered by text message for young people aged 16 - 24 years . DESIGN ( 1 ) Intervention development ; ( 2 ) follow-up procedure development ; ( 3 ) a pilot , parallel-arm r and omised controlled trial with allocation via remote automated r and omisation ( ratio of 1 : 1 ) ( participants were unmasked , whereas research ers analysing sample s and data were masked ) ; and ( 4 ) qualitative interviews . SETTING Participants were recruited from sexual health services in the UK . PARTICIPANTS Young people aged 16 - 24 years diagnosed with chlamydia or reporting unprotected sex with more than one partner in the last year . INTERVENTIONS A theory- and evidence -based safer sex intervention design ed , with young people 's input , to reduce the incidence of STIs by increasing the correct treatment of STIs , partner notification , condom use and STI testing before unprotected sex with a new partner . The intervention was delivered via automated mobile phone messaging over 12 months . The comparator was a monthly text message checking contact details . MAIN OUTCOME MEASURES ( 1 ) Development of the intervention based on theory , evidence and expert and user views ; ( 2 ) follow-up procedures ; ( 3 ) pilot trial primary outcomes : full recruitment within 3 months and follow-up rate for the proposed primary outcomes for the main trial ; and ( 4 ) participants ' views and experiences regarding the acceptability of the intervention . RESULTS In total , 200 participants were r and omised in the pilot trial , of whom 99 were allocated to the intervention and 101 were allocated to the control . We fully recruited early and achieved an 81 % follow-up rate for our proposed primary outcome of the cumulative incidence of chlamydia at 12 months . There was no differential follow-up between groups . In total , 97 % of messages sent were successfully delivered to participants ' mobile phones . Recipients reported that the tone , language , content and frequency of messages were appropriate . Messages reportedly increased knowledge of and confidence in how to use condoms and negotiate condom use and reduced stigma about STIs , enabling participants to tell a partner about a STI . CONCLUSIONS Our research shows that the intervention is acceptable and feasible to deliver . Our pilot trial demonstrated that a main trial is feasible . It remains unclear which behaviour change techniques and elements of the intervention or follow-up procedures are associated with effectiveness . A further limitation is that in the trial one person entering data and the participants were unmasked . A r and omised controlled trial to establish the effects of the intervention on STIs at 12 months is needed . TRIAL REGISTRATION Current Controlled Trials IS RCT N02304709 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 57 . See the NIHR Journals Library website for further project information Text4baby was launched in 2010 to promote healthy pregnancies and babies by the use of text messaging . The primary objective of this study was to assess factors related to the enrollment process and reception of text4baby . A prospect i ve cohort study was conducted in two Women , Infant and Children clinics in Atlanta ( April 2010–July 2011 ) . R and omly selected pregnant and postpartum women ( n = 468 ) were queried on cell phone use and instructed on text4baby enrollment . Self-enrollment issues were assessed at one-week follow-up ( n = 351 , 75.0 % ) , and message reception and reading patterns at two-month follow-up ( n = 209 , 44.7 % ) . Forty-two percent of the women had some college education and 82 % had household income < = $ 20,000 . About half attempted text4baby self-enrollment ( 162/351 ) , with enrollment success more likely among women with more education ( 80 % with some college vs. 62 % with less education ) , with household income above $ 10,000 ( 61 % < $ 10,000 vs. 83 % $ 10,001-$20,000 and 76 % > $ 20,000 ) , and among women living in smaller households ( 77 % 1–3 members vs. 58 % > 3 members ) ( all p < 0.001 ) . Among the 209 participants in the final follow-up contact , > 90 % reported uninterrupted reception and regular reading of messages , and 88 % planned to continue using text4baby . Results also suggested that respondents who were younger ( < 26 year ) , less educated and had lower health literacy skills were more likely to have interrupted messages . Despite substantial interest in the text4baby program in an underserved population , innovative ways to help women with significant disadvantages enroll and receive uninterrupted messages are needed OBJECTIVE To evaluate the effects of a mobile phone-based intervention on postnatal maternal health behavior and maternal and infant health in a middle-income country . METHODS A prospect i ve evaluation enrolled consecutive postpartum women at two public hospitals in Quito , Ecuador , between June and August 2012 . Inclusion criteria were live birth , no neonatal intensive care admission , and Spanish speaking . Intervention and control groups were assigned via r and om number generation . The intervention included a telephone-delivered educational session and phone/text access to a nurse for 30days after delivery . Maternal and infant health indicators were recorded at delivery and 3months after delivery via chart review and written/telephone-administered survey . RESULTS Overall , 102 women were assigned to the intervention group and 76 to the control group . At 3months , intervention participants were more likely to attend the infant 's postnatal check-up ( P=0.022 ) and to breastfeed exclusively ( P=0.005 ) , and less likely to feed formula ( P=0.016 ) . They used more effective forms of contraception ( more implants P=0.023 ; fewer condoms P=0.036 ) and reported fewer infant illnesses ( P=0.010 ) . There were no differences in maternal acute illness or check-up attendance . CONCLUSION Mobile phone-based postnatal patient education is a promising strategy for improving breastfeeding , contraceptive use , and infant health in low-re source setting s ; different strategies are needed to influence postpartum maternal health behavior INTRODUCTION Study aims were to assess the feasibility and acceptability of a tailored self-help smoking cessation intervention for pregnant smokers ( MiQuit ) . Secondary aims were to assess whether MiQuit affected cognitive determinants of quitting and to provide a range of potential effect sizes of the intervention effect on smoking abstinence . METHODS A r and omized controlled trial was undertaken in which pregnant smokers were allocated to either receive MiQuit , a tailored self-help leaflet followed by an 11-week program of tailored text messages , or to a control group , receiving a nontailored self-help leaflet . Participants were 207 pregnant smokers identified by community midwives across 7 NHS Trusts ( United Kingdom ) . At 3-month follow-up , intervention acceptability , cognitive determinants of quitting , and smoking outcomes ( self-reported and cotinine-vali date d 7-day point prevalence abstinence ) were assessed . RESULTS Feasibility : 94 % ( 95 % CI 89%-99 % ) of MiQuit participants reported receiving both intervention components . Acceptability : 9 % ( 95 % CI 4%-15 % ) of MiQuit participants opted to discontinue the text messages . Mechanism : compared with controls , MiQuit participants were more likely to set a quit date ( p = .049 ) and reported higher levels of self-efficacy ( p = .024 ) , harm beliefs ( p = .052 ) , and determination to quit ( p = .019 ) . Potential efficacy : self-reported abstinence-MiQuit 22.9 % , control 19.6 % ; odds ratio ( OR ) = 1.22 , 95 % CI 0.62 - 2.41 ; cotinine-vali date d abstinence-MiQuit 12.5 % , control 7.8 % ; OR = 1.68 , 95 % CI 0.66 - 4.31 . CONCLUSIONS Delivering tailored smoking cessation support to pregnant smokers via leaflet and text message is feasible and acceptable . The positive effects of MiQuit on cognitive determinants and the likelihood of setting a quit date are encouraging . A larger efficacy trial is warranted BACKGROUND Male circumcision decreases HIV acquisition by 60 % , and antiretroviral therapy ( ART ) almost eliminates HIV transmission from HIV-positive people who are virally suppressed ; however , coverage of these interventions has lagged behind targets . We aim ed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision . METHODS We did this multisite , open-label , r and omised controlled trial in six research -naive communities in rural South Africa and Ug and a. Eligible HIV-positive participants ( aged ≥16 years ) were r and omly assigned ( 1:1:1 ) in a factorial design to receive lay counsellor clinic linkage facilitation , lay counsellor follow-up home visits , or st and ard-of-care clinic referral , and then ( 1:1 ) either point-of-care CD4 cell count testing or referral for CD4 testing . HIV-negative uncircumcised men ( aged 16 - 49 years ) who could receive secure mobile phone text messages were r and omly assigned ( 1:1:1 ) to receive text message reminders , lay counsellor visits , or st and ard clinic referral . The study biostatistician generated the r and omisation schedule via a computer-generated r and om number program with varying block sizes ( multiples of six or three ) stratified by country . Primary outcomes for HIV-positive people were obtaining a CD4 cell count , linkage to an HIV clinic , ART initiation , and viral suppression at 9 months , and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months . We assessed social harms as a safety outcome throughout the study . We did the primary analyses by intention to treat . This trial is registered with Clinical Trials.gov , number NCT02038582 . FINDINGS Between June 6 , 2013 , and March 11 , 2015 , 15 332 participants were tested . 2339 ( 15 % ) participants tested HIV positive , of whom 1325 ( 57 % ) were r and omly assigned to receive lay counsellor clinic linkage facilitation ( n=437 ) , lay counsellor follow-up home visits ( n=449 ) , or st and ard clinic referral ( n=439 ) , and then point-of-care CD4 cell testing ( n=206 , n=220 , and n=213 , respectively ) or referral for CD4 testing ( n=231 , n=229 , and n=226 , respectively ) . 12 993 ( 85 % ) participants tested HIV negative , of whom 750 ( 6 % ) uncircumcised men were r and omly assigned to receive clinic referral ( n=230 ) , text message reminders ( n=288 ) , or lay counsellor follow-up visits ( n=232 ) . 1218 ( 93 % ) of 1303 HIV-positive participants were linked to care , but only 488 ( 37 % ) participants initiated ART . Overall , 635 ( 50 % ) of 1272 HIV-positive individuals achieved viral suppression at 9 months : 219 ( 52 % ) of 419 participants in the clinic facilitation group , 202 ( 47 % ) of 431 participants in the lay counsellor follow-up group , and 214 ( 51 % ) of 422 participants in the clinic referral group , with no significant differences between groups ( p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral ) . 523 ( 72 % ) of 734 HIV-negative men visited a circumcision facility , with no difference between groups . 62 ( 28 % ) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 ( 48 % ) of 284 men in the text message reminder group ( relative risk 1·72 , 95 % CI 1·36 - 2·17 ; p<0·0001 ) and 106 ( 47 % ) of 226 men in the lay counsellor follow-up group ( 1·67 , 1·29 - 2·14 ; p=0·0001 ) . No cases of study -related social harm were reported , including probing about partnership separation , unintended disclosure , gender-based violence , and stigma . INTERPRETATION All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics , roughly a third of whom initiated ART , and of those more than 80 % were virally suppressed at 9 months . Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received st and ard-of-care clinic referral . Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression . FUNDING National Institute of Allergy and Infectious Diseases , National Institutes of Health BACKGROUND Using a multidimensional approach , we assessed young women 's knowledge of oral contraceptives ( OC ) and its influence on OC continuation rates . METHODS We used data from 659 women aged 13 - 25 years participating in a r and omized controlled trial of an educational text message OC continuation intervention . Women received 6 months of daily text messages or routine care . At baseline and 6 months , we administered a comprehensive 41-item question naire measuring knowledge of OC 's mechanism , effectiveness , use , side effects , risks , and benefits . We ascertained OC continuation status and reasons for discontinuation at 6 months . We analyzed relationships between OC knowledge and continuation with multivariable logistic regression . RESULTS Young women scored , on average , 22.8 out of 41 points on the OC knowledge assessment at baseline and 24.7 points at 6 months . The 6-month OC continuation rate was 59 % . OC continuers had > 2-points-higher OC knowledge scores at 6 months than discontinuers ( p<0.001 ) . Those who reported discontinuing their OCs for side effects and forgetfulness scored > 2 points lower than women who discontinued for other reasons ( p-values<0.001 ) . In multivariable regression models , each correct response on the baseline and 6-month knowledge assessment s was associated with a 4 % and 6 % increased odds of OC continuation , respectively . Six-month OC knowledge scores were negatively associated with OC discontinuation due to side effects ( odds ratio [ OR ] 0.94 ) and forgetfulness ( OR 0.88 ) . CONCLUSIONS OC knowledge , which was low among young women in our study , was associated with OC continuation and common reasons for discontinuation . Continued efforts to characterize relationships between OC knowledge and behavior and to test the effectiveness of different components of interventions aim ed at increasing knowledge , addressing side effects , and improving use of OCs are warranted Many young children identified with developmental concerns in pediatric setting s do not receive early intervention ( EI ) . We assessed the impact of a video decision aid and text message reminder on knowledge and attitudes regarding developmental delay and EI as well as referral completion . We conducted a pilot r and omized controlled trial in an urban setting and enrolled 64 parent-child dyads referred to EI . Compared with controls , participants who received the intervention demonstrated increased knowledge regarding developmental delay and EI as well as more favorable attitudes in certain topics . Although we did not find a significant difference between arms in EI intake and evaluation , we found a pattern suggestive of increased intake and evaluation among participants with low health literacy in the intervention arm . Additional study is needed to identify strategies that improve the EI referral process for families and to underst and the potential targeted role for decision aids and text messages OBJECTIVE Traditionally breastfeeding education programs target mothers solely . The objective of this study was to design and pilot test an interactive eHealth breastfeeding co-parenting re source developed to target both mothers and fathers . eHealth re sources provide an accessible and engaging format on which to educate parents and assist them in meeting their breastfeeding goals . Best practice s to design such re sources are not currently known . DESIGN A three phase pilot study was conducted . The three phases included conducting a needs assessment , creating the re source and pilot testing the re source with mother , father and health care professionals to determine their perspectives regarding the usability and design of the prototype re source . The interactive prototype re source was design ed to provide information to parents on breastfeeding and co-parenting , which included suggestions on how fathers can be involved and support breastfeeding and how the couples can work as a team to meet their breastfeeding goals . Setting : Recruitment took place in a health region in Southern Ontario , Canada between June 2014 and March 2015 . Online question naires were completed by participants in all phases of the study . PARTICIPANTS Participants ( n=149 ) were pregnant or new mothers and their partners in the health region who read and speak English and had access to the internet and health care professionals who work with breastfeeding families in Ontario , Canada . INTERVENTION A prototype eHealth breastfeeding co-parenting re source was developed based on maternal and paternal feedback from Phase I and utilized an interactive interface which included games and multimodal information delivery . The prototype eHealth re source was provided to the parents in Phase II and health care professionals in Phase III . The final re source was created based on feedback from these participants . MEASUREMENTS AND FINDINGS The re source was pilot tested with new and expectant parents using pre- and post-test question naires which included measures for breastfeeding self-efficacy ( Breastfeeding Self-Efficacy Short Form ) , infant feeding attitude ( Iowa Infant Feeding Attitude Scale ) , breastfeeding knowledge ( Breastfeeding Knowledge Question naire ) and co-parenting relationship ( Co-parenting Relationship Scale ) . Maternal and paternal breastfeeding self-efficacy and knowledge and infant feeding attitude scores all increased from pre-test to post-test . However , there was no difference in the co-parenting relationship scores from pretest to post-test . KEY CONCLUSIONS This study has used feedback from parents and health professionals to develop a prototype re source which appears to be effective in increasing parents ' breastfeeding knowledge , attitude and self-efficacy . The prototype re source was rated positively by parents and health care providers . IMPLICATION S FOR PRACTICE An eHealth breastfeeding co-parenting re source design ed with input from the target population is an effective way of providing information to mothers and fathers . Further research with a r and omized controlled design and more diverse population s is needed to determine effectiveness of the re source on breastfeeding duration and exclusivity OBJECTIVES Home use of misoprostol for medical abortion is more convenient for many women than in-clinic use but requires management of abortion symptoms at home without provider backup . This study evaluated whether automated text messages to women undergoing medical abortion can reduce anxiety and emotional discomfort , and whether the messages can better prepare women for symptoms they experience . STUDY DESIGN A multisite r and omized controlled trial was conducted in which women undergoing early medical abortion were allocated to receive st and ard of care ( SOC ) only ( n=235 ) or SOC+a messaging intervention ( n=234 ) . Consenting women were interviewed at the clinic after taking mifepristone and again at their follow-up clinic visit 2 - 3 weeks later ; the intervention group received text messages over the duration of this period . Emotional outcomes were evaluated using the Hospital Anxiety and Depression Scale , Adler 's 12-item emotional scale and the Impact of Event Scale-Revised . Preparedness for the abortion symptoms and overall satisfaction with the procedure were assessed using 4-point Likert-type scales . RESULTS Between baseline and follow-up , anxiety decreased more ( p=0.013 ) , and less emotional stress was experienced ( adjusted for baseline anxiety , p=0.015 ) , in the intervention compared to the SOC group . Participants in the intervention group were also more likely to report that they felt very well prepared for the bleeding ( p<0.001 ) , pain ( p=0.042 ) and side effects ( p=0.027 ) they experienced . Acceptability and other negative emotions relating to the abortion did not differ between study groups . Ninety-nine percent of the intervention group stated that they would recommend the messages to a friend having the same procedure . CONCLUSIONS Text messages to women following mifepristone administration for early medical abortion may assist them in managing symptoms and appear highly acceptable to recipients . IMPLICATION STATEMENT This r and omized controlled trial provides evidence for the effectiveness of text messages following mifepristone administration in strengthening medical abortion care . The messages were associated with significant reductions in women 's anxiety and stress during the abortion process ; they improved preparedness for the abortion symptoms experienced and appeared highly acceptable |
524 | 28,578,899 | To reduce BP in adults with HTN , there is strong evidence to recommend provision of medical nutrition therapy by an RDN , adoption of the Dietary Approaches to Stop Hypertension dietary pattern , calcium supplementation , physical activity as a component of a healthy lifestyle , reduction in dietary sodium intake , and reduction of alcohol consumption in heavy drinkers .
Finally , recommendations related to lowering BP were formulated on vitamin D , magnesium , and the putative role of alcohol consumption in moderate drinkers ( weak evidence ) . | Hypertension ( HTN ) or high blood pressure ( BP ) is among the most prevalent forms of cardiovascular disease and occurs in approximately one of every three adults in the United States .
The purpose of this Evidence Analysis Library ( EAL ) guideline is to provide an evidence -based summary of nutrition therapy for the management of HTN in adults aged 18 years or older .
Implementation of this guideline aims to promote evidence -based practice decisions by registered dietitian nutritionists ( RDNs ) , and other collaborating health professionals to decrease or manage HTN in adults while enhancing patient quality of life and taking into account individual preferences . | BACKGROUND Although the Dietary Approaches to Stop Hypertension ( DASH ) diet is an accepted nonpharmacologic treatment for hypertension , little is known about what patient characteristics affect dietary adherence and what level of adherence is needed to reduce blood pressure ( BP ) . OBJECTIVE Our aim was to determine what factors predict dietary adherence and the extent to which dietary adherence is necessary to produce clinical ly meaningful BP reductions . DESIGN Ancillary study of the ENCORE ( Exercise and Nutrition Interventions for Cardiovascular Health ) trial -- a 16-week r and omized clinical trial of diet and exercise . PARTICIPANTS / SETTING Participants included 144 sedentary , overweight , or obese adults ( body mass index 25 to 39.9 ) with high BP ( systolic 130 to 159 mm Hg and /or diastolic 85 to 99 mm Hg ) . INTERVENTION Patients were r and omized to one of three groups : DASH diet alone , DASH diet plus weight management , and Usual Diet Controls . MAIN OUTCOMES MEASURES Our primary outcomes were a composite index of adherence to the DASH diet and clinic BP . STATISTICAL ANALYSES PERFORMED General linear models were used to compare treatment groups on post-treatment adherence to the DASH diet . Linear regression was used to examine potential predictors of post-treatment DASH adherence . Analysis of covariance was used to examine the relation of adherence to the DASH diet and BP . RESULTS Participants in the DASH diet plus weight management ( 16.1 systolic BP [ SBP ] ; 95 % CI 13.0 to 19.2 mm Hg and 9.9 diastolic BP [ DBP ] ; 95 % CI 8.1 to 11.6 mm Hg ) and DASH diet alone ( 11.2 SBP ; 95 % CI 8.1 to 14.3 mm Hg and 7.5 DBP ; 95 % CI 5.8 to 9.3 mm Hg ) groups showed significant reductions in BP in comparison with Usual Diet Controls participants ( 3.4 SBP ; 95 % CI 0.4 to 6.4 mm Hg and DBP 3.8 ; 95 % CI 2.2 to 5.5 mm Hg ) . Greater post-treatment consumption of DASH foods was noted in both the DASH diet alone ( mean = 6.20 ; 95 % CI 5.83 to 6.57 ) and DASH diet plus weight management groups ( mean = 6.23 ; 95 % CI 5.88 to 6.59 ) compared with Usual Diet Controls ( mean = 3.66 ; 95 % CI 3.30 to 4.01 ; P<0.0001 ) , and greater adherence to the DASH diet was associated with larger reductions in clinic SBP and DBP ( P ≤ 0.01 ) . Only ethnicity predicted dietary adherence , with African Americans less adherent to the DASH diet compared with whites ( 4.68 ; 95 % CI 4.34 to 5.03 vs 5.83 ; 95 % CI 5.50 to 6.11 ; P<0.001 ) . CONCLUSIONS Greater adherence to the DASH diet was associated with larger BP reductions independent of weight loss . African Americans were less likely to be adherent to the DASH dietary eating plan compared with whites , suggesting that culturally sensitive dietary strategies might be needed to improve adherence to the DASH diet R and omized trials have shown that increasing potassium intake lowers blood pressure . However , most previous trials used potassium chloride , whereas potassium in fruits and vegetables is not a chloride salt . It is unclear whether a nonchloride salt of potassium has a greater or lesser effect on blood pressure compared with potassium chloride . We performed a r and omized crossover trial comparing potassium chloride with potassium citrate ( 96 mmol/d , each for 1 week ) in 14 hypertensive individuals . At baseline , blood pressure was 151±16/93±7 mm Hg with a 24-hour urinary potassium of 81±24 mmol . During the r and omized crossover part of the study , blood pressure was 140±12/88±7 mm Hg with potassium chloride ( 24-hour urinary potassium : 164±36 mmol ) and 138±12/88±6 mm Hg with potassium citrate ( 24-hour urinary potassium : 160±33 mmol ) . These blood pressures were significantly lower compared with that at baseline ; however , there was no significant difference in blood pressure between potassium chloride and potassium citrate , mean difference ( 95 % confidence interval ) : 1.6 ( −2.3 to 5.6 ) mm Hg for systolic and 0.6 ( −2.4 to 3.7 ) mm Hg for diastolic . Our results , in conjunction with the evidence from many previous trials that potassium chloride has a significant blood pressure-lowering effect , suggest that potassium citrate has a similar effect on blood pressure as potassium chloride . These results support other evidence for an increase in potassium intake and indicate that potassium does not need to be given in the form of chloride to lower blood pressure . Increasing the consumption of foods high in potassium is likely to have the same effect on blood pressure as potassium chloride BACKGROUND Weight loss reduces blood pressure , and the Dietary Approaches to Stop Hypertension ( DASH ) diet has also been shown to lower blood pressure . OBJECTIVE Our goal was to assess the effect on blood pressure of 2 weight-reduction diets : a low-fat diet ( LF diet ) and a moderate-sodium , high-potassium , high-calcium , low-fat DASH diet ( WELL diet ) . DESIGN After baseline measurements , 63 men were r and omly assigned to either the WELL or the LF diet for 12 wk , and both diet groups undertook 0.5 h of moderate physical activity on most days of the week . RESULTS Fifty-four men completed the study . Their mean ( + /-SD ) age was 47.9 + /- 9.3 y ( WELL diet , n = 27 ; LF diet , n = 27 ) , and their mean baseline home systolic and diastolic blood pressures were 129.4 + /- 11.3 and 80.6 + /- 8.6 mm Hg , respectively . Body weight decreased by 4.9 + /- 0.6 kg ( + /-SEM ) in the WELL group and by 4.6 + /- 0.6 kg in the LF group ( P < 0.001 for both ) . There was a greater decrease in blood pressure in the WELL group than in the LF group [ between-group difference ( week 12 -baseline ) in both SBP ( 5.5 + /- 1.9 mm Hg ; P = 0.006 ) and DBP ( 4.4 + /- 1.2 mm Hg ; P = 0.001 ) ] . CONCLUSIONS For a comparable 5-kg weight loss , a diet high in low-fat dairy products , vegetables , and fruit ( the WELL diet ) result ed in a greater decrease in blood pressure than did the LF diet . This dietary approach to achieving weight reduction may confer an additional benefit in reducing blood pressure in those who are overweight K-rich fruit and vegetables may lower blood pressure ( BP ) and improve vascular function . A r and omised controlled trial ( IS RCT N50011192 ) with a cross-over design was conducted in free-living participants with early stages of hypertension ( diastolic BP>80 and < 100 mmHg , not receiving BP-lowering medication ) to test this hypothesis . Following a 3-week run-in period on a control diet , each subject completed four dietary 6-week dietary interventions ( control+placebo capsules , an additional 20 or 40 mmol K(+)/d from fruit and vegetables or 40 mmol potassium citrate capsules/d ) using a Latin square design with a washout period ≥ 5 weeks between the treatment periods . Out of fifty-seven subjects who were r and omised , twenty-three male and twenty-five female participants completed the study ; compliance to the intervention was corroborated by food intake records and increased urinary K(+ ) excretion ; plasma lipids , vitamin C , folate and homocysteine concentrations , urinary Na excretion , and body weight remained were unchanged . On the control diet , mean ambulatory 24 h systolic/diastolic BP were 132·3 ( sd 12·0)/81·9 ( ( SD ) 7·9 ) mmHg , and changes ( Bonferroni 's adjusted 95 % CI ) compared with the control on the diets providing 20 and 40 mmol K(+)/d as fruit and vegetables were 0·8 ( - 3·5 , 5·3)/0·8 ( - 1·9 , 3·5 ) and 1·7 ( - 3·0 , 5·3)/1·5 ( - 1·5 , 4·4 ) , respectively , and were 1·8 ( - 2·1 , 5·8)/1·4 ( - 1·6 , 4·4 ) mmHg on the 40 mmol potassium citrate supplement , and were not statistically significant . Arterial stiffness , endothelial function , and urinary and plasma isoprostane and C-reactive protein ( CRP ) concentrations did not differ significantly between the diets . The present study provides no evidence to support dietary advice to increase K intake above usual UK intakes in the subjects with early stages of hypertension Background The incidence of Hypertension as a major cardiovascular threat is increasing . The best known diet for hypertensives is ' no added salt diet'.In this study we evaluated the effect of ' no added salt diet ' on a hypertensive population with high dietary sodium intake by measuring 24 hour urinary sodium excretion . Methods In this single center r and omized study 80 patients ( 60 cases and 20 controls ) not on any drug therapy for hypertension with mild to moderate hypertension were enrolled . 24 hour holter monitoring of BP and 24 hour urinary sodium excretion were measured before and after 6 weeks of ' no added salt diet ' . Results There was no statistically significant difference between age , weight , sex , Hyperlipidemia , family history of hypertension , mean systolic and diastolic BP during the day and at night and mean urinary sodium excretion in 24 hour urine of case and control groups . Seventy eight percent of all patients had moderate to high salt intake . After 6 week of ' no added salt diet ' systolic and diastolic BP significantly decreased during the day ( mean decrease : 12.1/6.8 mmhg ) and at night ( mean decrease : 11.1/5.9 mmhg ) which is statistically significant in comparison to control group ( P 0.001 and 0.01).Urinary sodium excretion of 24 hour urine decreased by 37.1 meq/d ± 39,67 mg/dl in case group which is statistically significant in comparison to control group ( p : 0.001).Only 36 % of the patients , after no added salt diet , reached the pretreatment goal of 24 hour urinary sodium excretion of below 100 meq/dl ( P:0.001 ) . Conclusion Despite modest effect on dietary sodium restriction , no added salt diet significantly decreased systolic and diastolic BP and so it should be advised to every hypertensive patient . Trial Registration Clinical trial.govnumber BACKGROUND Low 25-hydroxy-vitamin D ( 25(OH)D ) levels are inversely related to blood pressure ( BP ) and have been associated with incident hypertension . In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency . We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension . METHODS We investigated the effect of 75 µg ( 3,000 IU ) cholecalciferol per day in a r and omized , placebo-controlled , double-blind study in 130 hypertensive patients residing in Denmark ( 56º N ) . Ambulatory BP ( 24-h BP ) and arterial stiffness were measured before and after 20 weeks of treatment , that took place between October and March . RESULTS A total of 112 patients ( mean age 61 ± 10 ) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study . Compared with placebo , a nonsignificant 3/1 mm Hg ( P = 0.26/0.18 ) reduction was found in 24-h BP . In patients with vitamin D insufficiency ( < 32 ng/ml ) at baseline ( n = 92 ) , 24-h BP decreased by 4/3 mm Hg ( P = 0.05/0.01 ) . Central BP ( CBP ) estimated by applanation tonometry and calibrated with a st and ardized office BP was reduced by 7/2 mm Hg ( P = 0.007/0.15 ) vs. placebo . No differences in carotid-femoral pulse wave velocity ( PWV ) or central augmentation index ( AIx ) were found between treatment arms . CONCLUSIONS Cholecalciferol supplementation , by a dose that effectively increased vitamin D levels , did not reduce 24-h BP , although central systolic BP decreased significantly . In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels < 32 ng/ml , significant decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation This study examined the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on insulin sensitivity and lipids . In a r and omized control trial , 144 overweight ( body mass index : 25 to 40 ) men ( n=47 ) and women ( n=97 ) with high blood pressure ( 130 to 159/85 to 99 mm Hg ) were r and omly assigned to one of the following groups : ( 1 ) DASH diet alone ; ( 2 ) DASH diet with aerobic exercise and caloric restriction ; or ( 3 ) usual diet controls ( UC ) . Body composition , fitness , insulin sensitivity , and fasting lipids were measured before and after 4 months of treatment . Insulin sensitivity was estimated on the basis of glucose and insulin levels in the fasting state and after an oral glucose load . Participants in the DASH diet with aerobic exercise and caloric restriction condition lost weight ( −8.7 kg [ 95 % CI : −2.0 to −9.7 kg ] ) and exhibited a significant increase in aerobic capacity , whereas the DASH diet alone and UC participants maintained their weight ( −0.3 kg [ 95 % CI : −1.2 to 0.5 kg ] and + 0.9 kg [ 95 % CI : 0.0 to 1.7 kg ] , respectively ) and had no improvement in exercise capacity . DASH diet with aerobic exercise and caloric restriction demonstrated lower glucose levels after the oral glucose load , improved insulin sensitivity , and lower total cholesterol and triglycerides compared with both DASH diet alone and UC , as well as lower fasting glucose and low-density lipoprotein cholesterol compared with UC . DASH diet alone participants generally did not differ from UC in these measures . Combining the DASH diet with exercise and weight loss result ed in significant improvements in insulin sensitivity and lipids . Despite clinical ly significant reductions in blood pressure , the DASH diet alone , without caloric restriction or exercise , result ed in minimal improvements in insulin sensitivity or lipids Background Hypertension can be prevented by adopting healthy dietary patterns . Our aim was to assess the 4-year effect on blood pressure ( BP ) control of a r and omized feeding trial promoting the traditional Mediterranean dietary pattern . Methods The PREDIMED primary prevention trial is a r and omized , single-blinded , controlled trial conducted in Spanish primary healthcare centers . We recruited 7,447 men ( aged 55 to 80 years ) and women ( aged 60 to 80 years ) who had high risk for cardiovascular disease . Participants were assigned to a control group or to one of two Mediterranean diets . The control group received education on following a low-fat diet , while the groups on Mediterranean diets received nutritional education and also free foods ; either extra virgin olive oil , or nuts . Trained personnel measured participants ’ BP at baseline and once yearly during a 4-year follow-up . We used generalized estimating equations to assess the differences between groups during the follow-up . Results The percentage of participants with controlled BP increased in all three intervention groups ( P-value for within-group changes : P<0.001 ) . Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group ( −1.53 mmHg ( 95 % confidence interval ( CI ) −2.01 to −1.04 ) for the Mediterranean diet supplemented with extra virgin olive oil , and −0.65 mmHg ( 95 % CI -1.15 to −0.15 ) mmHg for the Mediterranean diet supplemented with nuts ) . No between-group differences in changes of systolic BP were seen . Conclusions Both the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP . However , we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group . Trial registration Current Controlled Trials IS RCT BACKGROUND Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults , surprisingly little data exist to confirm the efficacy of these interventions in older persons . METHODS We conducted a r and omized , controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg . The experimental arm was a nonpharmacologic intervention combining weight reduction , sodium restriction , and increased physical activity . The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase , followed by four monthly group sessions during the maintenance phase . The control group received no treatment during the study . Blood pressure was assessed by certified technicians ( blinded to group assignment ) using r and om zero sphygmomanometers . RESULTS Of 56 participants r and omized , 47 completed the entire 6-month trial ( 21 in the intervention group and 26 in the control group ) . Attendance at the intervention sessions was excellent . The intervention group lost more weight ( -2.1 kg ) over 6 months than the control group ( + 0.3 kg ) . Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups , with greater trend in the intervention group , were not statistically significant . The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group ( mean differences between groups at 6 months , 4.2/4.9 mm Hg , respectively ) . CONCLUSIONS Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals The mechanism underlying blood pressure ( BP ) reduction in the high fruits and vegetables arm of the Dietary Approaches to Stop Hypertension ( DASH ) study is unknown but may include potassium , magnesium and fibre . This study was design ed to separate minerals and fibre from other components of DASH on BP in abdominally obese individuals with metabolic syndrome with pre-hypertension to stage 1 hypertension ( obese hypertensives ) . A total of 15 obese hypertensives and 15 lean normotensives were studied on a st and ardized usual diet , r and omized to DASH or usual diet supplemented with potassium , magnesium and fibre to match DASH , then crossed over to the complementary diet . All diets were 3 weeks long , isocaloric and matched for sodium and calcium . In obese hypertensives , BP was lower after 3 weeks on DASH than usual diet ( −7.6±1.4/−5.3±1.4 mm Hg , P<0.001/0.02 ) and usual diet supplemented ( −6.2±1.4/−3.7±1.4 P<0.005/0.06 ) , whereas BP was not significantly different on usual and supplemented diets . BP values were not different among the three diets in lean normotensives . Small artery elasticity was lower in obese hypertensives than in lean normotensives on the usual and supplemented diets ( P<0.02 ) . This index of endothelial function improved in obese hypertensives ( P<0.02 ) but not lean normotensives on DASH , and was no longer different from values in lean normotensives ( P>0.50 ) . DASH is more effective than potassium , magnesium and fibre supplements for lowering BP in obese hypertensives , which suggest that high fruits and vegetables DASH lowers BP and improves endothelial function in this group by nutritional factors in addition to potassium , magnesium and fibre Aims : To evaluate the effects of a lifestyle intervention programme in primary healthcare , targeted to patients with moderate to high risk of cardiovascular disease in terms of cardiovascular risk factors , physical activity , and quality of life . Method : R and omized controlled trial with one-year follow-up , carried out in a primary healthcare centre in Northern Sweden . A total of 151 middle-aged men and women , with hypertension , dyslipidemia , type 2 diabetes , or obesity were enrolled . The subjects were r and omized to either the intervention ( n=75 ) or the control group ( n=76 ) . A total of 123 subjects completed the one-year follow-up . Interventions : Exercise : supervised endurance and circuit training in groups three times a week for three months . Diet : five group sessions of diet counselling with a dietitian . Follow- up meetings with a physiotherapist were conducted monthly thereafter . Primary outcomes were changes in anthropometry , maximal oxygen uptake , health-related quality of life , and self-reported physical activity . The secondary outcomes were changes in blood pressure and metabolic variables . Results : After one year the intervention group significantly increased maximal oxygen uptake , physical activity , and quality of life and significantly decreased body weight , waist and hip circumference , body mass index , waist — hip ratio , systolic and diastolic blood pressure , triglycerides , and glycosylated haemoglobin . There were significant differences between groups , mean changes ( and their 95 % confidence intervals , CI ) in waist circumference -1.9 cm ( -2.80 to -0.90 ; p<0.001 ) , in waist — hip ratio -0.01 ( -.02 to -0.004 ; p<0.01 ) and in diastolic blood pressure -2.3 mmHg ( -4.04 to -0.51 ; p<0.05 ) . Conclusion : A prevention programme in primary healthcare with a focus on physical activity and diet counselling followed by structured follow-up meetings can favourably influence several risk factors for cardiovascular diseases and quality of life in high-risk subjects for at least one year BACKGROUND Calcium ( Ca2 + ) supplementation has been shown paradoxically to reduce intracellular Ca2 + and induce vascular relaxation . The aim of the study was to assess 24-h blood pressure ( BP ) change after Ca2 + supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange ( NHE-1 ) in subjects with hypertension and type 2 diabetes . METHODS This parallel , r and omized controlled , single-blinded trial , consisted of 31 patients with type 2 diabetes , and hypertension who were allocated to receive 1,500 mg of Ca2 + per day ( n = 15 ) or no treatment ( n = 16 ) for 8 weeks . RESULTS In the Ca2 + group a decrease of 1.7 + /- 2.7 mm Hg ( mean + /- SE ) P = 0.52 for mean 24-h systolic BP ( SBP ) and 2.1 + /- 1.5 mm Hg , P = 0.19 for mean 24-h diastolic BP ( DBP ) was recorded . Whereas in the control group an increase of 1.4 + /- 2.7 mm Hg , P = 0.59 for mean 24-h SBP and 1.2 + /- 2.8 mm Hg , P = 0.83 for mean 24-h DBP was observed . Intraplatelet Ca2 + decreased whereas intraplatelet magnesium ( Mg2 + ) and erythrocyte K+ increased in the intervention group . Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2 + ( r = 0.49 , P < 0.05 ) and NHE-1 activity ( r = 0.6 , P < 0.001 ) . The contribution of intraplatelet Ca2 + was attenuated when both parameters were entered in a multivariate regression model . CONCLUSIONS The present study shows a weak , statistically nonsignificant trend towards association of Ca2 + supplementation on 24-h BP in hypertensive subjects with type 2 diabetes . However , our results indicated an interrelation of [Ca2+]i levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes We examined the effect of an outpatient office-based diet and exercise counseling program on weight loss and lipid levels with an onsite dietitian who sees patients at the same visit with the physician and is fully reimbursable . Eighty overweight or obese patients ( average age 55 + /- 12 years , baseline body mass index 30.1 + /- 6.4 kg/m(2 ) ) with > or = 1 cardiovascular risk factor ( 86 % ) or coronary heart disease ( 14 % ) were counseled to exercise 30 minutes/day and eat a modified Dietary Approaches to Stop Hypertension ( DASH ) diet ( saturated fat < 7 % , polyunsaturated fat to 10 % , monounsaturated fat to 18 % , low in glycemic index and sodium and high in fiber , low-fat dairy products , fruits , and vegetables ) . Weight , body mass index , lipid levels , and blood pressure were measured at 1 concurrent follow-up visit with the dietitian and physician and > or = 1 additional follow-up with the physician . Maximum weight lost was an average of 5.6 % ( 10.8 lb ) at a mean follow-up of 1.75 years . Sixty-four ( 81 % ) of these patients maintained significant weight loss ( average weight loss 5.3 % ) at a mean follow-up of 2.6 years . Average decrease in low-density lipoprotein cholesterol was 9.3 % , average decrease in triglycerides was 34 % , and average increase in high-density lipoprotein cholesterol was 9.6 % . Systolic blood pressure was lowered from 129 to 126 mm Hg ( p = 0.21 ) and diastolic blood pressure from 79 to 75 mm Hg ( p = 0.003 ) . In conclusion , having a dietitian counsel patients concurrently with a physician in the outpatient setting is effective in achieving and maintaining weight loss and is fully reimbursable AIMS Blood pressure ( BP ) changes in alcohol-dependent individuals during a 12-week alcohol relapse prevention study were examined in light of drinking status and biomarkers of alcohol consumption [ carbohydrate-deficient transferrin ( % CDT ) and gamma-glutamyl transpeptidase ( GGT ) ] . METHODS Of 160 r and omized alcoholic individuals , 120 who had hypertension and in whom daily drinking data was available , at 6 and 12 weeks of treatment were included . The impact of alcohol consumption on change in systolic BP ( SBP ) and diastolic BP ( DBP ) was examined . Further analysis determined the relationship between BP and alcohol-use biomarkers . RESULTS A significant effect of complete abstinence on both SBP ( -10 mmHg ; P = 0.003 ) and DBP ( -7 mmHg ; P = 0.001 ) when compared to any drinking ( SBP and DBP = -1 mmHg ) was observed . At week 12 , participants with a positive % CDT ( > or = 2.6 ) had 7 mmHg greater SBP ( P = 0.01 ) and DBP ( P < 0.001 ) than those with negative % CDT . Participants with positive GGT ( > or = 50 IU ) had 10 mmHg greater SBP ( P = 0.12 ) and 9 mmHg greater DBP ( P = 0.03 ) than those with negative GGT . The percent change in SBP was correlated with percent change in % CDT ( P = 0.003 ) but not GGT ( P = ns ) . The percent change in DBP was correlated with both percent change in % CDT ( P < 0.0001 ) and GGT ( P = 0.03 ) . CONCLUSIONS Abstinence from alcohol significantly decreased the BP and a positive relationship between BP and both alcohol-use biomarkers was illustrated . Since % CDT is more specific than GGT for heavy alcohol consumption , clinicians may monitor the role of alcohol in hypertension using % CDT as a supplemental aid , providing an objective assessment of drinking to influence BP treatment decisions To determine the effects of potassium supplementation on endothelial function , cardiovascular risk factors , and bone turnover and to compare potassium chloride with potassium bicarbonate , we carried out a 12-week r and omized , double-blind , placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure . Urinary potassium was 77±16 , 122±25 , and 125±27 mmol/24 hours after 4 weeks on placebo , potassium chloride , and potassium bicarbonate , respectively . There were no significant differences in office blood pressure among the 3 treatment periods , and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride . Compared with placebo , both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation , increased arterial compliance as assessed by carotid-femoral pulse wave velocity , decreased left ventricular mass , and improved left ventricular diastolic function . There was no significant difference between the 2 potassium salts in these measurements . The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin : creatinine ratio , and potassium bicarbonate decreased 24-hour urinary calcium , calcium : creatinine ratio , and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly . These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system , and potassium bicarbonate may improve bone health . Importantly , these effects were found in individuals who already had a relatively low-salt and high-potassium intake The relation between parental history of hypertension and blood pressure response to potassium intake is unknown . A 7-day high-sodium followed by a 7-day high-sodium plus potassium dietary-feeding study was conducted from 2003 to 2005 among 1,871 Chinese participants . Those with a maternal history of hypertension had larger systolic blood pressure responses to potassium compared with those without : -4.31 ( 95 % confidence interval ( CI ) : -4.99 , -3.62 ) mm Hg versus -3.35 ( 95 % CI : -4.00 , -2.70 ) mm Hg , respectively ( P(difference ) = 0.002 ) . A consistent trend was observed for diastolic blood pressure responses : -1.80 ( 95 % CI : -2.41 , -1.20 ) mm Hg versus -1.35 ( 95 % CI : -1.95 , -0.74 ) mm Hg , respectively ( P = 0.07 ) . Stronger associations between early onset maternal hypertension and blood pressure responses were noted , with systolic blood pressure decreases of -4.80 ( 95 % CI : -5.65 , -3.95 ) mm Hg versus -3.55 ( 95 % CI : -4.17 , -2.93 ) mm Hg and diastolic blood pressure decreases of -2.25 ( 95 % CI : -3.01 , -1.50 ) mm Hg versus -1.42 ( 95 % CI : -1.99 , -0.85 ) mm Hg among those with early onset maternal hypertension versus those without , respectively ( P = 0.001 and 0.009 , respectively ) . Odds ratios for high potassium sensitivity were 1.36 ( 95 % CI : 0.96 , 1.92 ) and 1.60 ( 95 % CI : 1.08 , 2.36 ) for those with maternal hypertension and early onset maternal hypertension , respectively ( P = 0.08 and 0.02 , respectively ) . Potassium supplementation could help to reduce blood pressure among those with a maternal history of hypertension Low-sodium Dietary Approaches to Stop Hypertension ( DASH ) diets are base producing but restrict red meat without clear justification . We hypothesized that a vitality diet ( VD ) , a low-sodium DASH-type diet with a low dietary acid load containing 6 servings of 100 g cooked lean red meat per week , would be more effective in reducing blood pressure ( BP ) compared with a higher acid load reference healthy diet ( RHD ) based on general dietary guidelines to reduce fat intake and increase intake of breads and cereals . A r and omized , parallel dietary intervention study was conducted to compare the BP-lowering effect of these 2 diets in postmenopausal women with high/normal BP . Women were r and omly assigned to follow either VD or RHD for 14 weeks . Home BP was measured daily with an automated BP monitor under st and ard conditions . Of 111 women commencing the study , 95 completed ( 46 VD , 49 RHD ) . Systolic BP ( SBP ) throughout the intervention was lower in the VD group compared to the RHD group ( repeated- measures analysis of variance time by diet , P = .04 ) , such that at the end of the study , the VD had a fall of SBP by 5.6 + /- 1.3 mm Hg ( mean + /- SEM ) compared with a fall of 2.7 + /- 1.0 mm Hg in the RHD ( group difference , P = .08 ) . When only those taking antihypertensive medications were assessed , the VD ( n = 17 ) had a significant fall of 6.5 + /- 2.5 mm Hg SBP ( P = .02 ) and 4.6 + /- 1.4 mm Hg diastolic BP ( P = .005 ) after 14 weeks , and their BP was lower than that of the RHD group ( n = 18 ) throughout the study ( P < .05 ) . We concluded that a low-sodium DASH diet with a low dietary acid load , which also included lean red meat on most days of the week , was effective in reducing BP in older women , particularly in those taking antihypertensive medications BACKGROUND AND OBJECTIVES Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction . Production of the natriuretic hormone marinobufagenin , an endogenous α1 Na+,K+-ATPase inhibitor , is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The hypothesis was that dietary sodium restriction performed in middle-aged/older adults ( eight men and three women ; 60 ± 2 years ) with moderately elevated systolic BP ( 139 ± 2/83 ± 2 mmHg ) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity ( r and omized , placebo-controlled , and crossover design ) . This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium ( 77 ± 9 mmol/d ) and 5 weeks of a normal-sodium ( 144 ± 7 mmol/d ) diet . RESULTS Urinary marinobufagenin excretion ( weekly measurements ; 25.4 ± 1.8 versus 30.7 ± 2.1 pmol/kg per day ) , systolic BP ( 127 ± 3 versus 138 ± 5 mmHg ) , and aortic pulse-wave velocity ( 700 ± 40 versus 843 ± 36 cm/s ) were lower during the low- versus normal-sodium condition ( all P<0.05 ) . Across all weeks , marinobufagenin excretion was related with systolic BP ( slope=0.61 , P<0.001 ) and sodium excretion ( slope=0.46 , P<0.001 ) . These associations persisted during the normal- but not the low-sodium condition ( both P<0.005 ) . Marinobufagenin excretion also was associated with aortic pulse-wave velocity ( slope=0.70 , P=0.02 ) and endothelial cell expression of NAD(P)H oxidase-p47phox ( slope=0.64 , P=0.006 ) . CONCLUSIONS These results show , for the first time in humans , that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP , aortic stiffness ( aortic pulse-wave velocity ) , and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase . Importantly , marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet , extending previous observations in rodents and humans fed experimentally high-sodium diets Alcohol consumption causes biphasic changes in blood pressure ( BP ) in Asians . The aim of the present study was to investigate the effects of repeated alcohol intake on BP and sodium metabolism . Fourteen Japanese males with hypertension ( 37 - 67 years old ) were examined under st and ardized conditions ( Na intake 120 mmol/day ) . After 1 week of alcohol restriction , the patients consumed a control drink with dinner for 3 days , 1 ml/kg of alcohol for the next 7 days , then the control drink for 3 days . Supine BP and heart rate were measured 5 times daily , and urinary excretion of water and sodium was determined throughout the study period . Average BP decreased initially , then returned to the baseline level during the alcohol period . Evening BP decreased significantly throughout the alcohol period , although the reduction was attenuated during the late phase . Morning and afternoon BP did not change significantly , but tended to be elevated during the late phase . Heart rate increased both in the morning and evening during the alcohol period . Urine volume did not change during the early phase , but increased significantly during the late phase . Urinary sodium excretion decreased initially , but increased during the middle phase of the alcohol period . In conclusion , BP decreases initially with sodium retention , then returns to the baseline level with restoration of sodium balance during repeated alcohol intake in Japanese males with hypertension . Sodium retention during the early phase appears to be the consequence of BP reduction and may contribute to the subsequent changes in BP OBJECTIVES A r and omized clinical trial was used to compare the effects of an angiotensin II type 1 receptor inhibitor , c and esartan , singly or in combination with a reducing sodium diet , the DASH diet , on the quality of life ( QOL ) in out patients with hypertension . METHODS After a 2-week wash out period with placebo , 102 patients with mild to moderate hypertension were r and omly assigned to receive c and esartan ( 8 to 16 mg per day ) , and 99 patients were assigned to follow the DASH diet in addition to the same dose of c and esartan , both for 16 weeks . Patients completed the Subjective Symptoms Assessment Profile question naire , just before treatment and at the end of treatment . ANOVA was used to analyze the QOL-score changes over time and compare treatments . RESULTS Resting blood pressures were significantly reduced by the combination of c and esartan and DASH diet ( p < 0.005 ) . Significant improvement was demonstrated for the mental component scores after 16 weeks of treatment with the combination of c and esartan and DASH diet ( p < 0.03 ) . CONCLUSIONS Angiotensin II type 1 receptor blockade with a therapeutic dosage of c and esartan maintains significant control of blood pressure and may improve QOL-scores , especially when combined with a reducing sodium diet To compare the effect of IV magnesium with other antihypertensives in emergency department ( ED ) patients with hypertension . ED patients with a systolic BP > 135 mmHg or diastolic BP > 85 were approached for entry into the study . Those granting consent were r and omly placed into one of three treatment groups : ( 1 ) 1.5 gm IV MgSO4 ( n = 42 ) , ( 2 ) a parenteral or oral antihypertensive agent ( n = 41 ) , ( 3 ) both IV MgSO4 and an antihypertensive agent ( n = 44 ) . Systolic and diastolic blood pressures were measured at entry into the study and at 15 , 30 , 45 , and 60 min after magnesium or other antihypertensive medications were given . The main outcome measure was blood pressure at 60 min , and results were compared using one-way analysis of variance with the post hoc Tukey HSD test . Compared to systolic and diastolic blood pressures at time 0 , both were lower at 15 , 30 , 45 , and 60 min in all groups ( p < 0.05 ) . No significant difference in systolic or diastolic BP at any time point was observed when response to treatment was compared between the three groups . Intravenous MgSO4 is as effective as antihypertensives at lowering BP in emergency department patients Objective To examine factors related to blood pressure ( BP ) responses to dietary sodium and potassium interventions . Methods We conducted a dietary feeding study that included a 7-day low-salt intervention ( 51.3 mmol sodium/day ) , a 7-day high-salt intervention ( 307.8 mmol sodium/day ) , and a 7-day high-salt and potassium-supplementation ( 60 mmol potassium/day ) intervention among 1906 study participants in rural China . The BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a r and om-zero sphygmomanometer . Results The BP responses to low-sodium intervention were significantly greater in women than in men : −8.1 [ 95 % confidence interval ( −8.6 to −7.6 ) ] versus −7.0 ( −7.5 to −6.6 ) mmHg for systolic and −4.5 ( −4.9 to −4.1 ) versus −3.4 ( −3.8 to −3.0 ) mmHg for diastolic . Likewise , BP responses to high-sodium interventions were significantly greater in women than in men : 6.4 ( 5.9–6.8 ) versus 5.2 ( 4.8–5.7 ) mmHg for systolic and 3.1 ( 2.7–3.5 ) versus 1.7 ( 1.4–2.1 ) mmHg for diastolic ( all P < 0.001 ) . In addition , systolic BP responses to sodium interventions increased with age , and both systolic and diastolic BP responses to sodium interventions increased with baseline BP levels . BP responses to potassium supplementation also increased with baseline BP levels . Conclusion These results suggest that female gender , older age , and hypertension increase the sensitivity to dietary sodium intervention . Furthermore , low dietary sodium intake may be more effective in reducing BP among these subgroups Identifying dietary modifications that potentiate the blood pressure (BP)-lowering effects of antihypertensive medications and that are practical for free-living people may assist in achieving BP reduction goals . We assessed whether two dietary patterns were effective in lowering BP in persons on antihypertensive therapy and in those not on therapy . Ninety-four participants ( 38/56 females/males ) , aged 55·6 ( SD 9·9 ) years , consumed two 4-week dietary regimens in r and om order ( Dietary Approaches to Stop Hypertension (DASH)-type diet and low- Na high-K ( LNAHK ) diet ) with a control diet before each phase . Seated home BP was measured daily for the last 2 weeks in each phase . Participants were grouped based on antihypertensive drug therapy . The LNAHK diet produced a greater fall in systolic BP ( SBP ) in those on antihypertensive therapy ( -6·2 ( SD 6·0 ) mmHg ) than in those not on antihypertensive therapy ( -2·8 ( SD 4·0 ) mmHg ) ( P = 0·036 ) , and this was greatest for those on renin-angiotensin system ( RAS ) blocker therapy ( -9·5 ( SD 6·4 ) mmHg ) ( interaction P = 0·007 ) . The fall in SBP on the DASH-type diet , in those on therapy ( overall -1·1 ( SD 6·2 ) mmHg ; renin-angiotensin blocker therapy -4·2 ( SD 4·7 ) mmHg ) , was not as marked as that observed on the LNAHK diet . Dietary modifications are an important part of all hypertension management regimens , and a low-Na and high-K diet enhances the BP-lowering effect of antihypertensive medications , particularly those targeting the RAS OBJECTIVE To compare the amount of drug quantified by a score needed to control blood pressure in two groups of overweight hypertensive patients , receiving or not receiving a hypocaloric diet . DESIGN R and omized controlled clinical trial . SETTING Two hospital outpatient hypertension clinics . PATIENTS Fifty-four subjects with a DBP between 95 and 110 mmHg and a weight > or = 110 % of the ideal weight . INTERVENTION Allocation to either drug treatment ( DT ) or hypocaloric diet ( HD ) . In the HD group , after 2 months , an antihypertensive drug was administered to the subjects with a DBP > or = 90 mmHg , following the same scheme protocol as in the DT group . Subjects were followed during 10 months by a clinician only in the DT group and by a clinician and a dietician in the HD group . MAIN OUTCOME MEASURES Score of treatment : hydrochlorothiazide 25 mg [ score = 1 ] with , as needed to obtain a DBP < 90 mmHg , the addiction of enalapril 10 mg [ score = 2 ] , 20 mg [ score = 3 ] , and nifedipine 40 mg [ score = 4 ] . RESULTS At the end of the trial , 5 subjects were lost to follow-up in the HD group and 1 in the DT group ( p > 0.05 ) . Mean weight loss was 5.9 kg ( sd = 1.2 ) in the HD and 2.3 kg ( sd = 0.7 ) in the DT group ( p = 0.02 ) . Mean decrease in DBP was 18 mmHg ( sd = 7 ) and 15 mmHg ( sd = 8) in HD and DT groups respectively ( p = 0.36 ) . Mean DBP was 84 mmHg ( sd = 7.8 ) in the HD group and 85 mmHg ( sd = 7.2 ) in the DT group . In the HD group , 8 ( 38.1 % ) subjects had a DBP < 90 mmHg without any drug treatment . The mean drug treatment score was 0.86 ( sd = 0.91 ) in the HD and 1.52 ( 0.70 ) in the DT group ( p = 0.01 ) . CONCLUSION This study shows that in overweight hypertensives , the quantity of drug needed to achieve an acceptable level of BP is nearly reduced by 50 % when an efficient hypocaloric diet is prescribed simultaneously Sodium reduction is efficacious for primary prevention of hypertension , but the feasibility of achieving this effect is unclear . The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention , Phase II . Sodium reduction ( comprehensive education and counselling about how to reduce sodium intake ) was tested vs no dietary intervention ( usual care ) for 36–48 months . A total of 956 white and 203 black adults , ages 30–54 years , with diastolic blood pressure 83–89 mmHg , systolic blood pressure ( SBP ) < 140 mmHg , and body weight 110–165 % of gender-specific st and ard weight were included in the study . At 36 months , urinary sodium excretion was 40.4 mmol/24 h ( 24.4 % ) lower in sodium reduction compared to usual care participants ( P<0.0001 ) , but only 21 % of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts . Net decreases in SBP at 6 , 18 , and 36 months of 2.9 ( P<0.001 ) , 2.0 ( P<0.001 ) , and 1.3 ( P=0.02 ) mmHg in sodium reduction vs usual care were associated with an overall 18 % lower incidence of hypertension ( P=0.048 ) ; were relatively unchanged by adjustment for ethnicity , gender , age , and baseline blood pressure , BMI , and sodium excretion ; and were observed in both black and white men and women . From these beneficial but modest results with highly motivated and extensively counselled individuals , sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure < 90 mm Hg ) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were r and omized into the trial from June 1 , 2009 , through May 31 , 2011 . INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P < .001 ) . No significant treatment effect was seen for mean ( 95 % CI ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858 PURPOSE To characterize relationships between sodium and potassium intakes and blood pressure control . METHODS We analyzed repeated 24-hour diet recalls and 24-hour urine assays from 873 elderly participants with established hypertension in a 3-year clinical trial of lifestyle interventions . Pooled estimates of electrolyte intakes were developed using hierarchical measurement error models and related to nonpharmacologic blood pressure control . RESULTS Relative decreases in sodium and increases in potassium intakes each had grade d relationships with better blood pressure control . After adjustment for measurement error , a 100 mmol/24-hour decrease in sodium intake was associated with an odds ratio of 2.93 [ 95 % confidence interval : 1.83 , 4.64 ] for maintaining nonpharmacologic blood pressure control throughout follow-up . A 50 mmol/24-hour increase in potassium intake was associated with an odds ratio of 2.00 [ 1.12 , 3.55 ] . These relationships were independent of each other and of baseline levels of intakes . Blood pressure control was most strongly associated with sodium intake for participants with lower systolic blood pressures and longer duration of hypertension , and with potassium for those with elevated diastolic blood pressures . CONCLUSIONS Sodium and potassium intakes exert independent grade d influences on nonpharmacologic blood pressure control . Correlated measurement error may spuriously introduce a dependency among these relationships Aim : To investigate the systemic renin-an-giotensin system ( RAS ) in essential hypertensives ( EH ) and controls ( C ) after short- and long-term vitamin D receptor activation . Design : Ten consecutive EH ( under controlled low-salt diet ) and 10 C underwent calcitriol administration ( 0.25 µg bid ) for 1 week ( Group A ) . Eighteen consecutive EH under angiotensin II receptor antagonist therapy received a single oral dose of 300,000 IU of cholecalciferol and were followed up for 8 weeks ( Group B ) . Methods : In basal conditions and at the end of the study ( 1 week in Group A and 8 weeks in Group B ) , plasma renin activity ( PRA ) , plasma active renin , aldosterone , and angiotensin II were evaluated , as well as blood pressure , plasma 25-hy-droxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] , and PTH . Results : In Group A , plasma 25(OH)D levels in EH and C were below the normal range , although lower levels were found in the former . No association between basal plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS components was observed either in the whole group or in the two subgroups . Calcitriol administration did not affect any RAS parameter either in EH or in C. In Group B , cholecalciferol significantly increased 25(OH)D and 1,25(OH)2D levels without interfering with the angiotensin II receptor antagonist-induced increase in RAS components . No correlation was found between plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS parameters before and after cholecalciferol administration . Conclusions : The present data suggest that , in our experimental conditions , vitamin D receptor activation is unable to influence systemic RAS activity Background : Consumption of dairy foods has been associated with lower blood pressure in certain population s. Objective : This study examined the effects of dairy foods on blood pressure ( BP ) and intracellular calcium ( (Ca)i ) and the dependence of BP changes on changes in (Ca)i . Design : Twenty-three stage 1 hypertensive adults were fed the following 3 experimental diets ( 5 wk each ) in a r and omized cross-over design study ; a dairy-rich , high fruits and vegetables diet ( D-F&V ; 30 % fat , 7 % saturated fat ( SFA ) , 3.4 servings/d dairy ) , a high fruits and vegetables diet ( F&V ; 30 % fat , 7 % SFA , 0.4 servings/d dairy ) , and an average Western diet ( control ; 36 % fat , 15 % SFA , 0.4 servings/d dairy ) . Systolic ( SBP ) and diastolic ( DBP ) BP , calcium regulatory hormones , and erythrocyte (Ca)i were determined . Results : SBP and DBP were significantly reduced by ∼2 mm Hg following both D-F&V and F&V diets vs. the control ( P < 0.05 ) . The D-F&V diet significantly lowered 1,25-dihydroxyvitaminD compared with the F&V and control diets ( P < 0.01 ) . Serum calcium , parathyroid hormone , calcitonin , and renin activity were unchanged . The D-F&V diet lowered (Ca)i vs. the other two diets ( P < 0.01 ) , and this change correlated with the fall in DBP ( r = 0.52 , P < 0.05 ) . Subjects who responded to the D-F&V diet by significantly reducing (Ca)i exhibited significantly greater net decreases in DBP on the D-F&V vs. the F&V ( −2.8 ± 1.0 mm Hg ) and control diets ( −5.4 ±1.0 mm Hg ; diet × group interaction , P < 0.02 ) . Conclusion : Consumption of dairy foods beneficially affects (Ca)i , result ing in improved BP in a subgroup defined by (Ca)i response Thirty-five patients with mild to moderate hypertension were r and omised into a three months ' dietary advised and a three months ' control group . The diet was of a composition currently considered to be appropriate , and was monitored by a dietitian . Statistically significant decreases in diastolic blood pressure , mean arterial pressure , sodium excretion , and low density lipoprotein (LDL)-cholesterol occurred in the intervention group , although differences in change between the intervention and the control group were , except for LDL-cholesterol , not statistically significant . Thus , it did not become clear whether and to what extent change in diet was responsible for the lowering of the blood pressure in the intervention group The aim of this study was to compare the differences of dietary and non-dietary factors in hypertension and normal blood pressure ( BP ) of Chinese urban people . Two cross-sectional population surveys were carried out in Tianjin , one of the three largest cities in China . A total of 2068 subjects aged 35–64 years were selected by a r and om stratified cluster sampling , 367 men and 395 women were hypertensive , and 623 men and 683 women had normal BP . The diet was assessed by food weighing plus consecutive individual 3-day food records . Health status , health behaviours and anthropomentry were assessed . The whole population had a high sodium and low potassium consumption level . Hypertensive men and women had significantly higher daily dietary sodium intake ( P < 0.05 ) and hypertensive women had higher dietary sodium-to-potassium ratio ( P < 0.01 ) than men and women with normal BP . Age , body mass index , overweight and family history of hypertension were positively related to high BP . dietary sodium intake and dietary sodium-to-potassium ratio were positively associated with high BP . Education level in women and commuting physical activity in men were inversely associated with high BP Background Higher prevalence of hypertension among African Americans is a key cause of racial disparity in cardiovascular morbidity and mortality . Explanations for the difference in prevalence are incomplete . Emerging data suggest that low vitamin D levels may contribute . Objective To assess the contribution of vitamin D to racial disparity in blood pressure . Design Cross-sectional analysis . Participants Adult non-Hispanic Black and White participants from the National Health and Nutrition Examination Survey 2001–2006 . Measures We assessed Black-White differences in systolic blood pressure ( SBP ) controlling for conventional risk factors , and then additionally , for vitamin D ( serum 25[OH]D ) . Results The sample included 1984 and 5156 Black and White participants ages 20 years and older . The mean age-sex adjusted Black-White SBP difference was 5.2 mm Hg . This difference was reduced to 4.0 mm Hg with additional adjustment for socio-demographic characteristics , health status , health care , health behaviors , and biomarkers ; adding 25(OH)D reduced the race difference by 26 % ( 95 % CI 7–46 % ) to 2.9 mm Hg . This effect increased to 39 % ( 95 % CI 14–65 % ) when those on antihypertensive medications were excluded . Supplementary analyses that controlled for cardiovascular fitness , percent body fat , physical activity monitoring , skin type and social support yielded consistent results . Conclusion In cross-sectional analyses , 25(OH)D explains one quarter of the Black-White disparity in SBP . R and omized controlled trials are required to determine whether vitamin D supplementation could reduce racial disparity in BP Objectives To examine the effect of spinal manipulation on blood pressure . Design This r and omized clinical trial compared the effects of chiropractic spinal manipulation and diet with diet alone for lowering blood pressure in participants with high-normal blood pressure or stage I hypertension . Blood pressure observers were blinded to treatment group . Setting The study was conducted at the Berman Center for Clinical and Outcomes Research in Minnesota . Chiropractic treatments were administered by chiropractic physicians within private practice setting s. Participants One hundred and forty men and women , aged 25–60 years , with high-normal blood pressure or stage I hypertension , were enrolled . One hundred and twenty-eight participants completed the study . Interventions ( i ) A dietary intervention program administered by a dietitian or ( ii ) a dietary intervention program administered by a doctor of chiropractic in conjunction with chiropractic spinal manipulation . The frequency of treatment for both groups was three times per week for 4 weeks , for a total of 12 visits . Main outcome measures The primary outcomes for this study were change from baseline in diastolic and systolic blood pressure . Results Study groups were comparable at baseline . Changes in potentially confounding covariates did not differ between groups . Average decreases in systolic/diastolic blood pressure were −4.9/5.6 mmHg for diet group and −3.5/4.0 mmHg for the chiropractic group . Between group changes were not statistically significant . Conclusions For patients with high normal blood pressure or stage I hypertension , chiropractic spinal manipulation in conjunction with a dietary modification program offered no advantage in lowering either diastolic or systolic blood pressure compared to diet alone BACKGROUND Prevalence of hypertension is greater in older adults , and increased intake of fruits , vegetables , and dairy-good sources of potassium , calcium , and magnesium-can reduce blood pressure . This study examined the hypertension-related dietary patterns of older adults . METHODS A cohort of 180 Pennsylvania adults ( aged > /=65 ) , 90 with hypertension , were r and omly selected from the Geisinger Rural Aging Study ( GRAS ) . Data were collected by trained interviewers at a home visit . Dietary assessment used five 24-h recalls . We compared the characteristics and dietary intake of people with hypertension to those without hypertension and compared their intakes to current recommendations . RESULTS Mean intakes of all participants were less than two thirds of the DRI for calcium and magnesium and fell far short of the 3,500 mg of potassium recommended for prevention and treatment of hypertension . Participants with hypertension consumed less sodium than controls . Both groups ate fewer fruits and vegetables than recommended but reached the dairy recommendation . Calcium intake was mainly from high-fat dairy products , beans were the top source of potassium and magnesium . CONCLUSIONS Older adults with hypertension should be guided to choose more low-fat dairy products and other low-fat calcium sources and to increase intakes of beans , dark green leafy vegetables , and other potassium and magnesium sources CONTEXT Weight loss , sodium reduction , increased physical activity , and limited alcohol intake are established recommendations that reduce blood pressure ( BP ) . The Dietary Approaches to Stop Hypertension ( DASH ) diet also lowers BP . To date , no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations . OBJECTIVE To determine the effect on BP of 2 multicomponent , behavioral interventions . DESIGN , SETTING , AND PARTICIPANTS R and omized trial with enrollment at 4 clinical centers ( January 2000-June 2001 ) among 810 adults ( mean [ SD ] age , 50 [ 8.9 ] years ; 62 % women ; 34 % African American ) with above-optimal BP , including stage 1 hypertension ( 120 - 159 mm Hg systolic and 80 - 95 mm Hg diastolic ) , and who were not taking antihypertensive medications . INTERVENTION Participants were r and omized to one of 3 intervention groups : ( 1 ) " established , " a behavioral intervention that implemented established recommendations ( n = 268 ) ; ( 2 ) " established plus DASH,"which also implemented the DASH diet ( n = 269 ) ; and ( 3 ) an " advice only " comparison group ( n = 273 ) . MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months . RESULTS Both behavioral interventions significantly reduced weight , improved fitness , and lowered sodium intake . The established plus DASH intervention also increased fruit , vegetable , and dairy intake . Across the groups , gradients in BP and hypertensive status were evident . After subtracting change in advice only , the mean net reduction in systolic BP was 3.7 mm Hg ( P<.001 ) in the established group and 4.3 mm Hg ( P<.001 ) in the established plus DASH group ; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg ( P = .43 ) . Compared with the baseline hypertension prevalence of 38 % , the prevalence at 6 months was 26 % in the advice only group , 17 % in the established group ( P = .01 compared with the advice only group ) , and 12 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .12 compared with the established group ) . The prevalence of optimal BP ( < 120 mm Hg systolic and < 80 mm Hg diastolic ) was 19 % in the advice only group , 30 % in the established group ( P = .005 compared with the advice only group ) , and 35 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .24 compared with the established group ) . CONCLUSION Individuals with above-optimal BP , including stage 1 hypertension , can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk BACKGROUND Dietary habits are associated with obesity , and both are important contributing factors to lifestyle-related diseases . The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals ( UMIN Registration No : 000006582 ) . METHODS AND RESULTS Two-hundred adult patients with hypertension and /or diabetes mellitus were r and omly divided into 2 groups with/without dietary counseling and consumed an ordinary diet for 4 weeks . Each group was then subdivided into 2 groups with/without dietary counseling and received calorie-controlled lunch and dinner boxes for the next 4 weeks . The calories in the delivered meals were based on the subject 's ideal body weight ( BW ) and physical activity level . BW , waist circumference , blood pressure , and laboratory data , including glycoalbumin , were measured at 0 , 4 , and 8 weeks . BW and the other parameters were significantly reduced during the study period in patients who received diet counseling in the ordinary diet period and /or delivered meal period but not in patients without dietary counseling , as assessed by linear mixed models for longitudinal data . CONCLUSIONS The combination of dietary counseling by dietitians and delivery of calorie-controlled meals was effective in reducing BW , as well as blood pressure and glycoalbumin , in patients with hypertension and /or diabetes mellitus Context Can adults make sustained changes in unhealthy lifestyle behaviors ? Content In this multicenter trial , 810 adult volunteers with prehypertension or stage 1 hypertension were r and omly assigned to a multicomponent behavioral intervention group , a group combining the behavioral intervention plus the Dietary Approaches to Stop Hypertension ( DASH ) diet , or an advice only group . At 18 months , participants in both behavioral intervention groups had less hypertension , more weight loss , and better reduction in sodium and fat intake than those receiving advice only . The participants in the DASH diet group also increased their intake of fruits , vegetables , and fiber . Implication s Motivated adults can sustain several lifestyle changes over 18 months , which might reduce their risk for cardiovascular disease . The Editors The public health burden of chronic diseases related to suboptimal diet and physical inactivity is enormous . It has been estimated that these lifestyle factors contribute to approximately 20 % of deaths in the United States ( 1 ) . Incidence of atherosclerotic cardiovascular disease , overweight and obesity , elevated blood pressure and lipid levels , diabetes , osteoporosis , and cancer is increased by unhealthy lifestyles ( 2 - 8 ) . Multiple lifestyle factors , such as physical inactivity ; excessive intake of calories , sodium , saturated fat , and cholesterol ; and inadequate intake of fruits , vegetables , and low-fat dairy products , are etiologically related to the development of these diseases ( 4 , 5 , 8 - 10 ) . To reduce the burden of chronic disease , increased physical activity and changes in diet are needed , yet few intervention studies have attempted to achieve many lifestyle changes simultaneously . The PREMIER r and omized trial tested the effects of 2 multicomponent behavioral interventions on blood pressure ( 11 ) . Both interventions promoted increased physical activity , weight loss , and reduced sodium intake , each of which is recommended by the 2005 Dietary Guidelines Scientific Advisory Committee ( 12 ) . One intervention also added the Dietary Approaches to Stop Hypertension ( DASH ) diet ( 13 ) . This diet , which is high in fruits , vegetables , and low-fat dairy products and low in saturated fat , total fat , and cholesterol , meets each of the major nutrient recommendations that were established by the Institute of Medicine ( 14 - 18 ) . We report the effects of the PREMIER interventions on lifestyle changes and blood pressure status at 18 months . The main results of PREMIER , namely change in blood pressure at 6 months , were reported previously ( 11 ) . Methods The PREMIER study design and rationale ( 19 ) and intervention methods ( 11 ) have been described previously . The institutional review boards at each clinical center ; an external protocol review committee appointed by the National Heart , Lung , and Blood Institute ( NHLBI ) ; and the NHLBI review ed and approved the protocol ( available at www.kpchr.org/public/premier/intervention/default.asp ) . The NHLBI also appointed a data and safety monitoring board to monitor the trial . Each participant provided written informed consent . The trial was conducted from January 2000 through November 2002 . Study Participants Participants were generally healthy adults , age 25 years or older , who had prehypertension or stage 1 hypertension and met the Joint National Committee VI ( JNC VI ) criteria for a 6-month trial of nonpharmacologic therapy ( 2 ) . Targeted recruitment methods were used to ensure adequate representation of clinical ly important subgroups , in particular , African-American persons . Specific methods varied from site to site but included direct mailings , radio and newspaper advertisements , and networking within the local African-American communities . Eligibility criteria included not taking antihypertensive medication and having a systolic blood pressure of 120 to 159 mm Hg and a diastolic blood pressure of 80 to 95 mm Hg , based on the average of 3 screening visits . Persons with prehypertension ( systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg ) were included because of the excess risk for cardiovascular disease in those with blood pressure within this range ( 20 ) . Major exclusion criteria were a body mass index less than 18.5 kg/mg2 or greater than 45.0 kg/m2 , use of antihypertensive drugs or other drugs that affect blood pressure , JNC VI risk category C ( target organ damage or diabetes ) , use of prescription weight loss medications , previous cardiovascular event , congestive heart failure , angina , cancer , and consumption of more than 21 alcoholic drinks per week . Trial Conduct Eligible participants were r and omly assigned , with equal probability , to 1 of 3 groups : an advice only comparison group ( advice only ) ; an intervention group that targeted established , guideline -recommended lifestyle recommendations ( established ) ( 2 ) ; or an intervention group targeting the established recommendations and adding the DASH dietary pattern ( established plus DASH ) ( 13 ) . Computer-generated treatment assignments were stratified by clinic and hypertension status and were assigned in blocks of varying sizes to provide balance over time . The actual assignments were administered by using a password-protected , Web-based application developed by the coordinating center and accessible only by authorized individuals . All clinic measurement staff were blinded to treatment assignment , and all intervention staff were blinded to clinic measurements . Hypertension was defined by using the JNC VI criteria for hypertension treatment : an average systolic blood pressure of 140 mm Hg , a diastolic blood pressure greater than 90 mm Hg , or use of antihypertensive medication . Normal blood pressure was defined as systolic blood pressure less than 120 mm Hg , diastolic blood pressure less than 80 mm Hg , and no use of antihypertensive medication ( 21 ) ( Figure ) . Intervention was provided by master 's degreelevel counselors ( dietitians and health educators trained in behavioral methods ) . The counselors were central ly trained before the start of the study , attended annual 3-day training sessions , and participated in monthly conference calls . Figure . Flow diagram of enrollment , measurements , and visit completion . Advice Only Group Participants in the advice group received advice to follow the National High Blood Pressure Education Program lifestyle recommendations for blood pressure control ( 2 ) . Lifestyle recommendations included reducing weight ( if overweight ) , following a reduced-sodium diet , engaging in regular moderate-intensity physical activity , and eating a heart-healthy diet , including the DASH diet . This advice was provided in two 30-minute individual sessions , 1 immediately after r and om assignment and 1 after the 6-month data collection visit . A PREMIER counselor review ed the guidelines with the participant and provided printed educational material s and information about community re sources . This intervention did not include advice to keep a food or exercise diary . Behavioral Interventions in the Established and Established plus DASH Groups Participant goals for the established and established plus DASH groups included weight loss of at least 6.8 kg ( 15 lb ) for those with a body mass index of 25 kg/m2 or greater , at least 180 minutes per week of moderate-intensity physical activity , no more than 100 mmol per day of dietary sodium , and alcohol consumption of no more than 30 mL ( 1 oz ) per day ( 2 drinks ) for men and 15 mL ( 0.5 ) oz per day ( 1 drink ) for women . Participants assigned to the established plus DASH group ( but not those in the established group ) also received counseling on the DASH diet , with goals for increased consumption of fruits and vegetables ( 9 to 12 servings/d ) and low-fat dairy products ( 2 to 3 servings/d ) and reduced consumption of saturated fat ( 7 % of energy ) and total fat ( 25 % of energy ) . The intervention format , contact pattern , and behavior change strategies for the established and established plus DASH groups were identical . During the first 6 months , participants in both behavioral intervention groups attended 14 group sessions and 4 individual sessions ; during months 7 to 18 , they attended monthly group sessions supplemented with 3 individual counseling sessions . Throughout the trial , participants in the established and established plus DASH groups ( but not those in the advice group ) kept food diaries , monitored dietary calorie and sodium intakes , and recorded minutes of physical activity . Self-monitoring was used to provide individualized feedback , reinforcement , problem solving , and support . Social support for initial behavior changes and maintenance of change was provided during the group sessions . More detailed descriptions of the behavorial intervention methods are available ( 22 ) . Measurements Blood pressure was assessed twice at each measurement , and systolic and diastolic blood pressures were calculated by using the mean of all available measurements ( 4 sets before r and om assignment , 3 sets at 6 and 18 months , and 1 set at 3 and 12 months ) . For 4 participants who were started on antihypertensive drug therapy between the 12- and 18-month visits , we obtained an official set of blood pressure measurements before initiation of therapy and used these as our 18-month blood pressure values for analysis . A similar procedure was used to obtain the 6-month blood pressure value for the 1 participant who began taking antihypertensive drugs between the 3- and 6-month visits . Two 24-hour dietary recalls , 1 obtained on a weekday and the other obtained on a weekend , were collected at baseline and at 6 and 18 months by telephone interview ( 23 ) . Intakes of nutrients and food groups were calculated by using the Nutrition Data System for Research , version NDS-R 1998 ( University of Minnesota , Minneapolis , Minnesota ) . Urinary excretion of sodium ( reflecting salt intake ) and potassium ( reflecting fruit and vegetable intake ) was obtained from 24-hour urinary collection s at baseline BACKGROUND Accumulating evidence implicates a role of Mg(2 + ) in the pathophysiology of essential hypertension . Previous studies evaluating the antihypertensive efficacy of Mg(2 + ) supplementation gave contradictory results . This study aim ed to investigate the effect of oral Mg(2 + ) supplementation on 24-h blood pressure ( BP ) and intracellular ion status in patients with mild hypertension . METHODS A total of 48 patients with mild uncomplicated hypertension participated in the study . Among them , 24 subjects were assigned to 600 mg of pidolate Mg(2 + ) daily in addition to lifestyle recommendations for a 12-week period and another 24 age- and sex-matched controls were only given lifestyle recommendations . At baseline and study -end ( 12 weeks ) ambulatory BP monitoring , determination of serum and intracellular ion levels , and 24-h urinary collection s for determination of urinary Mg(2 + ) were performed in all study subjects . RESULTS In the Mg(2 + ) supplementation group , small but significant reductions in mean 24-h systolic and diastolic BP levels were observed , in contrast to control group ( -5.6 + /- 2.7 vs. -1.3 + /- 2.4 mm Hg , P < 0.001 and -2.8 + /- 1.8 vs. -1 + /- 1.2 mm Hg , P = 0.002 , respectively ) . These effects of Mg(2 + ) supplementation were consistent in both daytime and night-time periods . Serum Mg(2 + ) levels and urinary Mg(2 + ) excretion were significantly increased in the intervention group . Intracellular Mg(2 + ) and K(+ ) levels were also increased , while intracellular Ca(2 + ) and Na(+ ) levels were decreased in the intervention group . None of the intracellular ions were significantly changed in the control group . CONCLUSION This study suggests that oral Mg(2 + ) supplementation is associated with small but consistent ambulatory BP reduction in patients with mild hypertension Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient Objective Alcohol is associated with acute increases in muscle sympathetic nerve activity ( MSNA ) in normal individuals . The effects of alcohol on MSNA in patients with hypertension are unknown . Using a r and omized , placebo-controlled study design , we tested the hypothesis that there is a differential effect of acute alcohol consumption on cardiovascular function in hypertensive patients compared with normotensive controls . Methods We examined the effects of oral alcohol intake ( 1.0 g/kg body weight ) and placebo on blood pressure , heart rate , and MSNA in 13 newly diagnosed hypertensive patients and 11 normotensive controls . The two sessions were performed in r and om order , each study on a separate day . Results Baseline MSNA was significantly elevated in the hypertensive patients as compared to the controls ( 38 ± 2 vs. 28 ± 2 bursts/min ; P < 0.01 ) . Placebo had no significant effect on MSNA , blood pressure , or heart rate in either group . In normotensive individuals , alcohol had no significant effect on blood pressure ( SBP increased by 1 ± 4 mmHg ) . By contrast , SBP increased after alcohol in hypertensive patients by 24 ± 6 mmHg ( P < 0.001 vs. controls ) . MSNA increased after alcohol in controls by 83 ± 34 % ( P < 0.01 vs. baseline ) . MSNA did not change significantly after alcohol in hypertensive patients ( 16 ± 7 % , not significant ) , despite a profound blood pressure increase , which would be expected to inhibit sympathetic activity . Conclusion Pressor responses to acute alcohol consumption are potentiated in hypertensive patients compared with normotensive controls . Vasoconstrictor sympathetic tone is not suppressed in hypertensive patients after alcohol , despite the enhanced pressor response . Sympathetic neural mechanisms might contribute to both alcohol-related blood pressure increases and cardiovascular events in hypertensive patients The authors investigated the efficacy of a lifestyle educational program , organized in small group meetings , in improving the outcome of a nonpharmacologic intervention . One hundred and eighty-eight hypertensive patients with stable blood pressure ( BP ) levels and drug therapy in the previous 6 months were r and omly divided into educational care ( EC ) and usual care ( UC ) groups . They were followed at 3-month intervals up to 2 years . In addition to the visits in an outpatient clinic , patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment . At baseline , EC and UC groups were similar for age , sex , body mass index ( BMI ) , blood pressure ( BP ) levels , and pharmacologic treatment . Patients in the EC group had significantly reduced total energy , total and saturated fats , and sodium intake . Physical activity was significantly increased in the EC group as well . At the end of the 1-year follow-up , BMI ( P<.001 ) , visceral fat ( P<.001 ) , and BP ( P<.001 ) were significantly lower in the EC group compared with the UC group . Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study |
525 | 18,579,832 | Concluding , it seems that electronic prescribing can reduce the risk for medication errors and ADE . | The objective of this systematic review is to analyse the relative risk reduction on medication error and adverse drug events ( ADE ) by computerized physician order entry systems ( CPOE ) . | OBJECTIVE Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit ( PICU ) . METHODS We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospect ively during a 6-month control and a 6-month intervention period . M and atory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via question naire . RESULTS The rate of pharmacy interventions for erroneous drug doses declined by 59 % . The rate of anti-infective subtherapeutic patient days decreased by 36 % , and the rate of excessive-dose days declined by 28 % . The number of orders placed per antiinfective course decreased 11.5 % , and the robust estimate of the antiinfective costs per patient decreased 9 % . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar , as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders , improved therapeutic dosage targets , and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents , decision support systems , drug therapy , medication errors , child , infant BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions BACKGROUND Medication errors are common , and while most such errors have little potential for harm they cause substantial extra work in hospitals . A small proportion do have the potential to cause injury , and some cause preventable adverse drug events . OBJECTIVE To evaluate the impact of computerized physician order entry ( POE ) with decision support in reducing the number of medication errors . DESIGN Prospect i ve time series analysis , with four periods . SETTING AND PARTICIPANTS All patients admitted to three medical units were studied for seven to ten-week periods in four different years . The baseline period was before implementation of POE , and the remaining three were after . Sophistication of POE increased with each successive period . INTERVENTION Physician order entry with decision support features such as drug allergy and drug-drug interaction warnings . MAIN OUTCOME MEASURE Medication errors , excluding missed dose errors . RESULTS During the study , the non-missed-dose medication error rate fell 81 percent , from 142 per 1,000 patient-days in the baseline period to 26.6 per 1,000 patient-days in the final period ( P < 0.0001 ) . Non-intercepted serious medication errors ( those with the potential to cause injury ) fell 86 percent from baseline to period 3 , the final period ( P = 0.0003 ) . Large differences were seen for all main types of medication errors : dose errors , frequency errors , route errors , substitution errors , and allergies . For example , in the baseline period there were ten allergy errors , but only two in the following three periods combined ( P < 0.0001 ) . CONCLUSIONS Computerized POE substantially decreased the rate of non-missed-dose medication errors . A major reduction in errors was achieved with the initial version of the system , and further reductions were found with addition of decision support features BACKGROUND Physicians frequently need to start antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . We developed and evaluated a computerized antibiotic consultant to assist physicians in the selection of appropriate empiric antibiotics . METHODS We used a two-stage r and om- selection study to compare antibiotics suggested by the antibiotic consultant with 482 associated antibiotic susceptibility results and the concurrent antibiotics ordered by physicians . The antibiotics ordered by r and omized physicians were then compared between crossover periods of antibiotic consultant use . RESULTS The antibiotic consultant suggested an antibiotic regimen to which all isolated pathogens were shown to be susceptible for 453 ( 94 % ) of 482 culture results , while physicians ordered an antibiotic regimen to which all isolated pathogens were susceptible for 369 culture results ( 77 % ) ( P < .001 ) . The physicians who prescribed antibiotics to which all pathogens were susceptible did so a mean of 21 hours after the culture specimens were collected . Physicians ordered appropriate antibiotics within 12 hours of the culture collection significantly more often when they had use of the antibiotic consultant than during the period before use ( P < .035 ) . Moreover , 88 % of the physicians stated they would recommend the program to other physicians , 85 % said the program improved their antibiotic selection , and 81 % said they felt use of the program improved patient care . CONCLUSIONS Information from computer-based medical records can be used to help improve physicians ' selection of empiric antibiotics for infections Introduction Medication errors in the intensive care unit ( ICU ) are frequent and lead to attributable patient morbidity and mortality , increased length of ICU stay and substantial extra costs . We investigated if the introduction of a computerized ICU system ( Centricity Critical Care Clinisoft , GE Healthcare ) reduced the incidence and severity of medication prescription errors ( MPEs ) . Methods A prospect i ve trial was conducted in a paper-based unit ( PB-U ) versus a computerized unit ( C-U ) in a 22-bed ICU of a tertiary university hospital . Every medication order and medication prescription error was vali date d by a clinical pharmacist . The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines . An independent panel evaluated the severity of MPEs . We identified three groups : minor MPEs ( no potential to cause harm ) ; intercepted MPEs ( potential to cause harm but intercepted on time ) ; and serious MPEs ( non-intercepted potential adverse drug events ( ADE ) or ADEs , being MPEs with potential to cause , or actually causing , patient harm ) . Results The C-U and the PB-U each contained 80 patient-days , and a total of 2,510 medication prescriptions were evaluated . The clinical pharmacist identified 375 MPEs . The incidence of MPEs was significantly lower in the C-U compared with the PB-U ( 44/1286 ( 3.4 % ) versus 331/1224 ( 27.0 % ) ; P < 0.001 ) . There were significantly less minor MPEs in the C-U than in the PB-U ( 9 versus 225 ; P < 0.001 ) . Intercepted MPEs were also lower in the C-U ( 12 versus 46 ; P < 0.001 ) , as well as the non-intercepted potential ADEs ( 21 versus 48 ; P < 0.001 ) . There was also a reduction of ADEs ( 2 in the C-U versus 12 in the PB-U ; P < 0.01 ) . No fatal errors occurred . The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups . Patients with renal failure experienced less dosing errors in the C-U versus the PB-U ( 12 versus 35 serious MPEs ; P < 0.001 ) . Conclusion The ICU computerization , including the medication order entry , result ed in a significant decrease in the occurrence and severity of medication errors in the ICU Introduction The study aim ed to compare the impact of computerised physician order entry ( CPOE ) without decision support with h and -written prescribing ( HWP ) on the frequency , type and outcome of medication errors ( MEs ) in the intensive care unit . Methods Details of MEs were collected before , and at several time points after , the change from HWP to CPOE . The study was conducted in a London teaching hospital 's 22-bedded general ICU . The sampling periods were 28 weeks before and 2 , 10 , 25 and 37 weeks after introduction of CPOE . The unit pharmacist prospect ively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods , during the course of his normal chart review . Results The total proportion of MEs was significantly lower with CPOE ( 117 errors from 2429 prescriptions , 4.8 % ) than with HWP ( 69 errors from 1036 prescriptions , 6.7 % ) ( p < 0.04 ) . The proportion of errors reduced with time following the introduction of CPOE ( p < 0.001 ) . Two errors with CPOE led to patient harm requiring an increase in length of stay and , if administered , three prescriptions with CPOE could potentially have led to permanent harm or death . Differences in the types of error between systems were noted . There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined ( p = 0.01 ) . The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods ( 19.4 versus 20.0 , respectively , p = 0.71 ) . Conclusion Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score ( if intercepted errors were included ) . Moderate and major errors , however , remain a significant concern with CPOE CONTEXT Adverse drug events ( ADEs ) are a significant and costly cause of injury during hospitalization . OBJECTIVES To evaluate the efficacy of 2 interventions for preventing nonintercepted serious medication errors , defined as those that either result ed in or had potential to result in an ADE and were not intercepted before reaching the patient . DESIGN Before-after comparison between phase 1 ( baseline ) and phase 2 ( after intervention was implemented ) and , within phase 2 , a r and omized comparison between physician computer order entry ( POE ) and the combination of POE plus a team intervention . SETTING Large tertiary care hospital . PARTICIPANTS For the comparison of phase 1 and 2 , all patients admitted to a stratified r and om sample of 6 medical and surgical units in a tertiary care hospital over a 6-month period , and for the r and omized comparison during phase 2 , all patients admitted to the same units and 2 r and omly selected additional units over a subsequent 9-month period . INTERVENTIONS A physician computer order entry system ( POE ) for all units and a team-based intervention that included changing the role of pharmacists , implemented for half the units . MAIN OUTCOME MEASURE Nonintercepted serious medication errors . RESULTS Comparing identical units between phases 1 and 2 , nonintercepted serious medication errors decreased 55 % , from 10.7 events per 1000 patient-days to 4.86 events per 1000 ( P=.01 ) . The decline occurred for all stages of the medication-use process . Preventable ADEs declined 17 % from 4.69 to 3.88 ( P=.37 ) , while nonintercepted potential ADEs declined 84 % from 5.99 to 0.98 per 1000 patient-days ( P=.002 ) . When POE-only was compared with the POE plus team intervention combined , the team intervention conferred no additional benefit over POE . CONCLUSIONS Physician computer order entry decreased the rate of nonintercepted serious medication errors by more than half , although this decrease was larger for potential ADEs than for errors that actually result ed in an ADE OBJECTIVE Medication errors are a major concern of health care professionals and medical institutions , especially errors involving children . Studies in adults have shown that computerized physician order entry ( CPOE ) systems reduce medication errors and adverse drug events ( ADEs ) . The effect of CPOE implementation in a pediatric population has not been reported . The objective of this study was to evaluate the impact of CPOE on the frequency of errors in the medication ordering process in a pediatric critical care unit ( PCCU ) . METHODS A prospect i ve trial was conducted of 514 pediatric patients who were admitted to a 20-bed PCCU in a tertiary-care children 's hospital before and after implementation of CPOE . Medication errors were identified after review of all orders during the study period and then further classified as potential ADEs , medication prescribing errors ( MPE ) , and rule violations ( RV ) . RESULTS A total of 13 828 medication orders were review ed . Before implementation , potential ADEs occurred at a rate of 2.2 per 100 orders , MPEs at a rate of 30.1 per 100 orders , and RVs at a rate of 6.8 per 100 orders . After implementation , the rate of potential ADEs was reduced to 1.3 per 100 orders , MPEs to 0.2 per 100 orders , and RVs to 0.1 per 100 orders . The overall error reduction was 95.9 % . Potential ADEs were reduced by 40.9 % , and MPEs and RVs were reduced by 99.4 % and 97.9 % , respectively . CONCLUSIONS The implementation of CPOE result ed in almost a complete elimination of MPEs and RVs and a significant but less dramatic effect on potential ADEs Abstract BACKGROUND : Medication errors are common among in patients and many are preventable with computerized prescribing . Relatively little is known about outpatient prescribing errors or the impact of computerized prescribing in this setting . OBJECTIVE : To assess the rates , types , and severity of outpatient prescribing errors and underst and the potential impact of computerized prescribing . DESIGN : Prospect i ve cohort study in 4 adult primary care practice s in Boston using prescription review , patient survey , and chart review to identify medication errors , potential adverse drug events ( ADEs ) and preventable ADEs . PARTICIPANTS : Out patients over age 18 who received a prescription from 24 participating physicians . RESULTS : We screened 1879 prescriptions from 1202 patients , and completed 661 surveys ( response rate 55 % ) . Of the prescriptions , 143 ( 7.6 % ; 95 % confidence interval ( CI ) 6.4 % to 8.8 % ) contained a prescribing error . Three errors led to preventable ADEs and 62 ( 43 % ; 3 % of all prescriptions ) had potential for patient injury ( potential ADEs ) ; I was potentially life-threatening ( 2 % ) and 15 were serious ( 24 % ) . Errors in frequency ( n=77 , 54 % ) and dose ( n=26 , 18 % ) were common . The rates of medication errors and potential ADEs were not significantly different at basic computerized prescribing sites ( 4.3 % vs 11.0 % , P=.31 ; 2.6 % vs 4.0 % , P=.16 ) compared to h and written sites . Advanced checks ( including dose and frequency checking ) could have prevented 95 % of potential ADEs . CONCLUSIONS : Prescribing errors occurred in 7.6 % of outpatient prescriptions and many could have harmed patients . Basic computerized prescribing systems may not be adequate to reduce errors . More advanced systems with dose and frequency checking are likely needed to prevent potentially harmful errors Abstract Background and objective : Medication errors are an important cause of hospital-based morbidity and mortality . However , only a few medication error studies have been conducted in children . These have mainly quantified errors in the inpatient setting ; there is very little data available on paediatric outpatient and emergency department medication errors and none on discharge medication . This deficiency is of concern because medication errors are more common in children and it has been suggested that the risk of an adverse drug event as a consequence of a medication error is higher in children than in adults . Objective : The aims of this study were to assess the rate of medication errors in predominantly ambulatory paediatric patients and the effect of computer calculated doses on medication error rates of two commonly prescribed drugs . Methods : This was a prospect i ve cohort study performed in a paediatric unit in a university teaching hospital between March 2003 and August 2003 . The hospital ’s existing computer clinical decision support system was modified so that doctors could choose the traditional prescription method or the enhanced method of computer calculated dose when prescribing paracetamol ( acetaminophen ) or promethazine . All prescriptions issued to children ( < 16 years of age ) at the outpatient clinic , emergency department and at discharge from the inpatient service were analysed . A medication error was defined as to have occurred if there was an underdose ( below the agreed value ) , an overdose ( above the agreed value ) , no frequency of administration specified , no dose given or excessive total daily dose . The medication error rates and the factors influencing medication error rates were determined using SPSS version 12 . Results : From March to August 2003 , 4281 prescriptions were issued . Seven prescriptions ( 0.16 % ) were excluded , hence 4274 prescriptions were analysed . Most prescriptions were issued by paediatricians ( including neonatologists and paediatric surgeons ) and /or junior doctors . The error rate in the children ’s emergency department was 15.7 % , for out patients was 21.5 % and for discharge medication was 23.6 % . Most errors were the result of an underdose ( 64 % ; 536/833 ) . The computer calculated dose error rate was 12.6 % compared with the traditional prescription error rate of 28.2 % . Logistical regression analysis showed that computer calculated dose was an important and independent variable influencing the error rate ( adjusted relative risk = 0.436 , 95 % CI 0.336 , 0.520 , p < 0.001 ) . Other important independent variables were seniority and paediatric training of the person prescribing and the type of drug prescribed . Conclusions : Medication error , especially underdose , is common in outpatient , emergency department and discharge prescriptions . Computer calculated doses can significantly reduce errors , but other risk factors have to be concurrently addressed to achieve maximum benefit Physicians ' decisions control between 70 % and 80 % of all health care dollars spent [ 1 - 3 ] , and many strategies to influence or control physician decision making have been advocated . These strategies include education , peer review with feedback , administrative interventions , financial incentives and penalties , critical pathways , and , most recently , nationally derived guidelines [ 2 , 4 ] . To date , none of these strategies has been clearly effective [ 4 ] . Berwick [ 5 ] has outlined the inherent flaws in many of these strategies . He concedes that these methods may lead to predictable care but notes that they can not lead to continual improvement of care . Nowhere in health care are these strategies to control or influence physicians more prevalent than in the area of drug use , particularly use of antimicrobial agents [ 6 ] . The hospital-wide use of drugs and the involvement of various health care providers create a system of diffuse responsibility , enormous variation , and escalating costs [ 6 - 9 ] . The United States currently spends $ 40 billion annually on pharmaceuticals ; this is 8 % of the total cost of health care [ 3 , 7 - 9 ] . Prescription drugs now constitute between 5 % and 20 % of an individual hospital 's total budget [ 7 ] . Antimicrobial agents are one of the costliest categories of drug expenditures in hospitals , accounting for approximately 20 % to 50 % of total spending on drugs [ 9 - 14 ] . Investigations in various clinical practice setting s have indicated that as much as 50 % of antibiotic use is inappropriate [ 14 - 17 ] . The consequences of this have been addressed in terms of antimicrobial resistance [ 18 , 19 ] , adverse drug reactions [ 15 , 17 ] , and cost [ 11 - 14 ] . In response to these pressures , professional societies and individual investigators have outlined methods with which to improve antibiotic use [ 20 - 29 ] . Most of these methods ( for example , drug formularies ) use some form of a control mechanism , and , to date , experience with them has been mixed [ 11 , 16 , 25 , 27 , 28 ] . Kassirer [ 30 ] has challenged the health care system to develop strategies that inform rather than enforce or control medical decisions . For more than a decade , we have been developing and investigating clinical management programs that augment and inform clinical decision making , in addition to focusing on continual quality improvement [ 31 , 32 ] , in antibiotic therapy , infection control surveillance , and the safety of drug use . These programs were design ed to provide continuous surveillance and computer-assisted decision support [ 33 , 34 ] to all clinicians responsible for inpatient care in a general hospital . The hallmark of these computer-assisted decision support programs was local clinician-derived consensus practice guidelines [ 5 , 31 , 34 , 35 ] that were programmed into a hospital information system as rules , algorithms , and predictive models . These programs managed antibiotic use at three basic levels : prophylactic use , empiric use , and therapeutic use . We review the clinical and process outcomes and the financial effects of these hospital-wide decision support programs during a 7-year period . Methods LDS Hospital , located in Salt Lake City , Utah , is a 520-bed private , community , acute-care referral hospital that serves as a teaching facility for the University of Utah Schools of Medicine , Nursing , and Pharmacy . The hospital provides most clinical services but not general pediatric care . An integrated , clinical ly oriented hospital information system has been under development at the institution for more than 20 years [ 36 ] . This system routinely collects and stores all patient data from multiple sources throughout the hospital . The system currently serves as the hospital 's clinical computing system , providing clinical information management and establishing computer-based patient records . The computer-based patient record contains both clinical and financial data . The financial data are derived from a st and ard cost-manager microcomputer software system that is linked to the clinical information system [ 37 , 38 ] . The information system also provides online clinical decision support through its expert system capabilities . Infectious diseases surveillance and therapeutics was the first medical domain to use the expert system features of the hospital information system on a widespread clinical basis [ 39 ] . The clinical decision support systems and the implementation methods for this domain were developed , tested , and implemented by clinical investigators in the Division of Infectious Diseases at LDS Hospital [ 37 - 52 ] . The process used to develop the local consensus guidelines for antimicrobial use was similar to the approach described by East and colleagues [ 34 ] . Our approach also included thorough evaluations of published reports , use of national guidelines and local expert opinion , and exhaustive analyses of the LDS Hospital patient data base ; we subsequently developed step-wise logistic regression models [ 48 , 49 ] . Through various committee representations , we also frequently consulted the medical staff of LDS Hospital ; in these consultations , we presented data and interim results . Using the aforementioned formal techniques [ 34 , 35 ] , the staff also helped develop , test , and implement the clinical practice guidelines that were embedded in the decision support programs . The practice guidelines were encoded into the knowledge base of the hospital information system as rules , algorithms , and predictive models . This allowed for decision support at the point of care , with feedback to physicians in real time . Thus , guideline application was patient specific , and recommendations corresponded to actual clinical conditions at a particular point in time . Feedback to physicians was open looped [ 53 ] , and the physicians ultimately decided whether or not to follow the recommendations . Since 1985 , many of these clinical decision support programs and guidelines have been prospect ively developed and tested in the patient population s of LDS Hospital , often in r and omized studies . Decision support programs have been systematic ally exp and ed to include comprehensive , institution-wide antibiotic management programs . These decision support programs were design ed to comprehensively manage all antibiotic agents used in the institution throughout the continuum of hospital care : 1 ) prophylactic [ surgical ] antibiotic use ; 2 ) empiric antibiotic use [ for suspected infection without microbiological data ] ; and 3 ) therapeutic antibiotic use ( for established infection with microbiological data ) . These programs continually track and assist physicians in managing each patient treated with an antibiotic at LDS Hospital and in all aspects of antibiotic use ; no antibiotic can be prescribed at LDS Hospital without being affected by these decision support programs . The methods used in these programs have been described elsewhere [ 37 - 52 ] . These programs are continually up date d as medical knowledge and the health care delivery system change , both locally and nationally . The surgical prophylactic decision support programs were developed with our surgical colleagues and result ed in strategies that ensured appropriate case selection , delivery time , intra-operative dosing , and duration of antibiotic use rather than solely concentrating on the specific antibiotic agent or class of agents for each surgical procedure [ 41 , 42 , 45 ] . The empiric and therapeutic antibiotic decision support programs provide information to the clinician in the form of computer-generated alerts or suggestions on the following : the presence of resistant pathogens ; untreated infections ; an incorrect dose , route , or interval of an antibiotic ; the absence of current renal function data ; the need for serum drug levels ; population -based probabilities of infections in relation to specific patient variables ; and cost-effective alternatives ( for example , oral therapy or narrower-spectrum agents ) [ 43 , 48 , 49 ] . Furthermore , these management programs monitor patients for excessive or suboptimal antibiotic doses , depending on the patients ' current renal function status [ 46 , 47 ] , and they address the prevention , early detection , and archiving of adverse drug events associated with these agents [ 44 , 46 , 50 ] . All but one of the computer-assisted antibiotic decision support programs described were in clinical use throughout the study period ; the exception was the adverse drug event program , which has been used since 1989 . Beginning in 1985 , investigators in the infectious disease division developed data base analysis programs that quantify antibiotic use and expenditures , identify prescriber and diagnosis-related groups for patients receiving antibiotics , track antibiotic resistance patterns , and distinguish therapeutic from prophylactic use of antibiotics . The reports generated by these data base analysis programs summarize antibiotic use by specific agent and place them in the following categories : numbers of patients treated , total milligrams administered , total doses administered , defined daily doses per 100 occupied bed-days [ 12 , 13 , 54 ] , and total amount spent . We used the number of defined daily doses per 100 occupied bed-days because it is a st and ardized technical unit of measurement that estimates drug use . A defined daily dose is based on the average adult maintenance dose ( usually in grams ) for the primary indication of the drug and is adjusted per 100 occupied bed-days . The concept of the defined daily dose per 100 occupied bed-days was established by a joint project of the Nordic Council on Medicines and the World Health Organization Center for Drug Collaboration Statistics [ 12 , 13 , 54 ] . Because the defined daily dose per 100 occupied bed-days is independent of cost ( which eliminates confounding introduced by the buying practice s of group purchasing organizations ) and differences in dose forms , it establishes a st and ardized basis for comparing drug use . The World Health Organization has agreed that the defined daily dose method of analysis can be THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard BACKGROUND Computerized decision support reduces medication errors in in patients , but limited evidence supports its effectiveness in reducing the coprescribing of interacting medications , especially in the outpatient setting . The usefulness of academic detailing to enhance the effectiveness of medication interaction alerts also is uncertain . METHODS This study used an interrupted time series design . In a health maintenance organization with an electronic medical record , we evaluated the effectiveness of electronic medical record alerts and group academic detailing to reduce the coprescribing of warfarin and interacting medications . Participants were 239 primary care providers at 15 primary care clinics and 9910 patients taking warfarin . All 15 clinics received electronic medical record alerts for the coprescription of warfarin and 5 interacting medications : acetaminophen , nonsteroidal anti-inflammatory medications , fluconazole , metronidazole , and sulfamethoxazole . Seven clinics were r and omly assigned to receive group academic detailing . The primary outcome , the interacting prescription rate ( ie , the number of coprescriptions of warfarin-interacting medications per 10 000 warfarin users per month ) , was analyzed with segmented regression models , controlling for preintervention trends . RESULTS At baseline , nearly a third of patients had an interacting prescription . Coinciding with the alerts , there was an immediate and continued reduction in the warfarin-interacting medication prescription rate ( from 3294.0 to 2804.2 ) , result ing in a 14.9 % relative reduction ( 95 % confidence interval , -19.5 to -10.2 ) at 12 months . Group academic detailing did not enhance alert effectiveness . CONCLUSIONS This study , using a strong and quasi-experimental design in ambulatory care , found that medication interaction alerts modestly reduced the frequency of coprescribing of interacting medications . Additional efforts will be required to further reduce rates of inappropriate prescribing of warfarin with interacting drugs PURPOSE Medication errors contribute significantly to the morbidity and costs of pediatric health care . The authors hypothesized that hospitalwide computerized physician order entry ( CPOE ) in a pediatric hospital would lead to a decrease in medication errors . METHODS The authors retrospectively evaluated and prospect ively analyzed inpatient discharge and usage and adverse drug event ( ADE ) rate data pre- and post introduction of a hospitalwide implementation of CPOE in a tertiary care pediatric hospital . They compared pre- and postintervention ADEs ( Student 's t test ) and computed the number needed to treat ( NNT ) analog . RESULTS Over the 9-month study period , there were 45,615 in patient days and 8619 discharges . Pre-CPOE verbal order regulatory compliance was 80 % , whereas post-CPOE increased to 95 % . Transcription errors were eliminated . All ADEs pre-CPOE were 0.3 + /- 0.04 per 1000 doses , whereas post-CPOE ADEs were 0.37 + /- 0.05 per 1000 doses ( P = .3 ) . Harmful ADEs pre-CPOE were 0.05 + /- 0.017 per 1000 doses , while post-CPOE ADEs were 0.03 + /- 0.003 per 1000 doses ( P = .05 ) . Our NNT data demonstrate that CPOE would prevent 1 ADE every 64 ( 95 % CI 25 - 100 ) patient days . CONCLUSIONS CPOE decreases harmful ADEs in a pediatric hospital , thus leading to increased patient safety . In addition , CPOE provides an automated system for monitoring and improving health care quality In 1998 , the Institute of Medicine 's ( IOM 's ) National Roundtable on Health Care Quality noted that the quality of health care in the United States has substantial problems and that the problems will be addressed only through profound changes to the current health care system ( 1 ) . The recent IOM report ( 2 ) , Crossing the Quality Chasm , contained an unsettling list of studies documenting the prevalence of poor- quality care in the United States . Another IOM report ( 3 ) , To Err Is Human , focused specifically on the current state of patient safety and ways to improve it . All three of these reports recognized the potential for information technology to be an important agent for change . Computer physician order entry ( CPOE ) allows physicians to enter orders directly into a computer rather than h and writing them ( 46 ) . Because CPOE introduces supportive technology into orderingone of the key processes in medicineit has the potential to address many quality problems . Computer physician order entry affords a health care organization opportunities to st and ardize practice ; incorporate clinical decision support into daily practice ; improve interdepartmental communication ; facilitate patient transfers ; and capture data for management , research , and quality monitoring . It provides physicians and other clinicians with an environment that is more appropriate than a paper-based setting to the complexities of today 's medicine . Patients also can have the comfort of knowing that sophisticated technologies are being applied to help ensure their safety . Because implementing CPOE is an expensive and complex project that touches almost all aspects of the health care operation ( 4 ) , only a few health care organizations in the United States have implemented it ( 4 , 7 , 8) . However , such stakeholders as business , government ( 9 ) , and payers ( 10 ) are creating pressures and incentives for organizations to adopt CPOE . In particular , the Leapfrog Group ( 11 ) , a coalition of the country 's largest employers who are eager to acknowledge and reward health-related quality improvement efforts , has identified CPOE as one of three important leaps that organizations can take to substantially improve patient safety . Many health care organizations are moving forward with CPOE efforts . In 2002 , 67 % of respondents to a survey conducted at the Health Information Management and Systems Society ( HIMSS ) Annual Conference said that their organizations were planning to implement CPOE ; 21 % said that they were currently implementing it , and 29 % said that they were actively discussing it ( 12 ) . As health care organizations decide whether and when to tackle the hurdles of implementing CPOE , they should keep in the forefront of their minds the ways in which this technology can be used to improve health care quality and efficiency . We examine the potential benefits , costs , and other important issues associated with CPOE . Benefits of CPOE The National Roundtable on Health Care Quality ( 1 ) recognized that problems in health care quality fall into three categories : the underuse , overuse , and misuse of health care services . The Roundtable noted that reducing the overuse and misuse of health services leads to an increase in health care quality while decreasing costs . Reducing underuse increases quality but may increase costs . Computerized physician order entry may affect all three categories of health care quality problems , as well as inefficiencies in the health care system . Table 1 lists studies that have evaluated the effect of CPOE on various aspects of health care . Table 1 . Studies Showing the Effect of Computer Physician Order Entry on Health Care Variables Several studies have shown that CPOE can reduce underuse . Dexter and colleagues ( 13 ) found that , for eligible patients , reminders in CPOE systems increased ordering rates for prophylactic aspirin for coronary artery disease , pneumococcal vaccine , influenza vaccine , and prophylactic subcutaneous heparin . Teich and colleagues ( 14 ) also found an increase in the use of prophylactic subcutaneous heparin with CPOE . Overhage and colleagues ( 15 ) demonstrated that compliance with the monitoring of drug levels doubled when automated ordering reminders were implemented . The effect of CPOE on care may depend greatly on the subtle details of the application design . In one evaluation , a decision support feature did not increase compliance with guidelines ( 16 ) ; however , success was realized after the design of the feature was enhanced ( 13 ) . Inappropriate admissions accounted for much of the overuse documented by the IOM report ( 2 ) ; CPOE applications may not be able to affect this problem . However , overuse of diagnostic procedures ( 31 , 32 ) and antibiotics ( 33 ) has been well documented and can be addressed by CPOE . As part of the interaction with the user , CPOE can present cost data ( 17 , 18 ) , previous results ( 19 , 20 ) , and information about the likelihood of finding an abnormal result ( 21 , 34 ) , all of which have been shown to reduce the overuse of diagnostic tests . In one trial , the Centers for Disease Control and Prevention 's guidelines for vancomycin use were embedded in a CPOE application ; 28 % ( P < 0.02 ) fewer patients were prescribed vancomycin or had their vancomycin order renewed as compared with CPOE without the automated guidelines ( 26 ) . Of two CPOE-based interventions design ed to reduce the use of radiology examinations , one was successful ( 22 ) , while another had minimal impact ( 23 ) . In summary , more study is needed to underst and which quality problems are best suited to remedy by computerized intervention and which system design s are most successful in achieving behavioral change . Misuse of medications is an important concern that leads to various safety problems , including serious medication errors and preventable adverse drug events , as highlighted in the IOM 's recent report ( 3 ) . Two studies that examined the root cause of serious medication errors ( 35 , 36 ) showed that about half were ordering errors such as an incorrect choice of medication for the patient 's condition , an incorrect dose of the medication given the patient 's physiologic state ( for example , renal insufficiency or advanced age ) , and prescribing a medication to which the patient was known to be allergic . Computer physician order entry systems have the potential to address these problems , and studies have shown that CPOE systems can reduce medication errors ( 24 , 25 ) and associated costs and injuries ( 27 ) . The features of CPOE that promote the safe use of medications include patient-specific dosing suggestions ( 14 , 28 , 37 ) , reminders to monitor drug levels ( 15 ) , reminders to choose an appropriate drug ( 14 , 15 , 26 , 27 ) , checking for drugallergy and drugdrug interactions , st and ardized order sets ( that is , departmentally sanctioned predefined collection s of orders that promote safety and efficiency , especially in complex situations ) , increased legibility , automated communication to ancillary departments , and easy access to patient data and reference information while ordering ( 37 ) . A CPOE application with an integrated antibiotic advisor has been shown to reduce the rates of excessive drug dosages and antibiotic-susceptibility mismatches ( 27 ) . Additional medication-related benefits can be realized if CPOE is well integrated with other components of the medication process . The benefits of interfacing CPOE to a pharmacy application have been described ( 38 ) , and interfacing a CPOE application and an electronic medical administration record at one institution eliminated transcription errors ( 29 ) . Although the IOM report ( 3 ) focused on the misuse of medications in the inpatient setting , new data suggest that the magnitude of the problem is similar in the outpatient setting ( 3941 ) . Emerging technologies that automate prescribing and electronically link the ordering provider , the pharmacy , and the patient may address many medication-related problems in the ambulatory environment . Of note , CPOE applications are complex and are intended for use in complex health care environments . Although CPOE has the potential to reduce many sources of error , organizations must take care as CPOE is implemented so that new kinds of errors will not be introduced ( 25 , 42 ) . Most evaluations of CPOE have examined its effect on specific components of the care process , such as the use of diagnostic testing or medication error rates . A few studies have examined the effect of CPOE on overall hospital costs and length of stay . Evans and colleagues ( 27 ) demonstrated reduced costs ( $ 26 325 vs. $ 35 283 ; P < 0.005 ) and length of stay ( 10.0 days vs. 12.9 days ; P < 0.003 ) in patients in an intensive care unit when the suggestions of a computerized antibiotic advisor incorporated into the ordering process were followed . A r and omized , controlled trial at one hospital ( 30 ) indicated that inpatient costs were 12.7 % lower ( P < 0.02 ) and the length of stay was 0.89 day shorter ( P = 0.11 ) for patients on general medicine wards that used CPOE with decision support . In a time-series design , Mekhjian and colleagues ( 29 ) documented a decreased length of stay at one of two study hospitals from 3.91 days to 3.71 days ( P = 0.02 ) ; the length of stay at the other hospital in the study did not change , and overall costs at the two study hospitals did not change . Research ers are study ing ways that CPOE can help physicians plan a therapeutic regimen ( 43 , 44 ) . Such planning systems hold special promise for improving quality and safety ; however , they involve complex modeling of diagnosis and therapeutics ( 45 ) . To be successful , planning programs must be integrated tightly into the workflow of the application and must not require excessive additional data entry by the physician . To date , attempts at integrating complex clinical guidelines into CPOE have met with limited success ( 46 , 47 ) , largely because published guidelines , although suitable in printed form for use by practicing clinicians , have been difficult to translate BACKGROUND AND METHODS Optimal decisions about the use of antibiotics and other antiinfective agents in critically ill patients require access to a large amount of complex information . We have developed a computerized decision-support program linked to computer-based patient records that can assist physicians in the use of antiinfective agents and improve the quality of care . This program presents epidemiologic information , along with detailed recommendations and warnings . The program recommends antiinfective regimens and courses of therapy for particular patients and provides immediate feedback . We prospect ively studied the use of the computerized antiinfectives-management program for one year in a 12-bed intensive care unit . RESULTS During the intervention period , all 545 patients admitted were cared for with the aid of the antiinfectives-management program . Measures of processes and outcomes were compared with those for the 1136 patients admitted to the same unit during the two years before the intervention period . The use of the program led to significant reductions in orders for drugs to which the patients had reported allergies ( 35 , vs. 146 during the preintervention period ; P<0.01 ) , excess drug dosages ( 87 vs. 405 , P<0.01 ) , and antibiotic-susceptibility mismatches ( 12 vs. 206 , P<0.01 ) . There were also marked reductions in the mean number of days of excessive drug dosage ( 2.7 vs. 5.9 , P<0.002 ) and in adverse events caused by antiinfective agents ( 4 vs. 28 , P<0.02 ) . In analyses of patients who received antiinfective agents , those treated during the intervention period who always received the regimens recommended by the computer program ( n=203 ) had significant reductions , as compared with those who did not always receive the recommended regimens ( n= 195 ) and those in the preintervention cohort ( n = 766 ) , in the cost of antiinfective agents ( adjusted mean , $ 102 vs. $ 427 and $ 340 , respectively ; P<0.001 ) , in total hospital costs ( adjusted mean , $ 26,315 vs. $ 44,865 and $ 35,283 ; P<0.001 ) , and in the length of the hospital stay days ( adjusted mean , 10.0 vs. 16.7 and 12.9 ; P<0.001 ) . CONCLUSIONS ; A computerized antiinfectives-management program can improve the quality of patient care and reduce costs |
526 | 32,495,338 | Based on long-term follow-up , RP compared with WW probably results in substantially improved oncological outcomes in men with localised prostate cancer but also markedly increases rates of urinary incontinence and erectile dysfunction .
Compared to AM , based on follow-up to 10 years , RP probably has similar outcomes with regard to overall and disease-specific survival yet probably reduces the risks of disease progression and metastatic disease .
Urinary function and sexual function are probably decreased for the patients treated with RP | BACKGROUND Prostate cancer is a common cancer but is oftentimes slow growing .
When confined to the prostate , radical prostatectomy ( RP ) , which involves removal of the prostate , offers potential cure that may come at the price of adverse events .
Deferred treatment , involving observation and palliative treatment only ( watchful waiting ( WW ) ) or close monitoring and delayed local treatment with curative intent as needed in the setting of disease progression ( active monitoring (AM)/surveillance ( AS ) ) might be an alternative .
This is an up date of a Cochrane Review previously published in 2010 .
OBJECTIVES To assess effects of RP compared with deferred treatment for clinical ly localised prostate cancer . | BACKGROUND Although there is r and omized evidence that radical prostatectomy improves survival , there are few data on how benefit varies by baseline risk . OBJECTIVE We aim ed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient , using stage , grade , prostate-specific antigen , and age as predictors . DESIGN , SETTING , AND PARTICIPANTS A total of 695 men with T1 or T2 prostate cancer participated in the Sc and inavian Prostate Cancer Group 4 trial ( SPCG-4 ) . INTERVENTION Patients in SPCG-4 were r and omized to radical prostatectomy or conservative management . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Competing risk models were created separately for the radical prostatectomy and the watchful waiting group , with the difference between model predictions constituting the estimated benefit for an individual patient . RESULTS AND LIMITATIONS Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics . At 65 yr of age , the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5 % to 17.2 % for low- versus high-risk patients . Little expected benefit was associated with surgery much beyond age 70 . Only about a quarter of men had an individualized benefit within even 50 % of the mean . A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients . CONCLUSIONS Our model suggests that it is hard to justify surgery in patients with Gleason 6 , T1 disease or in those patients much above 70 yr of age . Conversely , surgery seems unequivocally of benefit for patients who have Gleason 8 , or Gleason 7 , stage T2 . For patients with Gleason 6 T2 and Gleason 7 T1 , treatment is more of a judgment call , depending on patient preference and other clinical findings , such as the number of positive biopsy cores and comorbidities 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 . ) Prostate intervention versus observation trial ( PIVOT ) is the largest and longest r and omized trial conducted in men with early stage prostate cancer detected during the era of wide-spread prostate-specific antigen ( PSA ) testing.1 PIVOT enrolled 731 men and followed them for up to 15 years after r and omization . PIVOT results demonstrate that compared to observation , radical prostatectomy did not result in a significant reduction in all cause or prostate cancer mortality through at least 12 years among men with localized prostate cancer ; absolute differences were less than 3 % . Results changed little after 8 years ; therefore , additional follow-up is unlikely to change our findings . Radical prostatectomy caused related harms within 30 days of surgery in 21 % of men and urinary incontinence and erectile dysfunction through at least 2 years . Prostate cancer mortality was infrequent among all men treated with observation ( approximately 8 % ) and rare ( 3 % ) in men with PSA values of 10 or less or those with low-risk disease , which is important and reassuring findings for men , their families and physicians . Noncancer death rates and surgical quality in PIVOT were similar to other studies enrolling men with early stage prostate cancer . The mean age of 67 years , health status and comorbidities were similar to most men diagnosed with prostate cancer and to other trials . The effect of radical prostatectomy did not vary by patient age , race , health status or presence of other medical conditions . In men with low PSA ( ≤10 ) or low-risk disease death from prostate cancer is rare in men treated with observation and surgery had no reduction in overall or prostate cancer mortality or risk of bone metastases . Surgery may reduce mortality and bone metastases in men with higher PSA or higher-risk disease . However , subgroup findings should be viewed with caution . Any positive results were based on multiple subgroups assessed , rarely met traditional levels of statistical significance , often were sensitive to methods of analysis and may be due to chance . Three-quarters of men with early stage prostate cancer have low PSA or low-risk disease . Men diagnosed today and managed with observation likely have even a better prognosis than men enrolled in PIVOT because of detection of smaller more indolent disease . PIVOT results , combined with other data from r and omized treatment and screening trials , indicate that observation should be the preferred treatment strategy for the majority of men currently diagnosed with early stage prostate cancer . Such a strategy can help men live a similar length of life , avoid death from prostate cancer and prevent treatment related harms and costs . In conclusion , PIVOT demonstrated that surgery did not reduce overall or cancer mortality compared to observation through at least 12 years ' absolute differences were less than 3 % . While surgery may reduce mortality in the minority of men with PSA greater than 10 or with high-risk disease , it did not improve outcomes in men with PSA of 10 or less or with low-risk disease . Observation should be recommended as the preferred treatment option ; it results in similar length of life prevention of prostate cancer death and avoids surgical harms . R and omized controlled trials are needed to evaluate new , more effective and safer screening and treatment approaches for men with aggressive prostate cancer Abstract Context To treat or not to treat is one of the most difficult dilemmas facing prostate cancer patients , especially elderly men with early prostate cancer or small cancer that is contained within the prostate . Objective The primary objective of this review is to analyse the treatment options for patients with localised prostate cancer . This information can be considered alongside other important factors like natural history of disease and diagnostic tests . Evidence acquisition Several r and omised and nonr and omised clinical trials published in the literature investigating the natural history of the disease , diagnostic tests , and treatment options for localised prostate cancer have been review ed for this paper . Evidence synthesis Analysis of prostate-specific antigen ( PSA ) kinetics should play a major role in the management of localised prostate cancer . Trials investigating long-term outcomes of active surveillance are under way . Conclusion Taking all these factors into consideration , the data support active surveillance as an appropriate choice for patients with well-differentiated or moderately differentiated , low-volume prostate cancer who have a life expectancy To present the baseline patient‐reported outcome measures ( PROMs ) in the Prostate Testing for Cancer and Treatment ( ProtecT ) r and omized trial comparing active monitoring , radical prostatectomy and external‐beam conformal radiotherapy for localized prostate cancer and to compare results with other population Importance Prostate cancer screening remains controversial because potential mortality or quality -of-life benefits may be outweighed by harms from overdetection and overtreatment . Objective To evaluate the effect of a single prostate-specific antigen ( PSA ) screening intervention and st and ardized diagnostic pathway on prostate cancer – specific mortality . Design , Setting , and Participants The Cluster R and omized Trial of PSA Testing for Prostate Cancer ( CAP ) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practice s across the United Kingdom . R and omization and recruitment of the practice s occurred between 2001 and 2009 ; patient follow-up ended on March 31 , 2016 . Intervention An invitation to attend a PSA testing clinic and receive a single PSA test vs st and ard ( unscreened ) practice . Main Outcomes and Measures Primary outcome : prostate cancer – specific mortality at a median follow-up of 10 years . Prespecified secondary outcomes : diagnostic cancer stage and Gleason grade ( range , 2 - 10 ; higher scores indicate a poorer prognosis ) of prostate cancers identified , all-cause mortality , and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic . Results Among 415 357 r and omized men ( mean [ SD ] age , 59.0 [ 5.6 ] years ) , 189 386 in the intervention group and 219 439 in the control group were included in the analysis ( n = 408 825 ; 98 % ) . In the intervention group , 75 707 ( 40 % ) attended the PSA testing clinic and 67 313 ( 36 % ) underwent PSA testing . Of 64 436 with a valid PSA test result , 6857 ( 11 % ) had a PSA level between 3 ng/mL and 19.9 ng/mL , of whom 5850 ( 85 % ) had a prostate biopsy . After a median follow-up of 10 years , 549 ( 0.30 per 1000 person-years ) died of prostate cancer in the intervention group vs 647 ( 0.31 per 1000 person-years ) in the control group ( rate difference , −0.013 per 1000 person-years [ 95 % CI , −0.047 to 0.022 ] ; rate ratio [ RR ] , 0.96 [ 95 % CI , 0.85 to 1.08 ] ; P = .50 ) . The number diagnosed with prostate cancer was higher in the intervention group ( n = 8054 ; 4.3 % ) than in the control group ( n = 7853 ; 3.6 % ) ( RR , 1.19 [ 95 % CI , 1.14 to 1.25 ] ; P < .001 ) . More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group ( n = 3263/189 386 [ 1.7 % ] ) than in the control group ( n = 2440/219 439 [ 1.1 % ] ) ( difference per 1000 men , 6.11 [ 95 % CI , 5.38 to 6.84 ] ; P < .001 ) . In the analysis of all-cause mortality , there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group ( RR , 0.99 [ 95 % CI , 0.94 to 1.03 ] ; P = .49 ) . In the instrumental variable analysis for prostate cancer mortality , the adherence-adjusted causal RR was 0.93 ( 95 % CI , 0.67 to 1.29 ; P = .66 ) . Conclusions and Relevance Among practice s r and omized to a single PSA screening intervention vs st and ard practice without screening , there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased . Although longer-term follow-up is under way , the findings do not support single PSA testing for population -based screening . Trial Registration IS RCT N Identifier : IS RCT The Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) concluded that radical prostatectomy ( RP ) offered no survival benefit compared with observation in men with clinical ly localized prostate cancer ( PCa ) . We identified patients within the National Cancer Data base ( NCDB ) for the period 2004 - 2012 who met the inclusion criteria of PIVOT ( ie , histologically confirmed PCa , clinical stage T1 - 2NxM0 , prostate-specific antigen < 50 ng/ml , age < 75 yr , estimated life expectancy > 10 yr , and undergoing RP or observation as initial treatment within 12 mo of diagnosis ) to confirm the generalizability of the PIVOT results to the US population . Life expectancy was calculated using the US Social Security Administration life tables and was adjusted for comorbidities at diagnosis . Compared with PIVOT , men in the NCDB were younger ( mean age 60.3 vs 67.0 yr ) and healthier ( Charlson-Deyo comorbidity index of 0 : 93 % vs 56 % ; both p < 0.001 ) . Furthermore , 42 % of men r and omized to receive RP in PIVOT harbored D'Amico low-risk PCa , whereas 32 % of men undergoing RP in the NCDB had low-risk disease . Our findings were confirmed in a sensitivity analysis including men regardless of life expectancy but satisfying all other inclusion criteria of PIVOT . Given that the NCDB represents nearly 70 % of all incident cancers diagnosed in the United States , our data provide further evidence that PIVOT results may not be generalizable to contemporary clinical practice . PATIENT SUMMARY We observed that men diagnosed with clinical ly localized prostate cancer within the National Cancer Data base ( 2004 - 2012 ) were younger , healthier , and more likely to have radical prostatectomy for higher risk disease than men in the Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) , raising questions about the applicability of PIVOT conclusions to the contemporary US population A fifteen-year follow-up of a prospect i ve , r and omized study comparing placebo with radical prostatectomy as the primary treatment of early prostatic cancer is presented . A total of 111 patients with clinical Stage I or II prostatic cancer , normal acid phosphatase levels , and negative findings on skeletal x-ray film were evaluable . Thirty Stage I patients and 20 Stage II patients received placebo only ; 31 Stage I and 30 Stage II patients underwent radical prostatectomy . The survival status for 95 patients ( 86 % ) was established at the fifteen-year follow-up . No significant differences in crude survival occurred in either stage or in both stages combined . Moreover , the survival curves closely followed reference curves based on expected U.S. mortality for men of comparable ages and races . A statistically significant association between a high Gleason histologic score and poor survival was established . In this study , initial treatment with radical prostatectomy did not yield longer survival than initial placebo treatment alone . However , the findings should be interpreted with caution , since sample size was small and staging procedure was simplified The Sc and inavian Prostate Cancer Group-4 recently reported the long-term survival benefit in men who were r and omized to radical prostatectomy versus men watchful waiting for localized prostate cancer.1 The authors have now presented the companion article that up date s the long-term quality of life evaluation in these men.2 Given the excellent prognosis of patients with early stage prostate cancer , the impact of therapy on patient 's quality of life is a significant factor in the optimal management of this disease . The study was conducted using a disease-specific question naire of important quality of life factors that the authors developed through interviews with men with prostate cancer . The r and omized study groups were also compared to matched contemporary controls . The question naire encompasses the patient 's psychological symptoms , sense of wellbeing , physical symptoms ( erectile dysfunction , weak urinary stream , urinary leakage , nocturia ) , sexual desire and sexuality . The question naire has been vali date d in other studies .3 The study evaluated the quality of life differences between treatment groups after a median follow-up of 12.2 years , which is one of the longest quality of life follow-up assessment s to date in this setting . Radical prostatectomy and watchful waiting had similar incidences for erectile dysfunction ( 84 % and 80 % ) , which were significantly higher than the population control group ( 46 % ) . However , all patients with prostate cancer rated sexuality as less important than the control group . Nonetheless , a greater number of radical prostatectomy patients with erectile dysfunction experience moderate-to-great distress from erectile dysfunction than watchful waiting patients with erectile dysfunction . It is interesting to note that distress from erectile dysfunction in these patients persisted a decade after the radical prostatectomy . Patients in the watchful waiting group had significantly higher rates of weak stream and nocturia than both the radical prostatectomy and control groups . However , patients who received radical prostatectomy had higher rates of urinary incontinence and dependence on protective aids . Anxiety in general was noted to be higher in all patients with prostate cancer . The authors evaluated the change in symptoms in patients who received radical prostatectomy versus watchful waiting and found progression of erectile dysfunction and increased reliance in protective pads in both groups over time . There was also a significant decline in quality of life , increase in erectile dysfunction and increase in urinary symptoms in both the radical prostatectomy and watchful waiting groups . It is difficult to determine whether these long-term changes were due to effects of therapy , ageing or both , as the changes in quality of life and symptoms for the control group were not available for comparison . The results in this article are similar to earlier published results of the same cohort of patients at mean follow-up of 4.1 years , which demonstrated radical prostatectomy to be associated with increased erectile dysfunction and urinary incontinence , and watchful waiting to be associated with increase obstructive urinary symptoms . The self-assessed quality of life was also similar between the two groups.4 Interestingly , patients who died of prostate cancer were excluded from analysis and mortality was not included as a factor in the health-related quality of life measure despite being an important concern to patients . Given that radical prostatectomy is found to improve survival but is associated with decreased quality of life , a better analysis of the tradeoff between quantity and quality of life could be determined using quality -adjusted life years.5 Quality -adjusted life years would provide a more patient-centered measure of outcomes related to radical prostatectomy or watchful waiting by capturing the gains from reduced mortality with the morbidity of therapy . Furthermore , the number of patients who required additional procedures , such as transurethral resection of prostate for urinary obstruction or anti-incontinence procedures , was not determined in this study . These additional procedures needed are also considered important factors in quality of life assessment . A few limitations deserve mention . Notable is the lack of baseline quality of life assessment . This is partially compensated by enrolling an age-matched and region-matched control group of men without prostate cancer . However , 23.8 % of men in the population -based control group were lost to follow-up and did not return the question naire , which raises the potential for bias . The authors did not provide a power calculation for the number of patients needed to detect a difference in quality of life between the three groups . Caution should be exercised in interpreting these findings . The authors note that about 25 % of men in the study were and rogen-deprived , which likely confounds the results for erectile function , libido , mood and sense of wellbeing , for example . It appears that a higher proportion of patients receiving and rogen deprivation therapy were in the watchful waiting group , which creates an imbalance . The effects of and rogen deprivation on quality of life in this cohort of patients has been published previously after a mean follow-up of 4.1 years.6 This study reflects a historical group of patients who had prostate cancer diagnosed because of symptoms , who then received radical prostatectomy versus watchful waiting . Currently , the majority of prostate cancer is diagnosed as result of PSA screening . Moreover , watchful waiting in patients with symptomatic prostate cancer has been predominately replaced by active surveillance in patients with insignificant disease . Therefore , the generalizability of this study to current newly diagnosed prostate cancer patients who elect radical prostatectomy versus watchful waiting is limited In the Sc and inavian Prostate Cancer Group Trial Number 4 ( SPCG-4 ) , 347 men were r and omly assigned to radical prostatectomy and 348 to watchful waiting . In the most recent analysis ( median follow-up time = 12.8 years ) , the cumulative mortality curves had been stable over the follow-up . At 15 years , the absolute risk reduction of dying from prostate cancer was 6.1 % following r and omization to radical prostatectomy , compared with watchful waiting . Hence , 17 need to be r and omized to operation to avert one death . Data on self-reported symptoms , stress from symptoms , and quality of life were collected at 4 and 12.2 years of median follow-up . These question naire studies show an intricate pattern of symptoms evolving after surgery , hormonal treatments , signs of tumor progression , and also from natural aging . This article discusses some of the main findings of the SPCG-4 study BACKGROUND Initial treatment options for low-risk clinical ly localized prostate cancer ( PCa ) include radical prostatectomy ( RP ) or observation . OBJECTIVE To examine cancer-specific mortality ( CSM ) after accounting for other-cause mortality ( OCM ) in PCa patients treated with either RP or observation . DESIGN , SETTING , AND PARTICIPANTS Using the Surveillance Epidemiology and End Results Medicare-linked data base , a total of 44 694 patients ≥65 yr with localized ( T1/2 ) PCa were identified ( 1992 - 2005 ) . INTERVENTION RP and observation . MEASUREMENTS Propensity-score matching was used to adjust for potential selection biases associated with treatment type . The matched cohort was r and omly divided into the development and validation sets . Competing-risks regression models were fitted and a competing-risks nomogram was developed and externally vali date d. RESULTS AND LIMITATIONS Overall , 22,244 ( 49.8 % ) patients were treated with RP versus 22450 ( 50.2 % ) with observation . Propensity score-matched analyses derived 11,669 matched pairs . In the development cohort , the 10-yr CSM rate was 2.8 % ( 2.3 - 3.5 % ) for RP versus 5.8 % ( 5.0 - 6.6 % ) for observation ( absolute risk reduction : 3.0 % ; relative risk reduction : 0.5 % ; p<0.001 ) . In multivariable analyses , the CSM hazard ratio for RP was 0.48 ( 0.38 - 0.59 ) relative to observation ( p<0.001 ) . The competing-risks nomogram discrimination was 73 % and 69 % for prediction of CSM and OCM , respectively , in external validation . The nature of observational data may have introduced a selection bias . CONCLUSIONS On average RP reduces the risk of CSM by half in patients aged ≥65 yr , relative to observation . The individualized protective effect of RP relative to observation may be quantified with our nomogram Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men . In the United States , 90 % of men with prostate cancer are more than age 60 years , diagnosed by early detection with the prostate-specific antigen ( PSA ) blood test , and have disease believed confined to the prostate gl and ( clinical ly localized ) . Common treatments for clinical ly localized prostate cancer include watchful waiting ( WW ) , surgery to remove the prostate gl and ( radical prostatectomy ) , external-beam radiation therapy and interstitial radiation therapy ( brachytherapy ) , and and rogen deprivation . Little is known about the relative effectiveness and harms of treatments because of the paucity of r and omized controlled trials . The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study # 407:Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) , initiated in 1994 , is a multicenter r and omized controlled trial comparing radical prostatectomy with WW in men with clinical ly localized prostate cancer . We describe the study rationale , design , recruitment methods , and baseline characteristics of PIVOT enrollees . We provide comparisons with eligible men declining enrollment and men participating in another recently reported r and omized trial of radical prostatectomy vs WW conducted in Sc and inavia . We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment . From these , 5023 met initial age , comorbidity , and disease eligibility criteria , and a total of 731 men agreed to participate and were r and omized . The mean age of enrollees was 67 years . Nearly one-third were African American . Approximately 85 % reported that they were fully active . The median PSA was 7.8ng/mL ( mean 10.2ng/mL ) . In three-fourths of men , the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise . Using previously developed tumor risk categorizations incorporating PSA levels , Gleason histologic grade , and tumor stage , it was found that approximately 40 % had low-risk , 34 % had medium-risk , and 21 % had high-risk prostate cancer based on local histopathology . Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Sc and inavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Sc and inavian trial . PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States . Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinical ly localized prostate cancer BACKGROUND Radical prostatectomy reduces mortality among men with localized prostate cancer ; however , important questions regarding long-term benefit remain . METHODS Between 1989 and 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012 . The primary end points in the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) were death from any cause , death from prostate cancer , and the risk of metastases . Secondary end points included the initiation of and rogen-deprivation therapy . RESULTS During 23.2 years of follow-up , 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died . Of the deaths , 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer ; the relative risk was 0.56 ( 95 % confidence interval [ CI ] , 0.41 to 0.77 ; P=0.001 ) , and the absolute difference was 11.0 percentage points ( 95 % CI , 4.5 to 17.5 ) . The number needed to treat to prevent one death was 8 . One man died after surgery in the radical-prostatectomy group . And rogen-deprivation therapy was used in fewer patients who underwent prostatectomy ( a difference of 25.0 percentage points ; 95 % CI , 17.7 to 32.3 ) . The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age ( relative risk , 0.45 ) and in those with intermediate-risk prostate cancer ( relative risk , 0.38 ) . However , radical prostatectomy was associated with a reduced risk of metastases among older men ( relative risk , 0.68 ; P=0.04 ) . CONCLUSIONS Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy ; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk . A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment . ( Funded by the Swedish Cancer Society and others . ) BACKGROUND The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen ( PSA ) testing is not known . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer ( mean age , 67 years ; median PSA value , 7.8 ng per milliliter ) to radical prostatectomy or observation and followed them through January 2010 . The primary outcome was all-cause mortality ; the secondary outcome was prostate-cancer mortality . RESULTS During the median follow-up of 10.0 years , 171 of 364 men ( 47.0 % ) assigned to radical prostatectomy died , as compared with 183 of 367 ( 49.9 % ) assigned to observation ( hazard ratio , 0.88 ; 95 % confidence interval [ CI ] , 0.71 to 1.08 ; P=0.22 ; absolute risk reduction , 2.9 percentage points ) . Among men assigned to radical prostatectomy , 21 ( 5.8 % ) died from prostate cancer or treatment , as compared with 31 men ( 8.4 % ) assigned to observation ( hazard ratio , 0.63 ; 95 % CI , 0.36 to 1.09 ; P=0.09 ; absolute risk reduction , 2.6 percentage points ) . The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age , race , coexisting conditions , self-reported performance status , or histologic features of the tumor . Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter ( P=0.04 for interaction ) and possibly among those with intermediate-risk or high-risk tumors ( P=0.07 for interaction ) . Adverse events within 30 days after surgery occurred in 21.4 % of men , including one death . CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA testing , radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality , as compared with observation , through at least 12 years of follow-up . Absolute differences were less than 3 percentage points . ( Funded by the Department of Veterans Affairs Cooperative Studies Program and others ; PIVOT Clinical Trials.gov number , NCT00007644 . ) Abstract Objective . This study aim ed to develop a probabilistic decision support model to calculate the lifetime incremental cost-effectiveness ratio ( ICER ) between radical prostatectomy and watchful waiting for different patient groups . Material and methods . A r and omized trial ( SPCG-4 ) provided most data for this study . Data on survival , costs and quality of life were inputs in a decision analysis , and a decision support model was developed . The model can generate cost-effectiveness information on subgroups of patients with different characteristics . Results . Age was the most important independent factor explaining cost-effectiveness . The cost-effectiveness value varied from 21 026 Swedish kronor ( SEK ) to 858 703 SEK for those aged 65 to 75 years , depending on Gleason scores and prostate-specific antigen ( PSA ) values . Information from the decision support model can support decision makers in judging whether or not radical prostatectomy ( RP ) should be used to treat a specific patient group . Conclusions . The cost-effectiveness ratio for RP varies with age , Gleason scores , and PSA values . Assuming a threshold value of 200 000 SEK per quality -adjusted life-year ( QALY ) gained , for patients aged ≤70 years the treatment was always cost-effective , except at age 70 , Gleason 0–4 and PSA ≤10 . Using the same threshold value at age 75 , Gleason 7–9 ( regardless of PSA ) and Gleason 5–6 ( with PSA > 20 ) were cost-effective . Hence , RP was not perceived to be cost-effective in men aged 75 years with low Gleason and low PSA . Higher threshold values for patients with clinical ly localized prostate cancer could be discussed For patients with low‐risk prostate cancer ( PCa ) , active surveillance ( AS ) may produce oncologic outcomes comparable to those achieved with radical prostatectomy ( RP ) . Health‐related quality ‐of‐life ( HRQoL ) outcomes are important to consider , yet few studies have examined HRQoL among patients with PCa who were managed with AS . In this study , the authors compared longitudinal HRQoL in a prospect i ve , racially diverse , and contemporary cohort of patients who underwent RP or AS for low‐risk PCa Management of localized prostate cancer is controversial due in part to the lack of r and omized controlled trial information in men diagnosed with prostate specific antigen ( PSA ) testing . Men with low risk or low PSA ( < 10 ng/ml ) prostate cancer comprise up to 70 % of men currently diagnosed . Evidence suggests an excellent long-term prognosis with observation though nearly 90 % are treated with surgery ( radical prostatectomy ) , external beam radiation , or brachytherapy . Results from the Prostate cancer Intervention Versus Observation Trial ( PIVOT ) provide high quality Level 1 evidence that observation compared to surgery results in similar long-term overall and prostate cancer survival , prevention of bone metastases and avoidance of surgery related harms . Combined with emerging evidence from screening , natural history , decision analysis and cost-effectiveness modeling studies , these data demonstrate that observation is the preferred treatment option for men with low risk and possibly low PSA prostate cancer . Recommending against PSA testing or , in men who still desire testing , raising thresholds of PSA values used to define abnormal , lengthening intervals between PSA tests and discontinuing testing in men with a life expectancy less than 15 years will reduce diagnostic and treatment related harms without adversely impacting overall or disease specific mortality and morbidity OBJECTIVES To up date counselling of patients in an experienced center , we assessed intraoperative and perioperative complications in a consecutive series of contemporary radical retropubic prostatectomy for localized prostate cancer . METHODS In a prospect i ve study , we analyzed all intraoperative and perioperative complications within 30 days in a consecutive series of 1243 patients undergoing radical prostatectomy between January 1999 and February 2002 . All adverse events were graduated in major and minor complications by their severity and sequel . RESULTS There were no deaths . Overall , 996 patients ( 80.2 % ) were not affected by any complication . Major complications were observed in 50 patients ( 4.0 % ) , minor complications in 197 ( 15.8 % ) . Pelvic lymphadenectomy was performed in 861 ( 69.3 % ) patients . This procedure was associated with a significantly higher rate of lymphoceles requiring a drainage , 4.2 % versus 0.3 % ( p<0.006 ) and a higher rate of deep venous thrombosis , 1.4 % versus 0.5 % ( p<0.2 ) , respectively . CONCLUSION Radical retropubic prostatectomy is a safe surgical procedure . Postoperatively the majority of our patients was not compromised by any complication within 30 days . Furthermore , due to a higher rate of lymphoceles and thromboembolic events the indication for pelvic lymphadenectomy should be considered carefully BACKGROUND Radical prostatectomy is widely used in the treatment of early prostate cancer . The possible survival benefit of this treatment , however , is unclear . We conducted a r and omized trial to address this question . METHODS From October 1989 through February 1999 , 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b , T1c , or T2 were r and omly assigned to watchful waiting or radical prostatectomy . We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death . The primary end point was death due to prostate cancer , and the secondary end points were overall mortality , metastasis-free survival , and local progression . RESULTS During a median of 6.2 years of follow-up , 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died ( P=0.31 ) . Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting ( 8.9 percent ) and in 16 of 347 of those assigned to radical prostatectomy ( 4.6 percent ) ( relative hazard , 0.50 ; 95 percent confidence interval , 0.27 to 0.91 ; P=0.02 ) . Death due to other causes occurred in 31 of 348 men in the watchful-waiting group ( 8.9 percent ) and in 37 of 347 men in the radical-prostatectomy group ( 10.6 percent ) . The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting ( relative hazard , 0.63 ; 95 percent confidence interval , 0.41 to 0.96 ) . CONCLUSIONS In this r and omized trial , radical prostatectomy significantly reduced disease-specific mortality , but there was no significant difference between surgery and watchful waiting in terms of overall survival Background : Statins are associated with lower PSA levels . As PSA is the primary method for prostate cancer ( PC ) screening , this confounds any associations between statins and risk of being diagnosed with PC . Thus , we examined the association between statins and cancer and high- grade cancer in REDUCE , where biopsies were largely PSA-independent . Methods : Post-hoc secondary analysis of REDUCE , which was a prospect i ve multinational r and omized controlled trial of dutasteride vs placebo for 4 years among men aged 50–75 years with PSA of 2.5–10.0 ng ml−1 and a negative biopsy at baseline , and included PSA-independent biopsies m and ated at 2- and 4-years . Analyses were limited to men who underwent at least one biopsy while under study ( n=6729 ) . The association between baseline statin use and risk of overall , high- grade ( Gleason ⩾7 ) or low- grade ( Gleason ⩽6 ) PC vs no cancer was examined using multinomial logistic regression adjusting for age , race , baseline PSA , prostate volume , rectal examination findings , body mass index ( BMI ) , comorbidities , smoking , alcohol intake and treatment arm . Results : Of 6729 men who had at least one biopsy while on study , 1174 ( 17.5 % ) were taking a statin at baseline . Men taking statins were older , had lower PSA levels , higher BMI values and lower serum testosterone and dihydrotestosterone levels , though differences , were slight . Statin use was not associated with overall PC diagnosis ( multivariable OR 1.05 , 95 % CI 0.89–1.24 , P=0.54 ) . When stratified by grade , statin use was not associated with low- grade ( multivariable OR 1.03 , 95 % CI 0.85–1.25 , P=0.75 ) or high- grade cancer ( multivariable OR 1.11 , 95 % CI 0.85–1.45 , P=0.46 ) . The major limitation is the inclusion of only men with a negative baseline biopsy . Conclusions : Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA , statins were not associated with cancer or high- grade cancer To learn about the natural history of untreated early stage prostatic cancer ( stage T0 - 2NXM0 ) progression-free , disease specific , overall survival and the need for palliative care were evaluated in a population -based and regionally well defined cohort from Sweden . Complete followup , with a mean observation of 12.5 years , was achieved in 223 consecutively diagnosed , eligible patients ( 98 % ) of all ages . Patients with progression were hormonally treated ( orchiectomy or estrogens ) if they had symptoms . After a mean of 12.5 years only 23 patients ( 10 % ) had died of prostate cancer and 125 of 148 deaths ( 84 % ) were of other causes . The 10-year disease specific survival rate was 85 % ( 95 % confidence interval 79 to 91 % ) and was equally high ( 89 % ) in a subgroup of 58 patients who met current indications for radical prostatectomy . The progression-free 10-year survival rate was 55 % ( 95 % confidence interval 46 to 63 % ) but in 49 of 77 patients local growth provided the only evidence of progression and endocrine treatment was generally successful in these cases . Following an initial increase , the rate of disease progression and death from prostate cancer decreased during the last years of followup . The low disease specific mortality rate , especially in patients with highly and moderately differentiated tumors , means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison . One such trial is in progress in Sweden and Finl and evaluating deferred treatment and radical prostatectomy . As of the beginning of December 1993 , 330 patients were included in the study No data from prospect i ve r and omized studies comparing radical prostatectomy , radiotherapy and deferred treatment for localized prostatic cancer are currently available . Comparison of retrospective series , however , strongly suggests a clear superiority of radical prostatectomy over other attempts to cure prostate cancer , and especially over the ' watchful waiting ' strategy . This concerns survival data as well as quality of life and psychological aspects . In 1994 , the Department of Veterans Affairs and The National Cancer Institute in the United States initiated a r and omized controlled study comparing radical prostatectomy vs expectant management for the treatment of localized prostate cancer , the ' Prostate Cancer Intervention vs Observation Trial ( PIVOT ) ' . Until the results of this study become available , the decision on how to manage a patient with a newly-diagnosed clinical ly localized prostate cancer has to be based on current knowledge . The current knowledge is that localized prostate cancer can be cured by radical prostatectomy with acceptable treatment-related morbidity . Therefore , the chance of receiving curative treatment should be offered to every man with localized prostate cancer and a life expectancy of 10 or more years The Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) is a r and omized controlled trial sponsored by the Department of Veterans Affairs and the National Cancer Institute . PIVOT will enroll 2,000 participants from at least 80 Veterans Administration and National Cancer Institute medical centers . The purpose of PIVOT is to determine which of 2 strategies is superior for managing clinical ly localized prostate cancer ( stage T1/T2NXM0 ) of all histological grade s. Patients less than 75 years old will be r and omized to either radical prostatectomy with early intervention for disease persistence/recurrence or expectant management with palliative therapy reserved for symptomatic or metastatic disease progression . Participants will be excluded if they have received prior therapy for prostate cancer ( except transurethral resection of the prostate ) or are judged not to be c and i date s for radical prostectomy . All patients with newly diagnosed prostate cancer will be recorded on the PIVOT screening log . Registry information will include patient age , race , prostate specific antigen level , clinical stage , histological tumor grade , initial therapy , and vital status . Patients meeting eligibility criteria will watch an information and r and omization video tape developed for PIVOT . Participants will be r and omized over a 3-year period and followed for a minimum of 12 years . Data collected at followup will include urological symptoms , disease and treatment related morbidity , and disease specific and overall quality of life . Evidence of symptomatic or asymptomatic disease persistence , recurrence or progression will be measured by question naire , physical examination , digital rectal examination , prostate specific antigen and annual bone scan . The primary study end point will be all cause mortality . Secondary outcomes will include prostate cancer and treatment specific morbidity and mortality rates , health status , predictors of disease specific outcomes and cost-effectiveness . PIVOT will provide a 90 % power to detect a 15 % relative decrease in all cause mortality and a 35 % relative decrease in prostate cancer specific mortality rate by either treatment strategy Background The Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) r and omized 731 men with localized prostate cancer to radical prostatectomy or observation . Purpose We describe the methods and results for cause-of-death assignments in PIVOT , and compare them to alternative strategies for ascertaining prostate cancer – specific mortality , as well as to the methods and results in the similar Sc and inavian Prostate Cancer Group Study 4 ( SPCG-4 ) trial . Methods Three PIVOT Endpoints Committee members , blinded to r and omized treatment assignments , review ed medical records and death certificates when available to assign a cause of death using a primary and a secondary adjudication question . Initial disagreements were resolved through discussion . The level of initial agreement among committee members was examined , as well as guesses at r and omized treatment assignments for a convenience sample of cases . Final cause of death determinations were compared to death certificates . Results Complete agreement on cause of death by all three committee members before any discussion was achieved in 200/354 ( 56 % ) cases on the primary and 209/354 ( 59 % ) cases on the secondary . However , complete agreement on the primary rose to 306/354 ( 86 % ) when ‘ definite ’ and ‘ probably ’ categories were collapsed , as planned a priori . The three committee members ’ proportions of correct guesses of r and omized treatment assignment were 82/121 ( 68 % ) , 113/148 ( 76 % ) , and 99/134 ( 74 % ) . Using the committee ’s final adjudications as a gold st and ard , death certificates had suboptimal sensitivities , specificities , or predictive values depending on how they were used to determine cause of death . Limitations There was no separate ‘ gold st and ard ’ by which to judge the accuracy of the final endpoints committee adjudications , and useful death certificates could not be obtained on about a third of PIVOT participants who died . Conclusions The low level of initial agreement on cause of death among endpoint committee members and the potential for biased determinations due to partial unblinding to treatment assignment raise method ologic concerns about using prostate cancer mortality as an endpoint in clinical trials like PIVOT Background : The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) and the US Prostate , Lung , Colorectal , and Ovarian ( PLCO ) cancer screening trial . Objective : To examine limitations of basing screening policy on evidence from screening trials . Methods : We review ed published modeling studies that examined population and trial data . The studies ( 1 ) project the roles of screening and changes in primary treatment in the US mortality decline ; ( 2 ) extrapolate the ERSPC mortality reduction to the long-term US setting ; ( 3 ) estimate overdiagnosis based on US incidence trends ; and ( 4 ) quantify the impact of control arm screening on PLCO mortality results . Results : Screening plausibly explains 45 % and changes in primary treatment can explain 33 % of the US prostate cancer mortality decline . Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial . Approximately 28 % of screen-detected cases are overdiagnosed in the United States versus 58 % of screen-detected cases suggested by the ERSPC results . Control arm screening can explain the null result in the PLCO trial . Conclusions : Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening— and more favorable harm-benefit tradeoffs — than has been suggested by empirical trial evidence Objectives The Swedish Family-Cancer Data base has been the major source of population -based prospect i ve data on familial risks on most cancers , including prostate cancer . In the present review , I focus on three lines of family studies with novel results . Methods The covered studies originate from the same data base with publication date s spanning a period of somewhat over 3 years . Age-specific hazard ratios ( HRs ) of incident prostate cancer and fatal prostate cancer were determined according to the number of affected relatives . Cumulative risks for incidence and death were calculated for the various types of families . Finally , data on the familial association of prostate cancer with some other cancers were review ed . Results If the father had prostate cancer , the HR for sons was 2.1 and it increased to 17.7 when three brothers were affected . The highest HR ( 23 ) was observed for men before age 60 years with three affected brothers . The patterns for fatal familial prostate cancer were similar . Other review ed sets of data showed evidence for the familial concordance of good and poor survival in prostate cancer . Familial risks were somewhat higher for fatal than for incident prostate cancer , suggesting that fatal prostate cancers may be a genetic subgroup . Conclusions Considering the high familial risks in fatal prostate cancer , family history remains an important prognostic piece of information useful for clinical genetic counseling . Obviously , preventive measures for at-risk men are needed but these are beyond the present paper . Starting screening before any prostate cancers are diagnosed in a family appears counterproductive BACKGROUND Using observational data to assess the relative effectiveness of alternative cancer treatments is limited by patient selection into treatment , which often biases interpretation of outcomes . We evaluated methods for addressing confounding in treatment and survival of patients with early-stage prostate cancer in observational data and compared findings with those from a benchmark r and omized clinical trial . METHODS We selected 14 302 early-stage prostate cancer patients who were aged 66 - 74 years and had been treated with radical prostatectomy or conservative management from linked Surveillance , Epidemiology , and End Results -Medicare data from January 1 , 1995 , through December 31 , 2003 . Eligibility criteria were similar to those from a clinical trial used to benchmark our analyses . Survival was measured through December 31 , 2007 , by use of Cox proportional hazards models . We compared results from the benchmark trial with results from models with observational data by use of traditional multivariable survival analysis , propensity score adjustment , and instrumental variable analysis . RESULTS Prostate cancer patients receiving conservative management were more likely to be older , nonwhite , and single and to have more advanced disease than patients receiving radical prostatectomy . In a multivariable survival analysis , conservative management was associated with greater risk of prostate cancer-specific mortality ( hazard ratio [ HR ] = 1.59 , 95 % confidence interval [ CI ] = 1.27 to 2.00 ) and all-cause mortality ( HR = 1.47 , 95 % CI = 1.35 to 1.59 ) than radical prostatectomy . Propensity score adjustments result ed in similar patient characteristics across treatment groups , although survival results were similar to traditional multivariable survival analyses . Results for the same comparison from the instrumental variable approach , which theoretically equalizes both observed and unobserved patient characteristics across treatment groups , differed from the traditional multivariable and propensity score results but were consistent with findings from the subset of elderly patient with early-stage disease in the trial ( ie , conservative management vs radical prostatectomy : for prostate cancer-specific mortality , HR = 0.73 , 95 % CI = 0.08 to 6.73 ; for all-cause mortality , HR = 1.09 , 95 % CI = 0.46 to 2.59 ) . CONCLUSION Instrumental variable analysis may be a useful technique in comparative effectiveness studies of cancer treatments if an acceptable instrument can be identified 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 BACKGROUND Quality -of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer . OBJECTIVE To evaluate how follow-up time , number of physical symptoms , and presence of and rogen deprivation affected quality of life among men r and omized to radical prostatectomy or watchful waiting . DESIGN , SETTING , AND PARTICIPANTS The study group was composed of all 376 living men included in the Swedish part of the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) between January 1 , 1989 , and February 29 , 1996 . Quality -of-life data were collected after a mean follow-up time of 4.1 yr . INTERVENTION All patients were r and omly assigned to radical prostatectomy or watchful waiting . Forty-five men were and rogen deprived . MEASUREMENTS Data of specific symptoms , symptom-induced stress , sense of well-being , and self-assessed quality of life were obtained by means of a question naire . Psychological symptoms were assessed using seven-point visual digital scales . RESULTS AND LIMITATIONS In analyses stratified on the basis of the numbers of physical symptoms , anxiety and depressed mood were less common , and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group . As the number of physical symptoms increased , all psychological variables became worse and more prominent in the watchful waiting group . After a follow-up time of 6 - 8 yr , a significant decrease in quality of life ( p=0.03 ) was seen in the watchful waiting group . Twenty-four percent of and rogen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60 % in the radical prostatectomy group . Eighty-eight percent of patients had clinical ly detected tumors . CONCLUSIONS And rogen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting . The number of physical symptoms was associated with the level of quality of life . Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group ( p=0.03 ) BACKGROUND There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer ( PCa ) . OBJECTIVE To evaluate relative survival in men with potentially curable PCa in relation to Gleason score ( GS ) and treatment as practice d in the community at large . DESIGN , SETTING , AND PARTICIPANTS A population -based study including all men with localised PCa registered in Sweden 's National Prostate Cancer Register . INTERVENTIONS Hormonal therapy , watchful waiting , and treatment with curative intent . MEASUREMENTS The ratio of observed deaths to expected deaths , determined from survival in the general male population of the same age , was assessed using Poisson regression analysis , with GS and treatment as covariates . Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis . RESULTS AND LIMITATIONS A total of 31,903 men with potentially curable tumour ( T1-T3 , N0/NX , M0/MX , age < 75 yr , and prostate-specific antigen [ PSA ] < 20 ng/ml ) were identified . GS was recorded for 28,454 of these men . Some 19,606 men ( 60.8 % ) were treated with curative intent , and 12,645 men ( 39.2 % ) were given either hormonal treatment or expectant management . The ratios between observed and expected survival gradually increased for men with GS 10 , with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent . There was a significant interaction between GS and treatment , with a relatively greater benefit from treatment with curative intent for men with high- grade tumours . The results have to be interpreted with some caution , as there was no r and omisation between the treatment groups . CONCLUSIONS Survival for men with well-differentiated tumours is close to that of the general population , regardless of treatment , but the outcome is dismal for men with poorly differentiated tumours , whichever treatment is applied . Nevertheless , men with poorly differentiated tumours benefit more from curative treatment than do men with well- differentiated tumours BACKGROUND Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options . We report the study design , participant sociodemographic and clinical characteristics , and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment ( ProtecT ) trial , which aims to investigate the effectiveness of treatments for localised prostate cancer . METHODS In this r and omised phase 3 trial , men aged 50 - 69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen ( PSA ) test . Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher . Consenting participants with clinical ly localised prostate cancer were r and omly assigned to active monitoring ( surveillance strategy ) , radical prostatectomy , or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system . R and omisation was stratified by site ( minimised for differences in participant age , PSA results , and Gleason score ) . The primary endpoint is prostate cancer mortality at a median 10-year follow-up , ascertained by an independent committee , which will be analysed by intention to treat in 2016 . This trial is registered with Clinical Trials.gov , number NCT02044172 , and as an International St and ard R and omised Controlled Trial , number IS RCT N20141297 . FINDINGS Between Oct 1 , 2001 , and Jan 20 , 2009 , 228,966 men were invited to attend an appointment with a specialist nurse . Of the invited men , 100,444 ( 44 % ) attended their initial appointment and 82,429 ( 82 % ) of attenders had a PSA test . PSA concentration was below the biopsy threshold in 73,538 ( 89 % ) men . Of the 8566 men with a PSA concentration of 3·0 - 19·9 μg/L , 7414 ( 87 % ) underwent biopsies . 2896 men were diagnosed with prostate cancer ( 4 % of tested men and 39 % of those who had a biopsy ) , of whom 2417 ( 83 % ) had clinical ly localised disease ( mostly T1c , Gleason score 6 ) . With the addition of 247 pilot study participants recruited between 1999 and 2001 , 2664 men were eligible for the treatment trial and 1643 ( 62 % ) agreed to be r and omly assigned ( 545 to active monitoring , 545 to radiotherapy , and 553 to radical prostatectomy ) . Clinical and sociodemographic characteristics of r and omly assigned participants were balanced across treatment groups . INTERPRETATION The ProtecT trial r and omly assigned 1643 men with localised prostate cancer to active monitoring , radiotherapy , or surgery . Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials . FUNDING UK National Institute for Health Research Health Technology Assessment Programme Purpose To collect data on primary treatment decision and follow-up in patients with diagnosed , histologically confirmed localized ( T1a – T2c/N0/M0 ) prostate cancer ( PCa ) for up to 5 years in a prospect i ve observational non-interventional study . Methods Patients were non-r and omly allocated to one of the five treatment strategies : hormone therapy , active surveillance , radiation , operation , or watchful waiting . Results A total of 3169 patients were included by 259 participating sites ; 2957 patients had at least one follow-up visit . 54.8 % of tumors at baseline were staged as T1c , 38 % as T2a – T2c , and 7.1 % as T1a or T1b ( missing : 0.2 % ) . 38.9 , 32.6 and 26.6 % of patients were classified as low risk , intermediate risk , and high risk according to d’Amico , respectively ( missing : 1.8 % ) . 56.6 % of patients underwent prostatectomy as primary therapy , 16.4 % received radiation , 6.9 % HT , 15.8 and 4.3 % decided for AS or WW . Mean follow-up was 28.4 months . Progression rates were between 8.6 % ( RT ) and 33.1 % ( AS ) . Conclusion Whereas RP remains the main treatment option of localized PCa , active surveillance appears to become an accepted and selectively employed treatment option . Careful selection of patients is documented by the highest proportion of patients with low risk ( 82.5 % ) , PSA density < 0.2 ng/ml/ml ( 77.5 % ) , T1 staging ( 83.6 % ) , Gleason score ≤6 ( 92.5 % ) , ≤2 positive biopsies ( 79.4 % ) , and lowest mean PSA ( 5.8 ng/ml ) in the AS group . The relatively high progression rate in the AS group has to be considered in the context of treatment changes ; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of > 3 months BACKGROUND For men with localised prostate cancer , surgery provides a survival benefit compared with watchful waiting . Treatments are associated with morbidity . Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from r and omised setting s. We report results for quality of life for men in the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) after a median follow-up of more than 12 years . METHODS All living Swedish and Finnish men ( 400 of 695 ) r and omly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis . An additional 281 men were included in a population -based control group matched for region and age . Physical symptoms , symptom-induced stress , and self-assessed quality of life were evaluated with a study -specific question naire . Longitudinal data were available for 166 Swedish men who had answered quality -of-life question naires at an earlier timepoint . FINDINGS 182 ( 88 % ) of 208 men in the radical prostatectomy group , 167 ( 87 % ) of 192 men in the watchful-waiting group , and 214 ( 76 % ) of 281 men in the population -based control group answered the question naire . Men in SPCG-4 had a median follow-up of 12·2 years ( range 7 - 17 ) and a median age of 77·0 years ( range 61 - 88 ) . High self-assessed quality of life was reported by 62 ( 35 % ) of 179 men allocated radical prostatectomy , 55 ( 34 % ) of 160 men assigned to watchful waiting , and 93 ( 45 % ) of 208 men in the control group . Anxiety was higher in the SPCG-4 groups ( 77 [ 43 % ] of 178 and 69 [ 43 % ] of 161 men ) than in the control group ( 68 [ 33 % ] of 208 men ; relative risk 1·42 , 95 % CI 1·07 - 1·88 ) . Prevalence of erectile dysfunction was 84 % ( 146 of 173 men ) in the radical prostatectomy group , 80 % ( 122 of 153 ) in the watchful-waiting group , and 46 % ( 95 of 208 ) in the control group and prevalence of urinary leakage was 41 % ( 71 of 173 ) , 11 % ( 18 of 164 ) , and 3 % ( six of 209 ) , respectively . Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting . In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart , 38 ( 45 % ) of 85 men allocated radical prostatectomy and 48 ( 60 % ) of 80 men allocated watchful waiting reported an increase in number of physical symptoms ; 50 ( 61 % ) of 82 and 47 ( 64 % ) of 74 men , respectively , reported a reduction in quality of life . INTERPRETATION For men in SPCG-4 , negative side-effects were common and added more stress than was reported in the control population . In the radical prostatectomy group , erectile dysfunction and urinary leakage were often consequences of surgery . In the watchful-waiting group , side-effects can be caused by tumour progression . The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions . An underst and ing of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information . FUNDING US National Institutes of Health ; Swedish Cancer Society ; Foundation in Memory of Johanna Hagstr and and Sigfrid Linnér In a study by the Veterans Administration Cooperative Urological Research Group ( VACURG ) , 142 patients with localized prostate cancer , VACURG stage I and II , were r and omized between radical prostatectomy plus placebo versus placebo alone as initial treatment . 111 patients were evaluable for treatment comparison . Median follow-up for survival is 23 years . The prognostic value of Gleason histologic grading was confirmed . A difference in overall survival in favor of radical prostatectomy was observed in stage I patients . However , after adjustment for imbalance in age distribution , no statistically significant differences in survival could be demonstrated in either stage or in both stages combined . The results are discussed considering the small sample size and the limited statistical power of the study Abstract Objective . The cost of radical prostatectomy ( RP ) compared to watchful waiting ( WW ) has never been estimated in a r and omized trial . The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care . Material and methods . This investigation used the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) trial , comparing RP to WW , and included data from 212 participants living in two counties in Sweden from 1989 to 1999 ( 105 r and omized to WW and 107 to RP ) . All costs were included from r and omization date until death or end of follow-up in July 2007 . Re source use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient . Results . During a median follow-up of 12 years , the overall cost in the RP group was 34 % higher ( p < 0.01 ) than in the WW group , corresponding to € 6123 in Sweden . The difference was driven almost exclusively by the cost of the surgical procedure . The cost difference between RP and WW was two times higher among men with low ( 2–6 ) than among those with high ( 7–10 ) Gleason score . Conclusion . In this economic evaluation of RP versus WW of localized prostate cancer in a r and omized study , RP was associated with 34 % higher costs . This difference , attributed exclusively to the cost of the RP procedure , was not overcome during extended follow-up The natural history of early prostatic cancer has been evaluated in 223 patients with localized ( T0 - 2 , NX , M0 ) , newly diagnosed , untreated prostatic cancer in a population -based study . No initial treatment was given and after an observation time of 66 - 150 months , 73 patients ( 33 % ) have progressed ( 25 with metastases ) and 109 died but only 17 of prostatic cancer . Cumulative progression-free survival after 5 and 10 years was 73.1 % and 64.3 % respectively . Observed survival after 5 and 10 years was 67.3 % and 44.1 % respectively and the corresponding corrected survival 93.8 % and 88.7 % . Fifty-eight of the 223 patients filled the present criteria for radical prostatectomy . With only hormonal manipulation after symptomatic progression the corrected survival was very high , 98.0 % after 5 years and 89.1 % after 10 years among these 58 patients . As a result of this study a r and omized trial comparing deferred treatment with radical prostatectomy in this group of patients has been started in Finl and and Sweden BACKGROUND The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one r and omized trial . In 2005 , we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up . We now report results after 3 more years of follow-up . METHODS From October 1 , 1989 , through February 28 , 1999 , 695 men with clinical ly localized prostate cancer were r and omly assigned to radical prostatectomy ( n = 347 ) or watchful waiting ( n = 348 ) . Follow-up was complete through December 31 , 2006 , with histopathologic review and blinded evaluation of causes of death . Relative risks ( RRs ) were estimated using the Cox proportional hazards model . Statistical tests were two-sided . RESULTS During a median of 10.8 years of follow-up ( range = 3 weeks to 17.2 years ) , 137 men in the surgery group and 156 in the watchful waiting group died ( P = .09 ) . For 47 of the 347 men ( 13.5 % ) who were r and omly assigned to surgery and 68 of the 348 men ( 19.5 % ) who were not , death was due to prostate cancer . The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up . At 12 years , 12.5 % of the surgery group and 17.9 % of the watchful waiting group had died of prostate cancer ( difference = 5.4 % , 95 % confidence interval [ CI ] = 0.2 to 11.1 % ) , for a relative risk of 0.65 ( 95 % CI = 0.45 to 0.94 ; P = .03 ) . The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up . At 12 years , 19.3 % of men in the surgery group and 26 % of men in the watchful waiting group had been diagnosed with distant metastases ( difference = 6.7 % , 95 % CI = 0.2 to 13.2 % ) , for a relative risk of 0.65 ( 95 % CI = 0.47 to 0.88 ; P = .006 ) . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it ( RR = 14.2 , 95 % CI = 3.3 to 61.8 ; P < .001 ) . CONCLUSION Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery BACKGROUND Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men . Ninety percent of men with prostate cancer are over aged 60 years , diagnosed by early detection with the prostate specific antigen ( PSA ) blood test and have disease believed confined to the prostate gl and ( clinical ly localized ) . Common treatments for clinical ly localized prostate cancer include watchful waiting surgery to remove the prostate gl and ( radical prostatectomy ) , external beam radiation therapy and interstitial radiation therapy ( brachytherapy ) and and rogen deprivation . Little is known about the relative effectiveness and harms of treatments due to the paucity of r and omized controlled trials . The VA/NCI/AHRQ Cooperative Studies Program Study # 407 : Prostate cancer Intervention Versus Observation Trial ( PIVOT ) , initiated in 1994 , is a multicenter r and omized controlled trial comparing radical prostatectomy to watchful waiting in men with clinical ly localized prostate cancer . METHODS We describe the study rationale , design , recruitment methods and baseline characteristics of PIVOT enrollees . We provide comparisons with eligible men declining enrollment and men participating in another recently reported r and omized trial of radical prostatectomy versus watchful waiting conducted in Sc and inavia . RESULTS We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment . From these , 5023 met initial age , comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were r and omized . The mean age of enrollees was 67 years . Nearly one-third were African-American . Approximately 85 % reported they were fully active . The median prostate specific antigen ( PSA ) was 7.8 ng/mL ( mean 10.2 ng/mL ) . In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise . Using previously developed tumor risk categorizations incorporating PSA levels , Gleason histologic grade and tumor stage , approximately 43 % had low risk , 36 % had medium risk and 20 % had high-risk prostate cancer . Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Sc and inavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Sc and inavian trial . CONCLUSIONS PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States . Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinical ly localized prostate cancer BACKGROUND In 2002 , we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer . After three more years of follow-up , we report estimated 10-year results . METHODS From October 1989 through February 1999 , 695 men with early prostate cancer ( mean age , 64.7 years ) were r and omly assigned to radical prostatectomy ( 347 men ) or watchful waiting ( 348 men ) . The follow-up was complete through 2003 , with blinded evaluation of the causes of death . The primary end point was death due to prostate cancer ; the secondary end points were death from any cause , metastasis , and local progression . RESULTS During a median of 8.2 years of follow-up , 83 men in the surgery group and 106 men in the watchful-waiting group died ( P=0.04 ) . In 30 of the 347 men assigned to surgery ( 8.6 percent ) and 50 of the 348 men assigned to watchful waiting ( 14.4 percent ) , death was due to prostate cancer . The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years , for a relative risk of 0.56 ( 95 percent confidence interval , 0.36 to 0.88 ; P=0.01 by Gray 's test ) . For distant metastasis , the corresponding increase was from 1.7 to 10.2 percentage points , for a relative risk in the surgery group of 0.60 ( 95 percent confidence interval , 0.42 to 0.86 ; P=0.004 by Gray 's test ) , and for local progression , the increase was from 19.1 to 25.1 percentage points , for a relative risk of 0.33 ( 95 percent confidence interval , 0.25 to 0.44 ; P<0.001 by Gray 's test ) . CONCLUSIONS Radical prostatectomy reduces disease-specific mortality , overall mortality , and the risks of metastasis and local progression . The absolute reduction in the risk of death after 10 years is small , but the reductions in the risks of metastasis and local tumor progression are substantial Importance Underst and ing the adverse effects of contemporary approaches to localized prostate cancer treatment could inform shared decision making . Objective To compare functional outcomes and adverse effects associated with radical prostatectomy , external beam radiation therapy ( EBRT ) , and active surveillance . Design , Setting , and Participants Prospect i ve , population -based , cohort study involving 2550 men ( ⩽80 years ) diagnosed in 2011 - 2012 with clinical stage cT1 - 2 , localized prostate cancer , with prostate-specific antigen levels less than 50 ng/mL , and enrolled within 6 months of diagnosis . Exposures Treatment with radical prostatectomy , EBRT , or active surveillance was ascertained within 1 year of diagnosis . Main Outcomes and Measures Patient-reported function on the 26-item Exp and ed Prostate Cancer Index Composite ( EPIC ) 36 months after enrollment . Higher domain scores ( range , 0 - 100 ) indicate better function . Minimum clinical ly important difference was defined as 10 to 12 points for sexual function , 6 for urinary incontinence , 5 for urinary irritative symptoms , 5 for bowel function , and 4 for hormonal function . Results The cohort included 2550 men ( mean age , 63.8 years ; 74 % white , 55 % had intermediate- or high-risk disease ) , of whom 1523 ( 59.7 % ) underwent radical prostatectomy , 598 ( 23.5 % ) EBRT , and 429 ( 16.8 % ) active surveillance . Men in the EBRT group were older ( mean age , 68.1 years vs 61.5 years , P < .001 ) and had worse baseline sexual function ( mean score , 52.3 vs 65.2 , P < .001 ) than men in the radical prostatectomy group . At 3 years , the adjusted mean sexual domain score for radical prostatectomy decreased more than for EBRT ( mean difference , −11.9 points ; 95 % CI , −15.1 to −8.7 ) . The decline in sexual domain scores between EBRT and active surveillance was not clinical ly significant ( −4.3 points ; 95 % CI , −9.2 to 0.7 ) . Radical prostatectomy was associated with worse urinary incontinence than EBRT ( −18.0 points ; 95 % CI , −20.5 to −15.4 ) and active surveillance ( −12.7 points ; 95 % CI , −16.0 to −9.3 ) but was associated with better urinary irritative symptoms than active surveillance ( 5.2 points ; 95 % CI , 3.2 to 7.2 ) . No clinical ly significant differences for bowel or hormone function were noted beyond 12 months . No differences in health-related quality of life or disease-specific survival ( 3 deaths ) were noted ( 99.7%-100 % ) . Conclusions and Relevance In this cohort of men with localized prostate cancer , radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after 3 years and was associated with fewer urinary irritative symptoms than active surveillance ; however , no meaningful differences existed in either bowel or hormonal function beyond 12 months or in in other domains of health-related quality -of-life measures . These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer BACKGROUND Radical prostatectomy reduces mortality among men with clinical ly detected localized prostate cancer , but evidence from r and omized trials with long‐term follow‐up is sparse . METHODS We r and omly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow‐up data through 2017 . Cumulative incidence and relative risks with 95 % confidence intervals for death from any cause , death from prostate cancer , and metastasis were estimated in intention‐to‐treat and per‐ protocol analyses , and numbers of years of life gained were estimated . We evaluated the prognostic value of histopathological measures with a Cox proportional‐hazards model . RESULTS By December 31 , 2017 , a total of 261 of the 347 men in the radical‐prostatectomy group and 292 of the 348 men in the watchful‐waiting group had died ; 71 deaths in the radical‐prostatectomy group and 110 in the watchful‐waiting group were due to prostate cancer ( relative risk , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ; absolute difference in risk , 11.7 percentage points ; 95 % CI , 5.2 to 18.2 ) . The number needed to treat to avert one death from any cause was 8.4 . At 23 years , a mean of 2.9 extra years of life were gained with radical prostatectomy . Among the men who underwent radical prostatectomy , extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension , and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower ( scores range from 2 to 10 , with higher scores indicating more aggressive cancer ) . CONCLUSIONS Men with clinical ly detected , localized prostate cancer and a long life expectancy benefited from radical prostatectomy , with a mean of 2.9 years of life gained . A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer . ( Funded by the Swedish Cancer Society and others . Question In men with early prostate cancer , does radical prostatectomy reduce long-term mortality compared with watchful waiting ? Methods Design R and omized controlled trial ( RCT ) ( Sc and inavian Prostate Cancer Group Study Number 4 [ SPCG-4 ] ) . Allocation {Concealed}*. Blinding Blinded ( cause of death adjudicators ) . Follow-up period Median 23.6 years . Setting 14 centers in Sweden , Finl and , and Icel and . Patients 698 men < 75 years of age ( mean age 65 y , mean prostate specific antigen [ PSA ] level 13 ng/mL ) who had newly diagnosed , localized prostate cancer ( stages T0d , T1 , or T2 ) , highly to moderately highly differentiated tumor , PSA level < 50 ng/mL , and a negative bone scan . Exclusion criteria included life expectancy 10 years or other types of cancer . Intervention Radical prostatectomy ( n = 349 ) or watchful waiting ( n = 349 ) . Outcomes All-cause and prostate cancer mortality and distant metastases . Patient follow-up 99.6 % ( intention-to-treat analysis ) . Main results 85 % of men in the radical prostatectomy group and 8.3 % in the watchful waiting group had radical prostatectomy during the trial . The main results are in the Table . At 23 years , patients in the radical prostatectomy group gained a mean 2.9 extra years of life compared with those in the watchful-waiting group . Conclusion In early prostate cancer , radical prostatectomy reduced all-cause and prostate cancer mortality compared with watchful waiting at 23 years . Radical prostatectomy vs watchful waiting in early prostate cancer Outcomes Cumulative incidence at 23 y At 23 y Radical prostatectomy Watchful waiting RRR ( 95 % CI ) NNT ( CI ) All-cause mortality 72 % 84 % 26 % ( 13 to 38 ) 9 ( 6 to 19 ) Prostate cancer mortality 20 % 31 % 45 % ( 26 to 59 ) 9 ( 6 to 20 ) Distant metastases 27 % 43 % 46 % ( 30 to 58 ) 6 ( 5 to 11 ) Abbreviations defined in Glossary . RRR and CI calculated from relative risks and CIs in article . Accounts for competing risks for death in prostate cancer mortality analysis and competing risks for death without previous metastases in distant metastases analysis . RRR based on data over trial follow-up period ( median 23.6 y ) . NNT based on estimates at 23 y. Commentary The 23-year outcomes of SPCG-4 provide the central evidence for the role of radical prostate surgery in treating clinical ly localized prostate cancer . In terms of relative effectiveness for disease-specific mortality , results of SPCG-4 align with those of the Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) ( 1 ) and even those of the more recent Prostate Testing for Cancer and Treatment ( ProtecT ) trial , which used active monitoring rather than watchful waiting ( 2 ) . These 3 trials differed in length of follow-up ; methods ; and most important , the natural history of the cancer detected and patients ' baseline risk for dying of prostate cancer . As Bill-Axelson and colleagues emphasized , the absolute 12 % reduction in prostate cancer mortality and mean 2.9 years of life gained with radical prostatectomy was related specifically to men with clinical ly detected prostate cancer and can not be directly applied to men with PSA-detected prostate cancer . Since SPCG-4 and PIVOT were initiated , the paradigm of prostate cancer early detection has changed . The added lead time result ing from current screening methods makes it unlikely that today 's patients will experience the absolute mortality benefits achieved in the trials ; the number-needed-to-treat to achieve any mortality reduction will be markedly higher , and benefit will take considerably longer to achieve . It would be misguided to use the SPCG-4 findings to implement more intensified prostate cancer screening or more aggressive treatment of PSA-detected prostate cancer . Aggressive treatment should be limited to patients with a substantial burden of high- grade ( Gleason grade 4 ) disease and an estimated life expectancy 15 years Importance Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects . Objective To compare quality of life ( QOL ) after radical prostatectomy , external beam radiotherapy , and brachytherapy vs active surveillance . Design , Setting , and Participants Population -based prospect i ve cohort of 1141 men ( 57 % participation among eligible men ) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry . Median time from diagnosis to enrollment was 5 weeks , and all men were enrolled with written informed consent prior to treatment . Final follow-up date for current analysis was September 9 , 2015 . Exposures Treatment with radical prostatectomy , external beam radiotherapy , brachytherapy , or active surveillance . Main Outcomes and Measures Quality of life using the vali date d instrument Prostate Cancer Symptom Indices was assessed at baseline ( pretreatment ) and 3 , 12 , and 24 months after treatment . The instrument contains 4 domains — sexual dysfunction , urinary obstruction and irritation , urinary incontinence , and bowel problems — each scored from 0 ( no dysfunction ) to 100 ( maximum dysfunction ) . Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point . Results Of 1141 enrolled men , 314 pursued active surveillance ( 27.5 % ) , 469 radical prostatectomy ( 41.1 % ) , 249 external beam radiotherapy ( 21.8 % ) , and 109 brachytherapy ( 9.6 % ) . After propensity weighting , median age was 66 to 67 years across groups , and 77 % to 80 % of participants were white . Across groups , propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction , 20.8 to 22.8 for urinary obstruction and irritation , 9.7 to 10.5 for urinary incontinence , and 5.7 to 6.1 for bowel problems . Compared with active surveillance , mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy ( 36.2 [ 95 % CI , 30.4 - 42.0 ] ) , external beam radiotherapy ( 13.9 [ 95 % CI , 6.7 - 21.2 ] ) , and brachytherapy ( 17.1 [ 95 % CI , 7.8 - 26.6 ] ) . Compared with active surveillance at 3 months , worsened urinary incontinence was associated with radical prostatectomy ( 33.6 [ 95 % CI , 27.8 - 39.2 ] ) ; acute worsening of urinary obstruction and irritation with external beam radiotherapy ( 11.7 [ 95 % CI , 8.7 - 14.8 ] ) and brachytherapy ( 20.5 [ 95 % CI , 15.1 - 25.9 ] ) ; and worsened bowel symptoms with external beam radiotherapy ( 4.9 [ 95 % CI , 2.4 - 7.4 ] ) . By 24 months , mean scores between treatment groups vs active surveillance were not significantly different in most domains . Conclusions and Relevance In this cohort of men with localized prostate cancer , each treatment strategy was associated with distinct patterns of adverse effects over 2 years . These findings can be used to promote treatment decisions that incorporate individual preferences BACKGROUND We evaluated symptoms and self- assessment s of quality of life in men with localized prostate cancer who participated in a r and omized comparison between radical prostatectomy and watchful waiting . METHODS Between 1989 and 1999 , a group of Swedish urologists r and omly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting . In this follow-up study , we obtained information from 326 of 376 eligible men ( 87 percent ) concerning certain symptoms , symptom-induced distress , well-being , and the subjective assessment of quality of life by means of a mailed question naire . RESULTS Erectile dysfunction ( 80 percent vs. 45 percent ) and urinary leakage ( 49 percent vs. 21 percent ) were more common after radical prostatectomy , whereas urinary obstruction ( e.g. , 28 percent vs. 44 percent for weak urinary stream ) was less common . Bowel function , the prevalence of anxiety , the prevalence of depression , well-being , and the subjective quality of life were similar in the two groups . CONCLUSIONS The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction , urinary leakage , and urinary obstruction , but on average , the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years Importance In the United States , the lifetime risk of being diagnosed with prostate cancer is approximately 13 % , and the lifetime risk of dying of prostate cancer is 2.5 % . The median age of death from prostate cancer is 80 years . Many men with prostate cancer never experience symptoms and , without screening , would never know they have the disease . African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men . Objective To up date the 2012 US Preventive Services Task Force ( USPSTF ) recommendation on prostate-specific antigen (PSA)–based screening for prostate cancer . Evidence Review The USPSTF review ed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer . The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening . The review s also examined the benefits and harms of PSA-based screening in patient sub population s at higher risk of prostate cancer , including older men , African American men , and men with a family history of prostate cancer . Findings Adequate evidence from r and omized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened . Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened . Potential harms of screening include frequent false-positive results and psychological harms . Harms of prostate cancer treatment include erectile dysfunction , urinary incontinence , and bowel symptoms . About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence , and 2 in 3 men will experience long-term erectile dysfunction . Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results , diagnostic harms from biopsies , and harms from treatment . The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men . How each man weighs specific benefits and harms will determine whether the overall net benefit is small . The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms . Conclusions and Recommendation For men aged 55 to 69 years , the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician . Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men . However , many men will experience potential harms of screening , including false-positive results that require additional testing and possible prostate biopsy ; overdiagnosis and overtreatment ; and treatment complications , such as incontinence and erectile dysfunction . In determining whether this service is appropriate in individual cases , patients and clinicians should consider the balance of benefits and harms on the basis of family history , race/ethnicity , comorbid medical conditions , patient values about the benefits and harms of screening and treatment-specific outcomes , and other health needs . Clinicians should not screen men who do not express a preference for screening . ( C recommendation ) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older . ( D recommendation BACKGROUND Robust data on patient-reported outcome measures comparing treatments for clinical ly localized prostate cancer are lacking . We investigated the effects of active monitoring , radical prostatectomy , and radical radiotherapy with hormones on patient-reported outcomes . METHODS We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment ( ProtecT ) trial who completed question naires before diagnosis , at 6 and 12 months after r and omization , and annually thereafter . Patients completed vali date d measures that assessed urinary , bowel , and sexual function and specific effects on quality of life , anxiety and depression , and general health . Cancer-related quality of life was assessed at 5 years . Complete 6-year data were analyzed according to the intention-to-treat principle . RESULTS The rate of question naire completion during follow-up was higher than 85 % for most measures . Of the three treatments , prostatectomy had the greatest negative effect on sexual function and urinary continence , and although there was some recovery , these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial . The negative effect of radiotherapy on sexual function was greatest at 6 months , but sexual function then recovered somewhat and was stable thereafter ; radiotherapy had little effect on urinary continence . Sexual and urinary function declined gradually in the active-monitoring group . Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat , except for the increasing frequency of bloody stools ; bowel function was unchanged in the other groups . Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months . Effects on quality of life mirrored the reported changes in function . No significant differences were observed among the groups in measures of anxiety , depression , or general health-related or cancer-related quality of life . CONCLUSIONS In this analysis of patient-reported outcomes after treatment for localized prostate cancer , patterns of severity , recovery , and decline in urinary , bowel , and sexual function and associated quality of life differed among the three groups . ( Funded by the U.K. National Institute for Health Research Health Technology Assessment Program ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only . Uncertainty persists regarding nonfatal health outcomes and long‐term mortality . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer to radical prostatectomy or observation . We extended follow‐up through August 2014 for our primary outcome , all‐cause mortality , and the main secondary outcome , prostate‐cancer mortality . We describe disease progression , treatments received , and patient‐reported outcomes through January 2010 ( original follow‐up ) . RESULTS During 19.5 years of follow‐up ( median , 12.7 years ) , death occurred in 223 of 364 men ( 61.3 % ) assigned to surgery and in 245 of 367 ( 66.8 % ) assigned to observation ( absolute difference in risk , 5.5 percentage points ; 95 % confidence interval [ CI ] , ‐1.5 to 12.4 ; hazard ratio , 0.84 ; 95 % CI , 0.70 to 1.01 ; P=0.06 ) . Death attributed to prostate cancer or treatment occurred in 27 men ( 7.4 % ) assigned to surgery and in 42 men ( 11.4 % ) assigned to observation ( absolute difference in risk , 4.0 percentage points ; 95 % CI , ‐0.2 to 8.3 ; hazard ratio , 0.63 ; 95 % CI , 0.39 to 1.02 ; P=0.06 ) . Surgery may have been associated with lower all‐cause mortality than observation among men with intermediate‐risk disease ( absolute difference , 14.5 percentage points ; 95 % CI , 2.8 to 25.6 ) but not among those with low‐risk disease ( absolute difference , 0.7 percentage points ; 95 % CI , ‐10.5 to 11.8 ) or high‐risk disease ( absolute difference , 2.3 percentage points ; 95 % CI , ‐11.5 to 16.1 ) ( P=0.08 for interaction ) . Treatment for disease progression was less frequent with surgery than with observation ( absolute difference , 26.2 percentage points ; 95 % CI , 19.0 to 32.9 ) ; treatment was primarily for asymptomatic , local , or biochemical ( prostate‐specific antigen ) progression . Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years . Disease‐related or treatment‐related limitations in activities of daily living were greater with surgery than with observation through 2 years . CONCLUSIONS After nearly 20 years of follow‐up among men with localized prostate cancer , surgery was not associated with significantly lower all‐cause or prostate‐cancer mortality than observation . Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression , mostly for asymptomatic , local , or biochemical progression . ( Funded by the Department of Veterans Affairs and others ; PIVOT Clinical Trials.gov number , NCT00007644 . New research suggests that in patients with localised prostate cancer , prostatectomy does not significantly reduce all-cause mortality or prostate cancer mortality , when compared with observation , over a 20-year follow-up . Timothy Wilt ( University of Minnesota School of Medicine , Minneapolis , MN , USA ) and colleagues report long-term follow-up results from the r and omised , controlled Prostate Cancer Intervention versus Observation Trial ( PIVOT ) . The research ers r and omly assigned 731 patients to radical prostatectomy ( n=364 ) or observation ( n=367 ) . 12-year follow-up results showed that radical prostatectomy did not reduce all-cause mortality or prostate cancer mortality when compared with observation . In the 20-year follow-up results of PIVOT , the cumulative incidence of any-cause death was 61·3 % ( 95 % CI 56·2–66·1 ) in patients who had prostatectomy and 66·8 % ( 61·8–71·4 ) in those who received observation ( relative risk [ RR ] 0·92 , 95 % CI 0·82–1·02 ) . Cumulative incidence of death due to prostate cancer or treatment was 7·4 % ( 95 % CI 5·2–10·6 ) in patients who had prostatectomy and 11·4 % ( 8·6–15·1 ) in those who received observation ( RR 0·65 , 95 % CI 0·41–1·03 ) . In intermediate-risk patients , all-cause mortality was lower in patients who had prostatectomy than in those who did not ( hazard ratio 0·68 , 95 % CI 0·50–0·92 ) but this did not hold true for patients with low-risk disease ( 0·98 , 0·72–1·33 ) or high-risk disease ( 0·78 , 0·54–1·13 ; p=0·08 ) . For patient-reported outcomes with the short form health survey SF-12 , prostatectomy , when compared with observation , was associated with increased urinary incontinence , sexual and erectile disorders , and limitations in activities of daily living . Coauthor Michael Barry ( Massachusetts General Hospital , Boston , MA , USA ) commented : “ Observation results in a similar length of life [ compared with surgery ] , avoids prostate cancer death , and prevents surgical harms . ” According to Kari Tikkinen ( University of Helsinki , Helsinki , Finl and ) , the study “ shows that risk of death from prostate cancer is low among men with early-stage prostate cancer treated with observation . ” Ian Haines ( Monash University , Melbourne , VIC , Australia ) added that the study reveals the natural history of prostate cancer and confirms that “ radical treatment does not save lives or change the natural history in a clinical ly meaningful way . BACKGROUND The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer r and omly allocated to active monitoring ( AM ) , radical prostatectomy , and external beam radiotherapy . OBJECTIVE To report outcomes according to treatment received in men in r and omised and treatment choice cohorts . DESIGN , SETTING , AND PARTICIPANTS This study focuses on secondary care . Men with clinical ly localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM , radical prostatectomy , and radiotherapy . INTERVENTION Two cohorts included 1643 men who agreed to be r and omised and 997 who declined r and omisation and chose treatment . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Analysis was carried out to assess mortality , metastasis and progression and health-related quality of life impacts on urinary , bowel , and sexual function using patient-reported outcome measures . Analysis was based on comparisons between groups defined by treatment received for both r and omised and treatment choice cohorts in turn , with pooled estimates of intervention effect obtained using meta- analysis . Differences were estimated with adjustment for known prognostic factors using propensity scores . RESULTS AND LIMITATIONS According to treatment received , more men receiving AM died of PCa ( AM 1.85 % , surgery 0.67 % , radiotherapy 0.73 % ) , whilst this difference remained consistent with chance in the r and omised cohort ( p=0.08 ) ; stronger evidence was found in the exploratory analyses ( r and omised plus choice cohort ) when AM was compared with the combined radical treatment group ( p=0.003 ) . There was also strong evidence that metastasis ( AM 5.6 % , surgery 2.4 % , radiotherapy 2.7 % ) and disease progression ( AM 20.35 % , surgery 5.87 % , radiotherapy 6.62 % ) were more common in the AM group . Compared with AM , there were higher risks of sexual dysfunction ( 95 % at 6mo ) and urinary incontinence ( 55 % at 6mo ) after surgery , and of sexual dysfunction ( 88 % at 6mo ) and bowel dysfunction ( 5 % at 6mo ) after radiotherapy . The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa . CONCLUSIONS Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment , and stronger evidence of greater PCa mortality in the AM group . PATIENT SUMMARY More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10yr , irrespective of whether treatment is by means of monitoring , surgery , or radiotherapy . Side effects on sexual and bladder function are better after active monitoring , but the risks of spreading of prostate cancer are more common |
527 | 25,632,999 | CONCLUSION The r and om-effects meta- analysis based on RCTs suggests that TCSs reduced the risk of SSI by 26 % among patients undergoing surgery .
This effect was particularly evident among those who underwent abdominal surgery | OBJECTIVE To analyze available evidence on the effectiveness of triclosan-coated sutures ( TCSs ) in reducing the risk of surgical site infection ( SSI ) . | BACKGROUND Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery , and triclosan-coated sutures were developed to reduce their occurrence . The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure , compared with non-coated PDS II sutures , in the prevention of surgical site infections . METHODS This multicentre , r and omised controlled group-sequential superiority trial was done in 24 German hospitals . Adult patients ( aged ≥18 years ) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion . Exclusion criteria were impaired mental state , language problems , and participation in another intervention trial that interfered with the intervention or outcome of this trial . A central web-based r and omisation tool was used to r and omly assign eligible participants by permuted block r and omisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures ( PDS Plus ) or uncoated sutures ( PDS II ) for abdominal fascia closure . The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation . Patients , surgeons , and the outcome assessors were masked to group assignment . Interim and final analyses were by modified intention to treat . This trial is registered with the German Clinical Trials Register , number DRKS00000390 . FINDINGS Between April 7 , 2010 , and Oct 19 , 2012 , 1224 patients were r and omly assigned to intervention groups ( 607 to PDS Plus , and 617 to PDS II ) , of whom 1185 ( 587 PDS Plus and 598 PDS II ) were analysed by intention to treat . The study groups were well balanced in terms of patient and procedure characteristics . The occurrence of surgical site infections did not differ between the PDS Plus group ( 87 [ 14·8 % ] of 587 ) and the PDS II group ( 96 [ 16·1 % ] of 598 ; OR 0·91 , 95 % CI 0·66 - 1·25 ; p=0·64 ) . Serious adverse events also did not differ between the groups-146 of 583 ( 25·0 % ) patients treated with PDS Plus had at least one serious adverse event , compared with 138 of 602 ( 22·9 % ) patients treated with PDS II ; p=0·39 ) . INTERPRETATION Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy . Innovative , multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections . FUNDING Johnson & Johnson Medical Limited OBJECTIVES The incidence of surgical site infection ( SSI ) after open vein harvesting in coronary artery bypass grafting ( CABG ) patients ranges in different studies between 2 and 20 % . Triclosan is an antibacterial substance that reduces the growth of bacteria by inhibiting fatty acid synthesis . We hypothesized that wound closure with triclosan-coated sutures would reduce SSI after open vein harvesting . METHODS An investigator-initiated prospect i ve r and omized double-blind single-centre study was performed with 374 patients , r and omized to subcutaneous and intracutaneous leg-wound closure with either triclosan-coated sutures ( Vicryl Plus ® and Monocryl Plus ® , Ethicon , Somerville , NJ , USA ) ( n = 184 ) or identical sutures without triclosan ( n = 190 ) from the same manufacturer . All patients were followed up after 30 days ( clinical visit ) and 60 days ( telephone interview ) . Primary endpoint was SSI within 60 days after surgery according to the definition of Center for Disease Control . Predefined secondary endpoints included culture-proven and antibiotic-treated SSI . RESULTS The primary endpoint occurred in 23 patients ( 12.5 % ) with triclosan-coated sutures and in 38 patients ( 20.0 % ) in the group without triclosan ( P = 0.0497 , risk ratio 0.63 , ( 95 % confidence interval 0.39–1.00 ) . Corresponding figures for culture-proven infections were 7.6 vs 12.1 % , ( P = 0.15 ) , and for antibiotic-treated infections , 10.9 vs 18.4 % , ( P = 0.039 ) . Staphylococcus aureus and coagulase-negative staphylococci were the most common pathogens in both groups . Insulin-treated diabetes and vein-harvesting time were associated with SSI after vein harvesting . CONCLUSIONS Leg-wound closure with triclosan-coated sutures in CABG patients reduces SSIs after open vein harvesting . ( Clinical Trials.gov number NCT01212315 ) OBJECT Implantation of cerebrospinal fluid ( CSF ) shunting devices is associated with a 5 - 15 % risk of infection as cited in contemporary pediatric neurosurgical literature . Shunt infections typically require complete removal of the device and prolonged antibiotic treatment followed by shunt replacement . Moreover , shunt infections are commonly associated with prolonged hospital stays , potential comorbidity , and the increased risk of neurological compromise due to ventriculitis or surgical complications . The authors prospect ively evaluated the incidence of CSF shunt infection following shunt procedures performed using either antimicrobial suture ( AMS ) or conventional suture . METHODS In a single-center , prospect i ve , double-blinded , r and omized controlled trial , the authors enrolled 61 patients , among whom 84 CSF shunt procedures were performed over 21 months . R and omization to the study ( AMS ) or control ( placebo ) group was stratified to minimize the effect of known shunt infection risk factors on the findings . Antibacterial shunt components were not used . The primary outcome measure was the incidence of shunt infection within 6 months of surgery . RESULTS The shunt infection rate in the study group was 2 ( 4.3 % ) of 46 procedures and 8 ( 21 % ) of 38 procedures in the control group ( p = 0.038 ) . There were no statistically significant differences in shunt infection risk factors between the groups ( procedure type and time , age < 6 months , weight < 4 kg , recent history of shunt infection ) . No suture-related adverse events were reported in either group . CONCLUSIONS These results support the suggestion that the use of AMS for CSF shunt surgery wound closure is safe , effective , and may be associated with a reduced risk of postoperative shunt infection . A larger r and omized controlled trial is needed to confirm this association BACKGROUND Surgical site infection ( SSI ) is the fourth commonest healthcare-associated infection and complicates at least 5 % of open operations . In a r and omized clinical trial , antimicrobial-coated sutures were compared with their conventional counterparts , polyglactin and poliglecaprone , for skin closure after breast cancer surgery to assess their role in reducing the rate of SSI . METHODS Between November 2008 and February 2011 , 150 female patients presenting with breast cancer to a single center were r and omized to skin closure with antimicrobial-coated or plain sutures . Postoperatively , SSI was defined using the U.S. Centers for Disease Control and Prevention ( CDC ) definitions and scored using the ASEPSIS or Southampton systems by trained , blinded observers with close post-discharge surveillance and patient diaries . Surgeons and patients were blinded to the type of suture used . RESULTS Using CDC criteria , the overall rate of SSI was 18.9 % at six weeks . Six patients ( 4.7 % ) needed intervention or readmission for SSI . Skin closure with antimicrobial sutures showed a non-statistically significant reduction in the SSI rate , to 15.2 % , compared with conventional sutures ( 22.9 % ) . A uniform tendency for fewer SSIs in the antimicrobial-coated suture group was found using ASEPSIS and Southampton scores , but again , the difference was not statistically significant . CONCLUSION The previously reported high rate of SSI related to breast surgery was confirmed . Using statistical modeling and earlier reports , the study was powered to show a difference using ASEPSIS scores , but the modification used in this trial failed to find a difference . Finding a statistically significant difference would have needed two to three times the number of patients recruited . Further evaluation of antimicrobial-coated sutures is merited , particularly if used as part of a care bundle to reduce SSI after breast cancer surgery BACKGROUND The primary objective of this multicenter post-market study was to compare the cosmetic outcome of triclosan-coated VICRYL Plus sutures with Chinese silk sutures for skin closure of modified radical mastectomy . A secondary objective was to assess the incidence of surgical site infection ( SSI ) . METHODS Patients undergoing modified radical mastectomy were r and omly assigned to coated VICRYL Plus antibacterial ( Polyglactin 910 ) suture or Chinese silk suture . Cosmetic outcomes were evaluated postoperatively at days 12 ( ± 2 ) and 30 ( ± 5 ) , and the evidence of SSI was assessed at days 3 , 5 , 7 , 12 ( ± 2 ) , 30 ( ± 5 ) , and 90 ( ± 7 ) . Cosmetic outcomes were independently assessed via visual analogue scale ( VAS ) score evaluations of blinded incision photographs ( primary endpoint ) and surgeon-assessed modified Holl and er Scale ( mHCS ) scores ( secondary endpoint ) . SSI assessment s used both CDC criteria and ASEPSIS scores . RESULTS Six Chinese hospitals r and omized 101 women undergoing modified radical mastectomy to closure with coated VICRYL Plus suture ( n = 51 ) or Chinese silk suture ( n = 50 ) . Mean VAS cosmetic outcome scores for antibacterial suture ( 67.2 ) were better than for Chinese silk ( 45.4 ) at day 30 ( P < 0.0001 ) ) . Mean mHCS cosmetic outcome total scores , were also higher for antibacterial suture ( 5.7 ) than for Chinese silk ( 5.0 ) at day 30 ( P = 0.002 ) . CONCLUSIONS Patients using coated VICRYL Plus suture had significantly better cosmetic outcomes than those with Chinese silk sutures . Patients using coated VICRYL Plus suture had a lower SSI incidence compared to the Chinese silk sutures , although the difference did not reach statistical significance OBJECTIVE To evaluate the efficacy and safety of new antibacterial suture ( Vicryl Plus ) compared with a traditional braided suture ( Vicryl ) in a clinical study . The primary goal was to study effectiveness on reduced surgical site infection in an appendectomy operation . The authors ' secondary goal was to analyze the safety and physical properties of Vicryl plus . MATERIAL AND METHOD This was a prospect i ve , r and omized , controlled , double blind , comparative , single-center study . After appendectomy was done , the patients were r and omized in two groups : Vicryl Plus and Vicryl to selected suture for suturing the abdominal sheath . The surgical site infection was evaluated for 30 days , 6 months , and 1 year . The surgeons and attending doctor were blind to the type of suture . This is the primary report of the first 100 patients . RESULTS There was no difference in demographic and preoperative clinical in both groups . Although there was no statistical difference in the surgical site infection of Vicryl and Vicryl Plus ( 8 and 10 % , p = 0.05 ) , one case of deep surgical site infection was detected in the Vicryl group . No complications and no difference in related suture material s were detected . CONCLUSION Coated polyglactin 910 with tricosan ( Vicryl Plus ) is safe and satisfactory in surgical practice . Surgical site infection of appendectomy seemed too to be comparable between coated polyglactin 910 with tricosan ( Vicryl Plus ) and traditional polyglactin 910 ( Vicryl ) group BACKGROUND Surgical wound infection is a common complication , which increases the hospital stay and costs after surgery for head and neck cancer . In this study , we evaluated the effect of Triclosan-coated sutures on surgical wounds and analyzed the risk factors for wound infections in head and neck cancer surgery . PATIENTS AND METHODS From January 2007 to December 2009 , 253 consecutive patients underwent wide excision of a head or neck cancer and reconstructive procedures . All patient data were collected prospect ively . Of these , 241 patients were included in this study , divided into two groups . The Triclosan group contained 112 patients , whose surgical wounds were closed with Triclosan-coated sutures ( Vicryl Plus ) . The control group included the remaining 129 patients , whose surgical wounds were closed with conventional Vicryl sutures . We conducted a retrospective , multivariate analysis to determine independent risk factors for the cervical wound infection . RESULTS The cervical wound infection rate was 14.9 % ( 17/112 ) in the Triclosan group and 14.7 % ( 19/129 ) in the control group , and these rates were not significantly different . Tumour stage and delayed intra-oral flap healing were independent risk factors for cervical wound infection . CONCLUSIONS In this preliminary study , Triclosan-coated Vicryl sutures did not reduce the infection rate of cervical wounds after head or neck cancer surgery . The effectiveness of this suture material in head and neck cancer surgery should be considered with caution OBJECTIVE Postoperative surgical site infections ( SSI ) still greatly affect mortality and morbidity in cardiovascular surgery . SSI may be related to the suture material . In this prospect i ve , r and omized , controlled , and double-blinded study , the effect of antibacterial suture material on SSI in cardiac surgical patients was investigated . METHODS We r and omly allocated 510 patients into 2 groups . Antibacterial suture material s were used for wound closure in 170 patients ( triclosan-coated suture group ) , and routine suture material s were used in 340 patients ( noncoated suture group ) . All patients were evaluated for SSI on days 10 , 20 , and 30 following cardiac surgery . RESULTS Preoperative risk factors and laboratory findings were comparable for the 2 groups . Sternal infection occurred in 4 ( 2.4 % ) of the patients in the triclosan-coated suture group and in 3.5 % of the noncoated suture group ( P > .05 ) . Leg wound infection occurred in 5 ( 3.5 % ) of the patients in the triclosan-coated suture group and in 3.8 % of the noncoated suture group ( P > .05 ) . Only diabetes mellitus was an independent predictor of SSI . CONCLUSION Both noncoated and triclosan-coated suture material s are safe . Larger studies may be needed to show the benefit and cost-effectiveness , if any , of triclosan-coated material s over noncoated material OBJECTIVES Leg wound infection is a common complication after coronary artery bypass grafting ( CABG ) . Suture contamination has been suggested as a mechanism of surgical site infections . Vicryl Plus ( ® ) is a polyglacitin suture coated with the antiseptic chemical substance Triclosan , which has been shown to inhibit the growth of Staphylococcus aureus in vitro . The first aim of the present study was to compare Vicryl Plus with conventional Vicryl ( ® ) sutures with regard to leg wound infections following CABG . The second aim was to examine patient- and operative characteristics , which are assumed to predict leg wound infections . METHODS After statistical calculations a priori , 328 CABG patients were prospect ively r and omized to leg wound closure with Vicryl Plus ( 164 patients ) or conventional Vicryl sutures ( 164 patients ) . Incidences of leg wound infection and predictors of infection related to patient- and operative characteristics were examined . RESULTS The incidence of leg wound infections was 10.4 % ( 17/163 ) in the Vicryl group , and 10.0 % ( 16/160 ) in the Vicryl Plus group ( P = 1.00 ) . Patients with leg wound infections had increased body mass index and prolonged extracorporeal circulation and aortic clamping time compared with patients without infections . CONCLUSIONS In the present study , we report for the first time that Vicryl Plus did not reduce the incidence of leg wound infections in patients undergoing CABG . Obesity and prolonged time of extracorporeal circulation were both associated with the increased risk of infections . Currently , the clinical role and indication for the use of Vicryl Plus have yet to be defined This study compared Triclosan coated polyglactin 910 ( Vicryl * Plus ) with polyglactin 910 ( Vicryl * ) on abdominal wall healing in colorectal surgery patients . 184 patients with colorectal cancer were included in the study . In 91 , the abdominal wall was closed with the Vicryl * Plus , and in 93 patients with Vicryl*. Demographic characteristics , biochemical inflammatory parameters , wound appearance , length of hospital stay , postoperative wound complications and post-incisional hernia were recorded . In the Vicryl * Plus group there was a shorter hospital stay ( 13.2 + /- 1.3 days ; 21.4 + /- 2.8 respectively ) . In the Vicryl * Plus group inflammatory parameters decreased to normal within the first week whereas in the Vicryl * group remained increased . In the Vicryl * Plus group four patients had a wound discharge , seven had inflammatory reactions to the skin sutures . One dehiscence was noticed . In the Vicryl * group 12 patients had an SSI , 14 patients had inflammatory reactions to the skin sutures and 7 patients had a wound dehiscence . Closure of the abdominal wall using Vicryl * Plus decreases postoperative wound complications , length of hospital stay and is associated with a more rapid return of inflammatory markers to normal Objectives Wound infections after abdominal surgery are still frequent types of nosocomial infections . Suture material s might serve as a vehicle for mechanical transport of bacteria into the surgical wound . To reduce bacterial adherence to surgical sutures , triclosan-coated polyglactin 910 suture material s with antiseptic activity ( Vicryl plus ® ) were developed . The aim of this prospect i ve non-r and omized clinical pathway driven study was to ascertain if the use of Vicryl plus ® reduced the number of wound infections after transverse laparotomy . Patients and methods Between October 2003 and October 2007 , 839 operations were performed using a transverse abdominal incision . In the first time period , a PDSII ® loop suture was used for abdominal wall closure . In the second time period , we used Vicryl plus ® . Risk factors were collected prospect ively to compare the two groups . Results Using a PDSII ® loop suture for abdominal wall closure in the first time period , 9.2 % of the patients developed wound infections . In the second time period , using Vicryl plus ® , the number of wound infections decreased to 4.3 % ( p < 0,005 ) . Both groups were comparable regarding risk factors despite no other changes in protocol s of patient care . Conclusion Antiseptic-coated loop Vicryl suture for abdominal wall closure can be superior to PDSII sutures in respect to the development of wound infections after a two-layered closure of transverse laparotomy BACKGROUND Coated polyglactin 910 suture with triclosan was developed recently in order to imbue the parent suture , coated polyglactin 910 , with antibacterial activity against the most common organisms that cause surgical site infections ( SSI ) . Because such alterations could alter the physical properties of the suture , this study sought to compare the intraoperative h and ling and wound healing characteristics of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture in pediatric patients undergoing various general surgical procedures . METHODS This was a prospect i ve , r and omized , controlled , open-label , comparative , single-center study . Pediatric patients ( age 1 - 18 years ) undergoing various surgical procedures were r and omized in a 2:1 ratio to treatment with either coated polyglactin 910 suture with triclosan or coated polyglactin 910 suture . The primary endpoint was the surgeon 's assessment of the overall intraoperative h and ling of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture without triclosan . The secondary endpoints included specific intraoperative suture h and ling measures and wound healing assessment s. The suture h and ling measures were ( 1 ) ease of passage through tissue ; ( 2 ) first-throw knot holding ; ( 3 ) knot tie-down smoothness ; ( 4 ) knot security ; ( 5 ) surgical h and ling ; ( 6 ) surgical h and ; ( 7 ) memory ; and ( 8) suture fraying . Assessment of wound healing included the following : Healing progress , infection , edema , erythema , skin temperature , seroma , suture sinus , and pain . Adverse events were recorded . RESULTS Scores for intraoperative h and ling were favorable and not significantly different for both sutures , although coated polyglactin 910 suture with triclosan received more " excellent " scores ( 71 % vs. 59 % ) . Wound healing characteristics were comparable for both sutures except for pain on postoperative day 1 . Significantly fewer patients treated with polyglactin 910 suture with triclosan reported pain on day 1 than patients who received the other suture ( 68 % vs. 89 % , p = 0.01 ) . The overall incidence of adverse events was 18 % ; none was devicerelated . CONCLUSIONS Coated polyglactin 910 suture with triclosan performed as well or better than traditional coated polyglactin 910 suture in pediatric patients undergoing general surgical procedures . The incidence of postoperative pain was significantly less in patients treated with coated polyglactin 910 suture with triclosan than the traditional suture . We speculate that polyglactin 910 suture with triclosan , by inhibiting bacterial colonization of the suture , reduced pain that can be an indicator of " sub clinical " infection . Coated polyglactin 910 suture with triclosan may be a useful alternative in patients at increased risk of developing SSI BACKGROUND Wound infection and dehiscence are both major contributors to postoperative morbidity . One potential cause or co-factor is the use of suture material . A recently introduced subcutaneous suture is coated with triclosan ( TC ) , an antiseptic drug . It is suggested to reduce wound complications . METHODS To investigate the effect of TC on wound healing a double blind prospect i ve pilot study in women undergoing a breast reduction was performed . Each patient was her own control . After r and omisation the TC-coated sutures were used either on the left or right side . The contralateral side was used as the control . The incidence of dehiscence was studied . RESULTS Twenty-six patients were included . In the TC breasts there was a wound dehiscence in 16 cases , whereas in the control breasts in seven cases a dehiscence was observed ( P=0.023 ) . CONCLUSION These results suggest that TC-coated sutures should be used with caution . These sutures have already been introduced on to the market without good clinical studies and might have potential adverse effects as shown by these data BACKGROUND In colorectal surgeries , surgical site infections ( SSIs ) frequently cause morbidity ; an incidence of up to 20 % has been shown in previous studies . Recently , to prevent microbial colonization of suture material in operative wounds , triclosan-coated polyglactin suture material s with antimicrobial activity have been developed ; however , their significance in colorectal surgery remains unclear . This r and omized controlled trial was conducted to assess the value of triclosan-coated polyglactin sutures in colorectal surgery . METHODS A total of 410 consecutive patients who had undergone elective colorectal operations were enrolled in this trial . Of those patients , the 206 in the study group underwent wound closure with triclosan-coated polyglactin 910 antimicrobial sutures , and the 204 patients in the control group received conventional wound closures with polyglactin 910 sutures . RESULTS The study group and the control group were comparable regarding risk factors for SSIs . The incidence of wound infection in the study group was 9 of 206 patients ( 4.3 % ) , and that in the control group was 19 of 204 patients ( 9.3 % ) . The difference is statistically significant in the 2 groups ( P = .047 ) . The median additional cost of wound infection management was $ 2,310 . The actual entire additional cost , therefore , of 9 patients in the study group was $ 18,370 , and that of 19 patients in the control group was $ 60,814 . CONCLUSION Triclosan-coated sutures can reduce the incidence of wound infections and the costs in colorectal surgery Background Surgical wound infection ( SWI ) is a common complication after peripheral vascular surgery . In a prospect i ve study , triclosan-coated sutures were reported to decrease the incidence of surgical site infection after various surgical procedures . The aim of our study was to test the hypothesis that use of triclosan-coated sutures decreases the incidence of SWI after lower limb vascular surgery . Methods This prospect i ve , r and omized , multicenter , double-blinded trial was conducted between July 2010 and January 2011 in five hospitals in Finl and . We r and omly allocated 276 patients undergoing lower limb revascularization surgery to a study ( n = 139 ) or a control ( n = 137 ) group . Surgical wounds in the study group were closed with triclosan-coated suture material , and wounds in the control group were closed with noncoated sutures . The main outcome measure was SWI . A surgical wound complication was considered to be an infection if there were bacteria isolated from the wound or if there were areas of localized redness , heat , swelling , and pain around the wound appearing within 30 days after the operative procedure . Logistic regression analysis was used to assess the independent effect of triclosan-coated sutures on the incidence of SWI . Results Altogether , 61 ( 22.1 % ) patients developed SWI . SWI occurred in 31 ( 22.3 % ) patients in the study group and in 30 ( 21.9 % ) patients in the control group ( odds ratio 1.10 , 95 % confidence interval 0.61–2.01 , p = 0.75 . ) Conclusions The use of triclosan-coated sutures does not reduce the incidence of SWI after lower limb vascular surgery BACKGROUND Surgical site infections ( SSI ) are the third most common hospital-acquired infections and account for 14 % to 16 % of all such infections . In elective colorectal operations , the international SSI rate ranges from 4.7%-25 % . In a previous retrospective study in this department , the SSI rate was unacceptably high ( 25 % ) , and the promising different international evaluations of triclosan-coated suture material s encouraged us to create a multicenter r and omized trial to improve our results . The main goal of this study was to compare triclosan-coated and uncoated absorbable suture ( PDS Plus ( ® ) with PDS II ( ® ) ) in elective colorectal operations . METHODS This was an internet-based study involving seven surgical centers . All the elective colorectal operations were performed by experienced surgeons . For abdominal fascia closure , running looped PDS was applied ; triclosan-coated or uncoated PDS was chosen by computer r and omization . Pre-operative and peri-operative variables such as gender , body mass index , neoadjuvant therapy , type II diabetes mellitus , amount of wound dressing material used , nursing days , and microbiological results were recorded . After the operation , the patient 's data and risk factors were collected in a password-protected online data base . RESULTS From 485 patients r and omized , SSI was documented in 47 patients ( 12.5 % ) , 23 ( 12.2 % ) in the group having triclosan-coated sutures ( n=188 ) and 24 ( 12.2 % ) in the uncoated suture group ( n=197 ) , a non-significant difference . Of all SSIs , 13 ( 27.7 % ) were diagnosed only after discharge , being recognized in the outpatient setting , with four patients in the triclosan suture group ( 8.5 % ) and nine in the uncoated suture group ( 19.2 % ) being affected with no significant differences in the demographic data . Microbiological examinations , in addition to the same colon flora in both groups , revealed two gram-positive infections in the uncoated suture group . The hospital stay and costs of dressings were significantly higher in patients having SSIs . CONCLUSION Compared with the previous retrospective studies of this department , the implementation of looped PDS decreased the incidence of SSI by one-half , whether the suture was triclosan-coated or not . It seems that patient factors are less important than operative factors in the occurrence of SSI , and there were no differences between elective colon and rectal operations in the development of incisional infections . No beneficial effect of triclosan against gram-positive bacteria , which has been reported in the literature , could be confirmed in our study . We could not show an effect against gram-negative enteric microorganisms . Higher additional costs and longer hospital stay with SSI were confirmed BACKGROUND Wound infections after abdominal surgery are still frequent types of nosocomial infections . Suture material s might serve as a vehicle for mechanical transport of bacteria into the surgical wound . To prevent the contamination of suture material in surgical wounds , triclosan-coated suture material s with antibacterial activity was developed . We here report a prospect i ve r and omized pathway controlled trial investigating the effect of triclosan impregnation of polydioxanone sutures used for abdominal wall closure on the rate of surgical-site infections . PATIENTS AND METHODS A total of 856 patients included in this trial underwent a st and ardized clinical pathway documented abdominal wall closure after abdominal surgery . Patients were r and omized to have the fascia closed with either a 2 - 0 polydioxanone loop or a triclosan impregnated 2 - 0 polydioxanone loop . The primary outcome was the number of wound infections . Risk factors for poor wound healing were collected prospect ively to compare the two groups . RESULTS When a PDS loop suture for abdominal wall closure was used , 42 ( 11.3 % ) patients with wound infections were detected . The number of patients with wound infections decreased significantly to 31 when the PDS plus for abdominal wall closure was used ( 6.4 % , P < .05 ) . Other risk factors for the development of side infections were comparably in the two groups . CONCLUSION This clinical pathway facilitated trial shows that triclosan impregnation of a 2 - 0 polydioxanone closing suture can decrease wound infections in patients having a laparotomy for general and abdominal vascular procedures BACKGROUND Surgical site infection is a common complication of surgery . Its morbidities range from delayed healing to systemic sepsis . It has impact on the economy and health care re sources . METHODS This study was a prospect i ve , r and omized , double-blinded , controlled multicenter study aim ed to compare triclosan-coated polyglactin 910 sutures with polyglactin 910 sutures for the reduction of surgical site infections . This article details the results from the Cairo University center . A total of 450 patients who had undergone different surgical procedures were enrolled ; 230 were enrolled in the study group and 220 were enrolled in the control group . RESULTS The study group and the control group were comparable regarding risk factors for surgical site infection . Surgical site infection incidence was 7 % in the study group and 15 % in the control group ( P = .011 ) . The mean extended stay as a result of infection was 3.71 days , with an average cost $ 91 US per day . CONCLUSIONS Use of the triclosan-coated polyglactin 910 antimicrobial suture lead to reduction of surgical site infection and has an impact on saving health care re sources . The triclosan-coated polyglactin 910 antimicrobial suture could save $ 1,517,727 yearly in this single center OBJECTIVE To report the results of a surveillance study on surgical site infections ( SSIs ) conducted by the International Nosocomial Infection Control Consortium ( INICC ) . DESIGN Cohort prospect i ve multinational multicenter surveillance study . SETTING Eighty-two hospitals of 66 cities in 30 countries ( Argentina , Brazil , Colombia , Cuba , Dominican Republic , Egypt , Greece , India , Kosovo , Lebanon , Lithuania , Macedonia , Malaysia , Mexico , Morocco , Pakistan , Panama , Peru , Philippines , Pol and , Salvador , Saudi Arabia , Serbia , Singapore , Slovakia , Sudan , Thail and , Turkey , Uruguay , and Vietnam ) from 4 continents ( America , Asia , Africa , and Europe ) . PATIENTS Patients undergoing surgical procedures ( SPs ) from January 2005 to December 2010 . METHODS Data were gathered and recorded from patients hospitalized in INICC member hospitals by using the methods and definitions of the Centers for Disease Control and Prevention National Healthcare Safety Network ( CDC-NHSN ) for SSI . SPs were classified into 31 types according to International Classification of Diseases , Ninth Revision , criteria . RESULTS We gathered data from 7,523 SSIs associated with 260,973 SPs . SSI rates were significantly higher for most SPs in INICC hospitals compared with CDC-NHSN data , including the rates of SSI after hip prosthesis ( 2.6 % vs. 1.3 % ; relative risk [ RR ] , 2.06 [ 95 % confidence interval ( CI ) , 1.8 - 2.4 ] ; P < .001 ) , coronary bypass with chest and donor incision ( 4.5 % vs. 2.9 % ; RR , 1.52 [ 95 % CI , 1.4 - 1.6 ] ; [ P < .001 ) ; abdominal hysterectomy ( 2.7 % vs. 1.6 % ; RR , 1.66 [ 95 % CI , 1.4 - 2.0 ] ; P < .001 ) ; exploratory abdominal surgery ( 4.1 % vs. 2.0 % ; RR , 2.05 [ 95 % CI , 1.6 - 2.6 ] ; P < .001 ) ; ventricular shunt , 12.9 % vs. 5.6 % ( RR , 2.3 [ 95 % CI , 1.9 - 2.6 ] ; P < .001 , and others . CONCLUSIONS SSI rates were higher for most SPs in INICC hospitals compared with CDC-NHSN data |
528 | 24,277,765 | This comprehensive analysis demonstrates that FMD of conduit arteries in humans is , at least in part , mediated by NO | Flow-mediated dilation ( FMD ) is a noninvasive index of endothelial function and vascular health in humans .
Studies examining the role of nitric oxide ( NO ) are not conclusive .
In this article , we quantified the contribution of NO in FMD of conduit arteries and explored the effect of the protocol ( ie , distal cuff , ≈5-minute ischemia ) and method of analysis ( ie , automated and continuous edge detection ) on the NO dependency of this test . | Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients . Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity OBJECTIVES The aim of this study was to examine the association between brachial artery flow-mediated dilation ( FMD ) and cardiovascular events in a cohort of initially asymptomatic post-menopausal women , with adjustment for the presence of the major cardiovascular risk factors . BACKGROUND Conventional major cardiovascular risk factors ( cigarette smoking , hypercholesterolemia , hypertension , and diabetes ) fail to explain nearly 50 % of cardiovascular events . Defining the magnitude of future risk for the development of clinical events is a major focus of effective primary prevention . Evaluation of endothelial function , utilizing the noninvasive measurement of the brachial artery FMD , may serve as a screening tool to individualize high-risk patients . METHODS We conducted a prospect i ve study on 2,264 post-menopausal women , age 54 + /- 6 years . The length of the follow-up was 45 + /- 13 months ( range 6 to 65 months ) . RESULTS During observation , 90 major events were recorded . Risk-adjusted relative risk values result ed 1.0 , 1.33 ( 95 % confidence interval [ CI ] 1.09 to 4.09 ) , and 4.42 ( 95 % CI 2.97 to 8.01 ) for women in the higher , intermediate , and lower tertile of FMD , respectively ( p < 0.0001 for trend ) . The event rate for women in the lower tertile ( FMD < or=4.5 % ) was greater than the combined event rate noted in the other 2 tertiles ( women in the lower tertile accounted for 51 events [ 56.6 % of total events ] ) . When added to age and other conventional cardiovascular risk factors ( smoking habits , presence of hypercholesterolemia , history of diabetes , hypertension ) , FMD contributed significantly to the model predicting cardiovascular events ( likelihood ratio chi-square change : 10.22 ; p < 0.0001 ) . CONCLUSIONS In post-menopausal women , the knowledge of FMD provided incremental prognostic information regarding the risk of developing cardiovascular events Abstract — Flow-mediated dilatation ( FMD ) of conduit arteries is dependent on an intact endothelium , although the mechanisms are not fully understood . Using high-resolution ultrasound , we examined the role of endothelial mediators in radial artery dilatation in response to transient ( short period of reactive hyperemia ) and sustained ( prolonged period of reactive hyperemia , h and warming , or an incremental infusion of acetylcholine into the distal radial artery ) hyperemia . After short episodes of reactive hyperemia , FMD was abolished by local infusion of the nitric oxide synthesis inhibitor NGmonomethyl-l-arginine ( 5.3±1.2 % versus 0.7±0.7 % , P < 0.001 ) . In contrast , basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia , h and warming , and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition . Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD . Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia , but the response to sustained hyperemia was normal . These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus . Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide , whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition . Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide – dependent pathway and preservation of non nitric oxide – mediated dilatation to sustained flow stimuli Studies of experimental diabetes mellitus ( DM ) suggest that increased nitric oxide ( NO ) bioactivity contributes to renal hyperfiltration . However , the role of NO in mediating hyperfiltration has not been fully eluci date d in humans . Our aim was to examine the effect of NO synthase inhibition on renal and peripheral vascular function in normotensive subjects with uncomplicated type 1 DM . Renal function and brachial artery flow-mediated vasodilatation ( FMD ) were measured before and after an intravenous infusion of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester ( l-NMMA ) in 21 healthy control and 37 type 1 DM patients . Measurements in DM participants were made under clamped euglycemic conditions . The effect of l-NMMA on circulating and urinary NO metabolites ( NO(x ) ) and cGMP and on urinary prostanoids was also determined . Baseline characteristics were similar in the two groups . For analysis , the DM patients were divided into those with hyperfiltration ( DM-H , n = 18 ) and normal glomerular filtration rate ( GFR ) levels ( DM-N , n = 19 ) . Baseline urine NO(x ) and cGMP were highest in DM-H. l-NMMA led to a decline in GFR in DM-H ( 152 ± 16 to 140 ± 11 ml·min(-1)·1.73 m(-2 ) ) but not DM-N or healthy control participants . The decline in effective renal plasma flow in response to l-NMMA ( 806 ± 112 to 539 ± 80 ml·min(-1)·1.73 m(-2 ) ) in DM-H was also exaggerated compared with the other groups ( repeated measures ANOVA , P < 0.05 ) , along with declines in urinary NO(x ) metabolites and cGMP . Baseline FMD was lowest in DM-H compared with the other groups and did not change in response to l-NMMA . l-NMMA reduced FMD and plasma markers of NO bioactivity in the healthy control and DM-N groups . In patients with uncomplicated type 1 DM , renal hyperfiltration is associated with increased NO bioactivity in the kidney and reduced NO bioactivity in the systemic circulation , suggesting a paradoxical state of high renal and low systemic vascular NO bioactivity Background — We sought to clarify , using functional and biological approaches , the role of epoxyeicosatrienoic acids , nitric oxide (NO)/reactive oxygen species balance , and endothelin-1 in conduit artery endothelial dysfunction during essential hypertension . Methods and Results — Radial artery diameter and mean wall shear stress were determined in 28 untreated patients with essential hypertension and 30 normotensive control subjects during endothelium-dependent flow-mediated dilatation induced by h and skin heating . The role of epoxyeicosatrienoic acids and NO was assessed with the brachial infusion of inhibitors of cytochrome P450 epoxygenases ( fluconazole ) and NO synthase ( NG-monomethyl-L-arginine [ L-NMMA ] ) . Compared with controls , hypertensive patients exhibited a decreased flow-mediated dilatation in response to postischemic hyperemia as well as to heating , as shown by the lesser slope of their diameter – shear stress relationship . In controls , heating-induced flow-mediated dilatation was reduced by fluconazole , L-NMMA , and , to a larger extent , by L-NMMA+fluconazole . In patients , flow-mediated dilatation was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole to a lesser extent than in controls . Furthermore , local plasma epoxyeicosatrienoic acids increased during heating in controls ( an effect diminished by fluconazole ) but not in patients . Plasma nitrite , an indicator of NO availability , increased during heating in controls ( an effect abolished by L-NMMA ) and , to a lesser extent , in patients , whereas , inversely , reactive oxygen species increased more in patients ( an effect diminished by L-NMMA ) . Plasma endothelin-1 decreased during heating in controls but not in patients . Conclusions — These results show that an impaired role of epoxyeicosatrienoic acids contributes , together with an alteration in NO/reactive oxygen species balance and endothelin-1 pathway , to conduit artery endothelial dysfunction in essential hypertension . Clinical Trial Registration — https://www.eudract.ema.europa.eu . Unique identifier : RCB2007-A001–10 - 53 BACKGROUND Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis . Therefore , we prospect ively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates . METHODS AND RESULTS Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine , sympathetic activation by cold pressor testing , dilator responses to increased blood flow , and dilation in response to nitroglycerin . Cardiovascular events ( cardiovascular death , unstable angina , myocardial infa rct ion , percutaneous transluminal coronary angioplasty , coronary bypass grafting , ischemic stroke , or peripheral artery revascularization ) served as outcome variables over a median follow-up period of 7.7 years . Patients suffering from cardiovascular events during follow-up ( n=16 ) had significantly increased vasoconstrictor responses to acetylcholine infusion ( P=0 . 009 ) and cold pressor testing ( P=0.002 ) , as well as significantly blunted vasodilator responses to increased blood flow ( P<0.001 ) and the intracoronary injection of nitroglycerin ( P=0.001 ) . Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis . By multivariate analysis , all tests of coronary vasoreactivity were significant , independent predictors of a poor prognosis , even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself . CONCLUSIONS Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates . Thus , the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease Design and participants A double-blind , crossover , r and omized study was design ed to evaluate the effect of 3-month treatment with a lower versus a higher antihypertensive dosage of ramipril ( 5 or 10 mg/day ) on nitric oxide (NO)-dependent vasodilation in 46 untreated patients with essential hypertension . Radial artery flow-mediated dilation ( FMD ) , before and after the intra-arterial infusion of NG-monomethyl-L-arginine ( L-NMMA ) , to block NO synthase , and the response to sublingual glyceril trinitrate ( GTN , 25 μg ) were measured at baseline and after the two treatment periods as a change in artery diameter ( computerized system from ultrasound scans ) . Plasma angiotensin II and oxidative stress markers were also assessed . Results FMD was significantly ( P < 0.01 ) lower in hypertensive patients ( 4.6 ± 1.8 % ) than in normotensive subjects ( 7.1 ± 2.6 % ) , whereas the response to GTN was similar . L-NMMA significantly ( P < 0.001 ) inhibited FMD in normotensive but not in hypertensive subjects . Mean 24-h ambulatory blood pressure , plasma angiotensin II and oxidative stress marker levels were similarly reduced at the end of the two treatment periods . Both dosages of ramipril significantly ( P < 0.001 ) increased FMD ( 5 mg : 5.9 ± 2.1 % ; 10 mg : 6.3 ± 2.4 % ) without modifying the response to GTN . However , compared with baseline ( 11 ± 19 % ) , the inhibiting effect of L-NMMA on FMD ( NO-dependent FMD ) was significantly ( P < 0.01 ) greater with ramipril 10 mg ( 49 ± 12 % ) than 5 mg per day ( 38 ± 15 % ) . The improvement in FMD and NO-dependent FMD was not related to changes in plasma levels of angiotensin II or markers of oxidative stress . Conclusion Treatment with ramipril at a higher dosage induced a greater improvement in NO-dependent vasodilation compared with the lower antihypertensive dosage in hypertensive patients Flow-mediated dilation of the brachial or radial artery in response to transient hyperaemic flow , the most widely used test of endothelial function , is only manifest after flow decays back to baseline . We examined whether this dissociation of flow and diameter might be explained by a reduction in transmural pressure generated by high flow . Studies were performed in healthy subjects 20 to 55 years of age . Flow-mediated dilation was measured in the radial artery using a st and ard protocol and after flow interruption at peak hyperemia during brachial artery infusion of saline and the NO synthase inhibitor NG-monomethyl-L-arginine ( 8 & mgr;mol/min ) . Flow interruption 20 seconds after cuff release ( during high flow but no dilatation ) produced an immediate increase in radial artery diameter of 5.36±2.12 % , inhibited by NG-monomethyl-L-arginine to 1.09±0.67 % ( n=8 ; P<0.001 ) . Mean intra-arterial radial blood pressure and , hence , transmural pressure fell after cuff release by a mean of 26±1.8 mm Hg ( n=6 ; P<0.0001 ) at the time of peak hyperemic flow . Modulation of transmural pressure within the brachial artery by cuff inflation around the artery demonstrated that this fall is sufficient to reduce arterial diameter by an amount similar to flow-mediated dilation . These results suggest that flow-dependent , NO-dependent dilation is offset by a flow-induced fall in local arterial pressure and , hence , in transmural pressure . Shear related NO release is likely to play a greater role in the short-term regulation of arterial tone than that suggested by flow-mediated dilation Background —Chronic heart failure ( CHF ) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due , in part , to elevated endothelin-1 plasma levels . In the present study , we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent , flow-mediated vasodilation ( FMD ) . Methods and Results —Twenty-one patients with CHF r and omly received either the endothelin A receptor blocker LU 135252 ( 30 mg/d , n=7 ; 300 mg/d , n=7 ) or a placebo ( n=7 ) . Using high-resolution ultrasound , FMD and endothelium-independent , nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF . FMD at baseline was impaired in all 21 patients with CHF ( 3.2±2 % ) when compared with the 11 controls ( 9.7±4.9%;P = 0.0005 ) . In comparison with baseline , FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it ( from 3.0±2.0 % to 4.9±2.9%;P = 0.04 ) , but FMD remained unchanged with placebo . Subgroup analysis , according to different dosages , revealed a significant increase of FMD compared with baseline ( from 2.4±1.5 % to 5.5±2.4%;P = 0.03 ) in the patients treated with the low-dose ( 30 mg/d ) , whereas a high dose of 300 mg/d failed to increase FMD significantly . Improvement in the high-dose group , however , may have been masked by reduced vasodilator capacity due to a significant increase in vessel size ( from 4.8±0.4 to 5.1±0.7 mm;P = 0.03 ) . Conclusions —These results suggest that endothelin A receptor blockade improves FMD in CHF patients Background —Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease ( CAD ) . We performed the first prospect i ve study evaluating whether early measurement of brachial artery endothelium-dependent dilation ( flow-mediated dilation [ FMD ] ) after coronary stenting could predict occurrence of in-stent-restenosis . Methods and Results —The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention ( PCI ) with stenting and at least 6 months of follow-up . All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI ; FMD was investigated before and after 5 minutes of occlusion of the brachial artery , and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates . Clinical in-stent restenosis was demonstrated in 20 patients ( 15 % ) , whereas 116 patients ( 85 % ) remained free of signs or symptoms of recurrent ischemia . FMD was significantly impaired in patients with restenosis versus those without restenosis ( percent diameter variation 4.6±5.8 % versus 9.5±6.6 % , P=0.002 ) ; moreover , 4 % of patients with FMD ≥7 % ( median value ) developed in-stent restenosis versus 28 % of those with FMD < 7 % ( P=0.0001 ) . On multivariate analysis , FMD was the strongest predictor of restenosis ( OR 4.5 , 95 % CI 2.4 to 12.0 ) ; conversely , nitroglycerin-mediated dilation did not independently predict the risk of restenosis ( OR 2.4 , 95 % CI 0.8 to 6.3 ) . Conclusions —This is the first prospect i ve study indicating that impaired FMD independently predicts occurrence of in-stent restenosis in patients undergoing PCI . Early evaluation of endothelial function after stenting may represent a useful screening tool to stratify patients according to future risk of restenosis Objective —Endothelial dysfunction is an early event in the natural progression of heart failure . Increased oxidative stress has been linked to impaired endothelial function and both may play a prognostic role . Methods and Results —Endothelium-dependent and endothelium-independent vasodilatation were determined in 289 patients with mild left ventricular dysfunction by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . Vascular effects of the coadministration of the antioxidant vitamin C at pharmacological doses ( 24 mg/min ) were assessed . Occurrence of death , heart transplantation , and readmission with worsening heart failure were recorded as clinical outcome parameters during a follow-up period of 4.8 years . Patients experiencing adverse events ( n=79 ) had lower vasodilator responses to acetylcholine ( P<0.001 ) and to sodium nitroprusside ( P=0.03 ) compared with patients without events . However , beneficial effects of vitamin C did not differ between both groups . Cox proportional hazards model demonstrated that age ( P=0.001 ) , renal function ( P=0.001 ) , and blunted acetylcholine-induced vasodilatation ( P=0.007 ) remained independent predictors of adverse outcome . Conclusions —Impaired peripheral endothelial function independently predicts long-term adverse outcome in patients with early-stage heart failure . The findings suggest that assessment of peripheral endothelial function may represent an additional mean for risk stratification and therapy management in these patients OBJECTIVES This study was design ed to assess the effect of flavanol-rich food on the circulating pool of bioactive nitric oxide ( NO ) and endothelial dysfunction in smokers . BACKGROUND Studies suggest that smoking-related vascular disease is caused by impaired NO synthesis and that diets rich in flavanols can increase bioactive NO in plasma . METHODS In smokers ( n = 11 ) , the effects of flavanol-rich cocoa on circulating NO species in plasma ( RXNO ) measured by reductive gas-phase chemiluminescence and endothelial function as assessed by flow-mediated dilation ( FMD ) were characterized in a dose-finding study orally administering cocoa containing 88 to 370 mg flavanols and in a r and omized double-blind crossover study using 100 ml cocoa drink with high ( 176 to 185 mg ) or low ( < 11 mg ) flavanol content on two separate days . In addition to cocoa drink , ascorbic acid and NO-synthase inhibitor L-NMMA ( n = 4 ) were applied . RESULTS There were significant increases in RXNO ( 21 + /- 3 nmol/l to 29 + /- 5 nmol/l ) and FMD ( 4.5 + /- 0.8 % to 6.9 + /- 0.9 % , each p < 0.05 ) at 2 h after ingestion of 176 to 185 mg flavanols , a dose potentially exerting maximal effects . These changes correlated with increases in flavanol metabolites . Cocoa-associated increases in RXNO and FMD were reversed by L-NMMA . Ascorbic acid had no effect . CONCLUSIONS The circulating pool of bioactive NO and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink . The increase in circulating NO pool may contribute to beneficial vascular health effects of flavanol-rich food Whether AT(1 ) ( angiotenin II type 1 ) receptor blockade can prevent the decrease in conduit artery FMD ( flow-mediated dilatation ) during NOS ( nitric oxide synthase ) inhibition by alternative endothelial pathways has not been explored previously in humans . In 12 healthy subjects , we measured radial artery diameter ( echotracking ) and flow ( Doppler ) during FMD induced by sustained reactive hyperaemia during a control period and following NOS inhibition [ 1.5 mg.min(-1).l(-1 ) L-NMMA ( N(G)-monomethyl-L-arginine ) ] , after a single oral administration of telmisartan ( 80 mg ) or placebo , using a r and omized double-blind cross-over design . In six volunteers , we also assessed the roles of prostacyclin and EDHF ( endothelium-derived hyperpolarizing factor ) during radial FMD after AT(1 ) receptor blockade by oral administration of aspirin ( 500 mg ) alone , aspirin+L-NMMA or aspirin+L-NMMA+fluconazole ( a cytochrome epoxygenases inhibitor ; 0.37 mg.min(-1).l(-1 ) ) . Telmisartan did not affect radial artery FMD in the control period ( 10.9+/-0.6 % with placebo compared with 9.9+/-0.7 % with telmisartan ) , but prevented its decrease after L-NMMA ( 9.3+/-0.8 % with placebo compared with 12.6+/-1.2 % with telmisartan ; P<0.05 ) with no modification in baseline parameters , hyperaemia and radial artery endothelium-independent dilatation to sodium nitroprusside . Moreover , in telmisartan-treated subjects , radial artery FMD , compared with control ( 9.0+/-1.0 % ) , was not modified by aspirin alone ( 9.4+/-0.7 % ) or associated with L-NMMA ( 9.5+/-0.5 % ) , but was reduced by the combination of aspirin , L-NMMA and fluconazole ( 7.5+/-0.6 % ; P<0.05 ) . These results demonstrate that AT(1 ) receptor blockade prevents the decrease in conduit artery FMD during NOS inhibition in humans , suggesting the development of a compensatory endothelial mechanism . This mechanism appears to be independent of prostacyclin and could possibly be related to an EDHF release 1 The role of the balance between nitric oxide ( NO ) and endothelium‐derived hyperpolarizing factor ( EDHF ) , synthesized by cytochrome epoxygenase and acting through calcium‐activated potassium channels , in the regulation of basal diameter and endothelium‐dependent flow‐mediated dilatation of conduit arteries has been poorly assessed in humans . 2 Radial artery diameter and flow ( echotracking coupled to Doppler ) were measured in healthy volunteers under basal conditions and during flow‐mediated dilatation induced by h and skin heating , in the presence of saline and inhibitors of NO‐synthase , NG‐monomethyl‐L‐arginine ( L‐NMMA ) , calcium‐activated potassium channels , tetraethylammonium ( TEA ) and cytochrome epoxygenases , fluconazole , infused alone and in combination . Mean wall shear stress , the flow‐mediated dilatation stimulus , was calculated and taken as cofactor into statistical analysis . 3 Under basal conditions , the radial artery diameter was not affected by L‐NMMA and fluconazole infused alone but was decreased by TEA , the combinations of L‐NMMA + fluconazole and , to a greater extent , L‐NMMA + TEA . During heating , radial artery diameter increased with temperature in all cases . This increase in diameter , compared with saline , was reduced by L‐NMMA , TEA , fluconazole and to a greater extent , by L‐NMMA + TEA and L‐NMMA + fluconazole . 4 These data show that EDHF is involved in balance with NO in the regulation of basal diameter and endothelium‐dependent dilatation of human peripheral conduit arteries . The alteration of this balance could play a major role in the physiopathology of the endothelial dysfunction , in particular during essential hypertension The objective of this study was to determine whether abnormal flow-induced endothelium-dependent vasodilation in the brachial artery identifies young patients with coronary artery disease ( CAD ) . High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel , the brachial artery , in 14 young men with CAD and in 11 age-matched , healthy , male volunteers . Endothelium-dependent vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia . Endothelium-independent vasodilation was assessed by administration of sublingual nitroglycerin . To ascertain whether flow-mediated vasodilation in humans is mediated by endothelium-derived nitric oxide , brachial artery diameter was measured during reactive hyperemia , before and during administration of the nitric oxide synthase antagonist NG-monomethyl-L-arginine ( L-NMMA ) . Brachial artery diameter was also measured during intraarterial infusion of acetylcholine and nitroprusside before and after administration of L-NMMA . Flow-induced vasodilation was less in patients with CAD than in healthy volunteers ( 1.3 + /- 1.1 % vs 6.2 + /- 0.7 % , p < 0.05 ) . Nitroglycerin increased brachial artery diameter similarly in each subject group ( 11.3 + /- 1.0 % vs 15.8 + /- 1.2 % , p = 0.05 ) . L-NMMA inhibited flow-mediated vasodilation and the vasodilative response to acetylcholine , but did not affect the response to nitroprusside . It is concluded that abnormal flow-induced endothelium-dependent vasodilation occurs in the brachial artery of young patients with CAD As a stressful lifestyle has been associated with coronary heart disease , this study aim to evaluate how two stressful tests influence endothelial-dependent vasodilation evaluated by flow-mediated dilation ( FMD ) of the brachial artery . FMD following 5 min of occlusion of the forearm was evaluated in young healthy volunteers with measurements of brachial artery diameter and blood flow ( BABF ) using ultrasound before and during a mental arithmetic task ( MAT ) , and during cold pressure test ( COP ) . MAT and COP increased blood pressure to a similar degree ( 18 - 21 mmHg ) . The COP induced a significant reduction in FMD compared to the baseline levels ( from 9.3 - 3.9 to 5.9 - 3.2 % , p < 0.01 ) , as well as to the MAT , which in itself did not influence FMD ( 10.1 - 5.0 % ) . However , as MAT increased BABF during hyperaemia significantly , the FMD to BABF ratio was significantly reduced by both stress tests ( p < 0.05 ) . Time-control experiments showed FMD measurements to be reproducible and that MAT and COP by themselves only marginally affected brachial artery diameter . In conclusion , cold pressure stress induced an impairment in FMD , but no effect was induced by a MAT . However , when FMD was normalized for the degree of hyperaemic blood flow , the driver of the vasodilation in the brachial artery , a reduction in flow-mediated vasodilation was seen during both mental and cold pressure stress Forearm vascular responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators have been thoroughly characterized in humans . While the forearm is a well-established experimental model for study ing human vascular function , it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements . In the present study we determined whether these responses could be generalized to the leg . Based upon blood pressure differences between the leg and arm during upright posture , we hypothesized that the responsiveness to endothelium-dependent vasodilators would be greater in the forearm than the leg . Brachial and femoral artery blood flow ( Q , ultrasound Doppler ) at rest and during intra-arterial infusions of endothelium-dependent ( acetylcholine and substance P ) and -independent ( sodium nitroprusside ) vasodilators were measured in eight healthy men ( 22 - 27 years old ) . Resting blood flows in the forearm before infusion of acetylcholine , substance P or sodium nitroprusside were 25 + /- 4 , 30 + /- 7 and 29 + /- 5 ml min(-1 ) , respectively , and in the leg were 370 + /- 32 , 409 + /- 62 and 330 + /- 30 ml min(-1 ) , respectively . At the highest infusion rate of acetylcholine ( 16 microg ( 100 ml tissue)(-1 ) min(-1 ) ) there was a greater ( P < 0.05 ) increase in Q to the forearm ( 1864 + /- 476 % ) than to the leg ( 569 + /- 86 % ) . Similarly , at the highest infusion rate of substance P ( 125 pg ( 100 ml tissue)(-1 ) min(-1 ) ) there was a greater ( P < 0.05 ) increase in Q to the forearm ( 911 + /- 286 % ) than to the leg ( 243 + /- 58 % ) . The responses to sodium nitroprusside ( 1 microg ( 100 ml tissue)(-1 ) min(-1 ) ) were also greater ( P < 0.05 ) in the forearm ( 925 + /- 164 % ) than in the leg ( 326 + /- 65 % ) . These data indicate that vascular responses to both endothelium-dependent and -independent vasodilator agents are blunted in the leg compared to the forearm |
529 | 19,118,414 | Conclusions In the current literature , no firm consensus exists on the importance of haptic feedback in performing minimally invasive surgery .
Benefits are least disputed when related to surgery using robotics , because there is no haptic feedback in currently used robotics .
The addition of haptics is believed to reduce surgical errors result ing from a lack of it , especially in knot tying .
Concerning VR training , results indicate that haptic feedback is important during the early phase of psychomotor skill acquisition | Background Virtual reality ( VR ) as surgical training tool has become a state-of-the-art technique in training and teaching skills for minimally invasive surgery ( MIS ) .
Although intuitively appealing , the true benefits of haptic ( VR training ) platforms are unknown .
Many questions about haptic feedback in the different areas of surgical skills ( training ) need to be answered before adding costly haptic feedback in VR simulation for MIS training .
This study was design ed to review the current status and value of haptic feedback in conventional and robot-assisted MIS and training by using virtual reality simulation . | Background A variety of minimally invasive parathyroidectomy ( MIP ) techniques have been currently introduced to surgical management of primary hyperparathyroidism ( pHPT ) caused by a solitary parathyroid adenoma . This study aim ed at comparing the video-assisted MIP ( MIVAP ) and open MIP ( OMIP ) in a prospect i ve , r and omized , blinded trial . Material s and Methods Among 84 consecutive pHPT patients referred for surgery , 60 individuals with concordant localization of parathyroid adenoma on ultrasound and subtraction Tc99m-MIBI scintigraphy were found eligible for MIP under general anesthesia and were r and omized to two groups ( n = 30 each ) : MIVAP and OMIP . An intraoperative intact parathyroid hormone ( iPTH ) assay was routinely used in both groups to determine the cure . Primary end-points were the success rate in achieving the cure from hyperparathyroid state and hypocalcemia rate . Secondary end-points were operating time , scar length , pain intensity assessed by the visual-analogue scale , analgesia request rate , analgesic consumption , quality of life within 7 postoperative days ( SF-36 ) , cosmetic satisfaction , duration of postoperative hospitalization , and cost-effectiveness analysis . Results All patients were cured . In 2 patients , an intraoperative iPTH assay revealed a need for further exploration : in one MIVAP patient , subtotal parathyroidectomy for parathyroid hyperplasia was performed with the video-assisted approach , and in an OMIP patient , the approach was converted to unilateral neck exploration with the final diagnosis of double adenoma . MIVAP versus OMIP patients were characterized by similar operative time ( 44.2 ± 18.9 vs. 49.7 ± 15.9 minutes ; P = 0.22 ) , transient hypocalcemia rate ( 3 vs. 3 individuals ; P = 1.0 ) , lower pain intensity at 4 , 8 , 12 , and 24 hours after surgery ( 24.9 ± 6.1 vs. 32.2 ± 4.6 ; 26.4 ± 4.5 vs. 32.0 ± 4.0 ; 19.6 ± 4.9 vs. 25.4 ± 3.8 ; 15.5 ± 5.5 vs. 20.4 ± 4.7 points , respectively ; P < 0.001 ) , lower analgesia request rate ( 63.3 % vs. 90 % ; P = 0.01 ) , lower analgesic consumption ( 51.6 ± 46.4 mg vs. 121.6 ± 50.3 mg of ketoprofen ; P < 0.001 ) , better physical functioning aspect and bodily pain aspect of the quality of life on early recovery ( 88.4 ± 6.9 vs. 84.6 ± 4.7 and 90.3 ± 4.7 vs. 87.5 ± 5.8 ; P = 0.02 and P = 0.003 , respectively ) , shorter scar length ( 17.2 ± 2.2 mm vs. 30.8 ± 4.0 mm ; P < 0.001 ) , and higher cosmetic satisfaction rate at 1 month after surgery ( 85.4 ± 12.4 % vs. 77.4 ± 9.7 % ; P = 0.006 ) . Cosmetic satisfaction was increasing with time , and there were no significant differences at 6 months postoperatively . MIVAP was more expensive ( US$ 1,150 ± 63.4 vs. 1,015 ± 61.8 ; P < 0.001 ) while the mean hospital stay was similar ( 28 ± 10.1 vs. 31.1 ± 9.7 hours ; P = 0.22 ) . Differences in serum calcium values and iPTH during 6 months of follow-up were nonsignificant . Transient laryngeal nerve palsy appeared in one OMIP patient ( P = 0.31 ) . There was no other morbidity or mortality . Conclusions Both MIVAP and OMIP offer a valuable approach for solitary parathyroid adenoma with a similar excellent success rate and a minimal morbidity rate . Routine use of the intraoperative iPTH assay is essential in both approaches to avoid surgical failures of overlooked multigl and ular disease . The advantages of MIVAP include easier recognition of recurrent laryngeal nerve ( RLN ) , lower pain intensity within 24 hours following surgery , lower analgesia request rate , lower analgesic consumption , shorter scar length , better physical functioning and bodily pain aspects of the quality of life on early recovery , and higher early cosmetic satisfaction rate . However , these advantages are achieved at higher costs because of endoscopic tool involvement BACKGROUND AND PURPOSE Robotic surgery allows three-dimensional ( 3D ) viewing of tissues . We compared two-dimensional ( 2D ) and 3D suturing drills using the daVinci surgical system to determine if the latter is advantageous . MATERIAL S AND METHODS Twenty-eight anastomotic drills were completed by seven surgeons using the daVinci robot . Three surgeons had considerable ( > 6 months ) robotic experience , and four had none . Drills were performed r and omly in both dimensional modes in a blinded fashion . Drill 1 was an interrupted four stitch and drill 2 a running closure . All tasks were kept uniform . We recorded time to completion , difficulty , and accuracy . The drills were evaluated by two independent review ers for accuracy and major errors ( i.e. , broken suture , torn graft ) . RESULTS The average operative time per drill in two dimensions was 13.1 minutes ( range 6.9 - 21.9 minutes ) and in three dimensions was 8.5 minutes ( range 4.7 - 12.8 minutes ) ( P<0.001 ) . Drill 1 was 6.1 minutes faster in three dimensions ( mean 9.2 minutes ; P<0.01 ) , and drill 2 was 2.9 minutes faster ( mean 7.8 minutes ; P=0.03 ) . Both advanced and novice groups were faster in 3D ( P<0.01 ) . There were two major errors in the 3D performances and 5 in the 2D exercises ( P<0.05 ) . The participants correctly identified the dimensional mode 92.9 % of the time ( P<0.01 ) . CONCLUSION The anastomosis was completed 65 % faster using 3D with equal , if not greater , accuracy . Drill 1 was improved to a greater degree than drill 2 , suggesting most benefit of 3D views during knot tying . Use of three dimensions outperformed two dimensions in both groups . Surgeons can immediately benefit from 3D viewing during robotic surgery Background and aims Laparoscopic surgery has become the treatment of choice for cholecystectomy . Many studies showed that while this approach benefits the patient , the surgeon faces such distinct disadvantages as a poor ergonomic situation and limited degrees of freedom with limited motion as a consequence . Robots have the potential to overcome these problems . To evaluate the efficiency and feasibility of robotically assisted surgery ( RAC ) , we design ed a prospect i ve study to compare it with st and ard laparoscopic cholecystectomy ( SLC ) . Material s and methods Between 2001 and 2003 , 26 patients underwent SLC and 20 patients underwent RAC using the ZEUS system . The feasibility , safety , and possible advantages were evaluated . To assess the efficacy , the total time in the operating room was divided into preoperative , operative , and postoperative time frames . Results For RAC in comparison with SLC , the preoperative phase including equipment setup was significantly longer . In the intraoperative phase , the cut-closure time and camera and trocar insertion times were significantly longer . It is interesting to note that the net dissection time for the cystic artery , duct , and the gall bladder was not different from SLC . Conclusions The study demonstrates the feasibility of robotically assisted cholecystectomy without system-specific morbidity . There is time loss in several phases of robotic surgery due to equipment setup and deinstallation and therefore , presents no benefit in using the robot in laparoscopic cholecystectomy Robotic laparoscopic surgery is postulated to result in better surgical results by allowing improved instrument manipulation and three-dimensional vision . The authors ’ experience performing robot-assisted laparoscopic colorectal surgery is reported . METHOD : St and ard laparoscopic procedures with robot-assisted laparoscopic colon mobilization and vascular ligation were performed . Data relating to the operative procedure , hospital stay , and direct costs were collected . Results were compared with age , gender , and procedure case-matched controls taken from a prospect i ve laparoscopic colorectal surgery data base . RESULTS : Six robot-assisted laparoscopic surgeries ( 2 right hemicolectomies , 3 sigmoid colectomies , and 1 Wells rectopexy ) were performed between December 2001 and June 2002 . There was no associated morbidity . Operative time was increased from a median time of 108 minutes for st and ard laparoscopic colorectal surgery to 165 minutes for robot-assisted laparoscopic surgeries ( P = 0.0313 ; Wilcoxon matched-pairs signed-rank test for non-parametric data ) . This was primarily a result of the time required for robot set-up . Blood loss , length of stay , and hospital cost were not significantly different between groups . Additional direct equipment costs for RAC cases included robotic laparoscopic instruments and sterile drapes ( approximately US $ 350 per case ) , without including acquisition and maintenance costs for the robot . CONCLUSION : Robot-assisted laparoscopic colectomy is a feasible and safe procedure . Although three-dimensional vision and dexterity are facilitated , operative time is increased and the overall additional expense of robotics is of concern . Robot-assisted laparoscopic colectomy requires further evaluation to establish clinical and financial benefits before introduction to routine practice . Such techniques may , in the future , facilitate complex laparoscopic techniques Background This study aim ed to investigate the effect of a virtual reality simulator on the learning of basic robotic suturing skills . Methods Two r and omized groups of students underwent a controlled training program . Both groups completed an identical test before and after training . The increase in the number of stitches placed during the pretest and posttest was used as an objective measure of the training effect . To evaluate the subjective feeling of underst and ing and mastering , the students indicated this on a visual analog scale . Results Both groups showed a significant increase in the number of stitches placed during the posttest , and an increase in subjective feeling of underst and ing and mastering . The increase did not differ between the groups , indicating that the virtual reality simulator equaled the mechanical trainer in training of robotic suturing technique . Conclusions Training in basic robot-assisted suturing skills using a virtual reality simulator without additional training equaled training using a mechanical simulator Objective : This study aim ed to compare the outcomes of laparoscopic resection ( LR ) with open resection ( OR ) for right-sided colon cancer . Methods : During the study period from June 2000 to December 2004 , 182 patients ( 84 men ) underwent elective resection for cancer of the right colon . Laparoscopic resection was performed in 77 patients , while 105 patients had open operations . Patients who underwent operations on an emergency basis were excluded . Data on the patients ' demographics , operative details , and postoperative complications were collected prospect ively . The outcomes of patients with laparoscopic resection were compared with those of patients with open surgery . Results : There was no difference in the age , sex , presence of premorbid medical conditions , and blood loss between the 2 groups . The mean operative time for open resection was 115.4 minutes and that for laparoscopic resection was 165.1 minutes ( P<0.001 ) . Among the 77 patients who underwent laparoscopic resection , 7 ( 9 % ) required conversion to an open operation . There was no difference in postoperative surgically related complications including wound infection , leakage , intestinal obstruction , postoperative ileus . Nonsurgical-related complications were also similar . The median time to resumption of a normal diet was 3 days and 4 days in the laparoscopic and open groups , respectively . The median hospital stay in patients with laparoscopic resection was significantly shorter than in patients with open surgery ( 6.0 days vs 7.0 days , P<0.001 ) . The 2-year overall survival rates were 74 % in both groups ( P=0.904 ) . In the converted to open ( LCOR ) group , the hospital stay was significantly longer ( LR vs OR vs LCOR , 5.5 days vs 7.0 days vs 9.0 days respectively , P<0.001 ) . Conclusion : Laparoscopic right hemicolectomy is a safe option for cancers of the right colon . It is associated with a shorter hospital stay and earlier resumption of a normal diet . Mortality and morbidity are similar to that with the open approach . There is no compromise in the survival of patients This study examined the impact of virtual reality ( VR ) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy BACKGROUND It is not clear if robotically assisted surgery ( providing articulating instruments , 3-dimensional vision , intuitive ergonomics ) performed in pediatric patients offers the same advantages over conventional surgery as in adult patients . In the laboratory setting , robots require less time to perform certain tasks . Accordingly , we tested the hypothesis that the time required to perform a robotically assisted laparoscopic Thal semifundoplication is different compared with a conventional laparoscopic procedure in children . METHODS The time required to perform single operative steps was prospect ively recorded in 10 consecutively performed Thal semifundoplications with the use of a robot ( da Vinci ) and in 10 consecutively performed operations done by conventional laparoscopy . RESULTS No conversion to an open operation was necessary , and there were no intraoperative complications throughout the study and no postoperative complications up to 14 months after surgery . Total operative time was similar in both groups . In the robotically assisted group , time for setup was significantly longer ( 20.8 + /- 7.5 vs 34.6 + /- 9.2 minutes , P < .05 ) , but dissection of the hiatal region as the most challenging operative step was accomplished 34 % faster in the robotically assisted group ( 30.8 + /- 8.7 vs 20.2 + /- 5.3 minutes , P < .05 ) . CONCLUSION At the current level of technology , the robotic system is superior compared with established st and ard laparoscopic techniques requiring tissue preparation ; however , the potential benefit in operating time is counterbalanced by the increased complexity of setting up the system Background : This study was undertaken to investigate operating room performance of surgical residents , after participating in the Eindhoven virtual reality laparoscopic cholecystectomy training course . This course is the first formal surgical resident trainings course , using a variety of complementary virtual reality ( VR ) skills training simulation in order to prepare surgical residents for their first laparoscopic cholecystectomy . The course was granted EAES certification . Methods : The four-day course is based on multimedia and multimodality approach . A variety of increasingly difficult simulation training sessions , next to intimate focus-group “ knowledge sessions ” are included . Both basic and procedural VR simulation is featured , using MIST-VR and the Xitacts ' LapChol simulation software . The operating room performance of twelve surgical residents who participated in the course and twelve case-control counterparts were compared . The case-control grup was matched for clinical number laparoscopic cholecystectomy performance ( maximum of 4 procedures ) . Two observers analyzed a r and omly mixed videotape , featuring the part of the “ clip- and -cut ” procedure of the laparoscopic cholecystectomy , and were blinded for participants ' group status . Structured question naires including multiple observation scales were used to assess performance . Results : Residents of both the experimental and control group did not differ in demographic parameters , except for number of laparoscopic cholecystectomies in favor of the control group ( p-value 0.008 ) . Both observers judge the experimental group to perform significantly better ( p-value 0.004 and 0.013 ) . Experimental group residents valued their course highly in terms of their laparoscopic surgical skills improvement and the use of VR simulators in the surgical curiculum . Conclusions : The Eindhoven Virtual Reality laparoscopic cholecyctectomy training course improves surgical skill in the operating room above the level of residents trained by a variety of other training methods Background Not much is known about the exact role of force feedback in laparoscopy . This study aim ed to determine whether force feedback influences movements of instruments during training in laparoscopic tasks and whether force feedback is required for training in basic laparoscopic force application tasks . Methods A group of 19 gynecologic residents , r and omly divided into two groups , performed three laparoscopic tasks in both the box trainer and the virtual reality ( VR ) trainer . The box-VR group began with the box trainer , whereas the VR-box group began with the VR trainer . The three selected tasks included different levels of force application . The box trainer provides natural force feedback , whereas the VR trainer does not provide force feedback . The performance of the two groups was compared with regard to time , path length , and depth perception . Results For the tasks in which force plays hardly a role , no differences between box-VR group and the VR-box group were found . During a task in which force application ( pulling and pushing forces ) plays a role , the box-VR group outperformed VR-box group in the box trainer . Moreover , training with the box trainer had a positive effect on subsequent performance of the task with the VR trainer . This was not found the other way around . No differences were found between box-VR and the VR-box group in tasks not requiring force application . Conclusion Force feedback influences basic laparoscopic skills during tasks in which pulling and pushing forces are applied . For these tasks , the switch from the trainer without force feedback to the one with natural force feedback has a detrimental effect on performance . Therefore , training for tasks in which forces play an important role ( e.g. , stretching , grasping ) should be done using systems with natural force feedback , whereas eye – h and coordination can be trained without force feedback Background A new technical tool was developed and introduced into the therapeutic field of videoscopic surgery — robotic telemanipulation surgery . The aim of this study is to investigate in a prospect i ve r and omized trial the feasibility of the Nissen procedure using the da Vinci and to evaluate the benefits and the costs of this new technique compared with the conventional laparoscopic approach . Material s and methods Twenty patients with gastro-esophageal reflux disease ( GERD ) were r and omized into laparoscopic Nissen versus robot-assisted Nissen fundoplication . All the patients signed an informed consent document . The time data of the procedure , the efficacy of the instruments , the intra-operative incidents , postoperative morbidity , and cost minimization are presented . Results Nine patients were assigned to the robot , and 11 to the laparoscopic procedure . Both groups were similar in age , male/female ratio , and body mass index . The robot procedure time was significantly longer . The hospital stay and the alimentation day were similar . The number of postoperative complaints was similar after the 1st , 6th , and 12th postoperative months . However , on the 3rd postoperative month , the number of complaints was significantly higher in the robot group . The robot procedure was more expensive with regard to the instrumentation and reusable material , the nursing costs , the investment costs , and the maintenance costs . Conclusions No clear advantage of using robotics in the Nissen procedure was observed . The procedure seems to be feasible and safe . The technique is limited because of unadapted instruments . The disadvantages are the high costs and prolonged operative time Background Laparoscopic Roux-en-Y gastric bypass surgery ( RYGB ) was introduced at the authors ’ institution 5 years ago . The authors analyzed the short- and long-term results of this procedure compared with those for the same procedure using the laparotomy approach over the same period . Methods Retrospective analysis of a prospect ively collected bariatric data base used the outcome end points used by the American Society of Bariatric Surgery ( ASBS ) and the American College of Surgeons ( ACS ) in their center of excellence programs . Results From January 2001 to July 2005 , 568 laparoscopic and 399 open gastric bypasses were performed at V and erbilt University . The patients were from the same bariatric surgery program and therefore received the same pre- and postoperative care . The hospital length of stay in the laparoscopic group was significantly shorter ( 2.5 ± 2.4 days ) than in the open group ( 3.7 ± 3.7 days ; p = 0.001 ) . The procedure time was significantly shorter in the laparoscopic group ( 164 ± 50 min ) than in the open group ( 195 ± 50 min ; p = 0.0001 ) . The follow-up assessment response at 2 years was 76.6 % . At 2 years , the excess weight loss ( EWL ) was significantly greater in the laparoscopic group ( 71.3 % ± 18.4 % ) than in the open group ( 67.3 % ± 15.3 % ; p = 0.03 ) . The wound infection rate was significantly higher in open group ( 9.2 % ) than in the laparoscopic group ( 1.7 % ; p = 0.001 ) . There was no significant difference in 30-day mortality : open ( 0.50 % ) versus laparoscopic ( 0.17 % ; p = 0.371 ) . There was no significant difference in the 30-day reoperation rate between the open ( 2.4 % ) and laparoscopic ( 2.6 % ; p = 0.705 ) groups . The 30-day readmission rate was similar in the open ( 5.0 % ) and laparoscopic ( 5.2 % ; p = 0.852 ) groups , as was the rate of leakage from the gastrojejunostomy in the open ( 0.50 % ) and laparoscopic ( 0.35 % ; p = 0.127 ) groups . The conversion rate from laparoscopic procedure to laparotomy was 1.7 % . Conclusion In the authors ’ institution , a laparoscopic bariatric surgery program with a very low rate of morbidity and mortality has been introduced . Operative time , hospital stay , and wound complications are reduced with the laparoscopic approach . The laparoscopic and open procedures are equally safe , with equivalent 30-day mortality , readmission , reoperation , and gastrojejunostomy leakage rates INTRODUCTION The applications of Minimally Invasive Surgery ( MIS ) and Laparoscopy are rapidly exp and ing . Despite this expansion , the technology related to our underst and ing of the importance of haptic feedback related to laparoscopic surgery remains in its infancy . While many surgeons feel that the use of minimally invasive techniques eliminates force feedback and tactile sensation , the importance of haptics in MIS has not been fully evaluated . Moreover , there is considerable interest in the development of haptic simulators for MIS even though the importance of force feedback remains poorly understood . This study was design ed to determine the ability of novice surgeons to interpret haptic feedback with respect to texture , shape and consistency of an object . METHOD Subjects were presented objects in a r and om order and participants were blinded as to their identity . Inspection by direct palpation , palpation with conventional instruments , and palpation with laparoscopic instruments was performed on all objects . Statistical analysis of the data was performed using a Fischer exact probability test . RESULTS Direct palpation provided the greatest degree of haptic feedback and was associated with the highest accuracy for texture discrimination , shape discrimination , and consistency discrimination . A significant decrease in the ability to identify shapes was noted with both CI and LI . A significant decrease in the ability to differentiate consistency was noted for LI only . When comparing palpation with conventional instruments to palpation with laparoscopic instruments , there was no significant difference in shape or texture discrimination . There was , however , a significant decrease in consistency discrimination . CONCLUSION This data indicates that laparoscopic instruments do in fact provide the surgeon with haptic feedback . While the instruments change the information available to the surgeon , interpretation of the texture , shape and consistency of objects can be performed . Our ongoing work is directed at further defining force interactions . Through the use of force feedback impulse devices in VR simulators , one should be able to create a more realistic theatre in which the novice surgeon can learn operative skills that will readily translate into the operating room Purpose This study was design ed to compare laparoscopic vs. open total mesorectal excision for cancer of the rectum on perioperative outcome and quality of life . Methods A total of 187 consecutive unselected patients with rectal cancer who underwent total mesorectal excision during a seven-year period were prospect ively evaluated . Patients were monitored 30 days for postoperative complications . Quality of life was evaluated before and at one year after surgery . Results A total of 108 patients underwent laparoscopic total mesorectal excision , whereas 79 underwent open . Conversion rate was 12 percent . In the laparoscopic group , operating time was 33 minutes longer ( P = 0.03 ) and intraoperative blood loss was lower ( P = 0.001 ) . Tumor stage and the number of lymph nodes that were intraoperatively collected were similar in the two groups . The overall morbidity rate was 29.6 percent in the laparoscopic and 27.8 percent in the open ( P = 0.78 ) group . No patient died during the postoperative period . Anastomotic leak rate was similar in the two groups ( 14.8 percent in laparoscopic vs. 12.6 percent in open ; P = 0.88 ) . Patients in the laparoscopic group recovered earlier bowel function ( P = 0.01 ) and experienced a shorter length of stay ( P = 0.003 ) . At one-year follow-up , overall quality of life was similar in the two groups . In the laparoscopic group , social functioning item was significantly better ( P = 0.05 ) and trend to a better physical status was observed ( P = 0.07 ) . Conclusions Laparoscopic total mesorectal excision is safe and feasible , does not jeopardize the complication rate , and has the benefits of much less blood during the operation and shorter hospitalization Objective To demonstrate that virtual reality ( VR ) training transfers technical skills to the operating room ( OR ) environment . Summary Background Data The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospect i ve , r and omized , blinded study . Methods Sixteen surgical residents ( PGY 1–4 ) had baseline psychomotor abilities assessed , then were r and omized to either VR training ( MIST VR simulator diathermy task ) until expert criterion levels established by experienced laparoscopists were achieved ( n = 8) , or control non-VR-trained ( n = 8) . All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status . Videotapes of gallbladder dissection were review ed independently by two investigators blinded to subject identity and training , and scored for eight predefined errors for each procedure minute ( interrater reliability of error assessment r > 0.80 ) . Results No differences in baseline assessment s were found between groups . Gallbladder dissection was 29 % faster for VR-trained residents . Non-VR-trained residents were nine times more likely to transiently fail to make progress ( P < .007 , Mann-Whitney test ) and five times more likely to injure the gallbladder or burn nontarget tissue ( chi-square = 4.27 , P < .04 ) . Mean errors were six times less likely to occur in the VR-trained group ( 1.19 vs. 7.38 errors per case;P < .008 , Mann-Whitney test ) . Conclusions The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy . This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment , training , error reduction , and certification of surgeons BACKGROUND The applications of minimally invasive surgery ( MIS ) and laparoscopy are rapidly exp and ing . Despite this expansion , our underst and ing of the importance of haptic feedback during laparoscopic surgery is incomplete . Although many surgeons believe that the use of minimally invasive techniques eliminates force feedback and tactile sensation ( haptics ) , the importance of haptics in MIS has not been fully evaluated . There is considerable interest in the development of simulators for MIS even though the importance of force feedback remains poorly understood . This study was design ed to determine the ability of experienced surgeons to interpret haptic feedback with respect to texture , shape , and consistency of an object . STUDY DESIGN A r and omized , single-blinded study was design ed . Twenty surgeons were presented objects in a r and om order , with participants blinded as to their identity . Inspection by direct palpation , conventional instruments , and laparoscopic instruments was performed on all objects . Statistic analysis of the data was performed using chi-square analysis and , when appropriate , a Fischer exact probability test . RESULTS Direct palpation was associated with the highest accuracy for shape identification and was superior to both conventional instruments ( p < 0.001 ) and laparoscopic instruments ( p<0.001 ) . Fine texture analysis with either a conventional instrument or a laparoscopic instrument was superior to direct palpation ( p < 0.05 ) . Finally , the three methods of analysis were comparable for consistency analysis . CONCLUSIONS These data indicate that laparoscopic instruments do , in fact , provide surgeons with haptic feedback . Interpretation of the texture , shape , and consistency of objects can be performed . In some situations , laparoscopic instruments appear to amplify the haptic information available . Our ongoing work is directed at further defining force interactions Background The use of a telemanipulator requires special training and surgical performance is associated with a learning curve . The aim of this study was to demonstrate the potential value of Haptic-Visual over Visual-Only passive Training in telemanipulator-assisted surgery . Methods Two telemanipulator consoles ( da Vinci , Intuitive Surgical ) were linked through an Application Programer 's Interface allowing the applicant at the training console to register the position and passively follow the motions of the instructor 's master telemanipulators ( MTMs ) at the master console ( Haptic-Visual Learning group , HVL ) . The applicant could not actively interfere with the MTM movements . Both the trainee and the instructor shared the same 3-dimensional vision . Alternatively , subjects received only st and ard visual training without touching the MTMs ( Visual-Only Learning group , VL ) . A st and ardized demonstration of tasks and the system was given for both groups . Participants ( n=20 ) without previous experience with telemanipulation performed a set of various tasks in a r and omized order . Study end points were time and accuracy required to perform the different task . Results The first task , with moving items to appropriate locations , showed differences in time to perform the task [ mean : 4:06 min ( HVL ) vs. 5:16 min ( VL ) ( P=0.2 ) ] and accuracy differed among groups [ mean number of errors 1.7 ( VL ) vs. 1.3 ( HVL ) P=0.38 ] . With more challenging tasks [ cut out round figures ( cut ) and performing double dot suture lines ( sti ) ] the number of errors was less in the HVL group [ mean : 1.1 errors ( cut ) ( P=0.05 ) and 1.8 errors ( sti ) ( P=0.26 ) ] compared with the VL group [ mean : 1.8 errors ( cut ) and 2.3 errors ( sti ) ] . In addition , the time to perform the tasks decreased in the HVL group with mean : 5.42 minutes ( cut ) ( P=0.26 ) and 9.41 minutes ( sti ) ( P=0.36 ) compared with the VL group with mean : 7.09 minutes ( cut ) and 11.43 minutes ( sti ) . Conclusions This study demonstrated the impact of haptic-visual passive learning in telemanipulator-assisted surgery which may alter the training for telemanipulator-assisted endoscopic procedures STUDY OBJECTIVE Minimally invasive surgery aims to achieve at least a similar clinical effectiveness with a quicker recovery than traditional open techniques . Although there have been numerous r and omized clinical trials comparing laparoscopic hysterectomy with hysterectomy by laparotomy , only a few studies have compared quality of life after different types of hysterectomy . None of these studies evaluated total laparoscopic hysterectomy . In this paper , we report on a r and omized comparison of quality of life after total laparoscopic versus total abdominal hysterectomy . DESIGN R and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Single-center teaching hospital in The Netherl and s. PATIENTS Patients scheduled for hysterectomy for a benign condition , in whom a vaginal hysterectomy was not possible and laparoscopic hysterectomy was feasible ( mobile uterus not exceeding the size of 18 weeks ' gestation ) . INTERVENTIONS Abdominal versus laparoscopic hysterectomy . MEASUREMENTS AND MAIN RESULTS Patients completed the Dutch version R AND -36 health survey preoperatively as well as at 5 time points in the first 12 weeks after surgery . The primary outcome of the study was quality of life as measured by the R AND -36 . A linear mixed model was used for statistical analysis while accounting for baseline values . Secondary outcomes were hospital stay and complications . There were 88 patients eligible , of whom 59 gave consent for r and omization . Twenty-seven women were allocated to the laparoscopic arm and 32 to the abdominal arm . We found a significant treatment effect favoring laparoscopic hysterectomy in the R AND -36 scale for vitality . Laparoscopic hysterectomy performed better on all other scales of the R AND -36 , but these differences were not statistically significant . CONCLUSIONS Laparoscopic hysterectomy results in more postoperative vitality when compared with abdominal hysterectomy . For this reason , all women with a benign condition requiring abdominal hysterectomy , in whom the laparoscopic approach is feasible , should have the chance to choose laparoscopic hysterectomy BACKGROUND Studies have demonstrated the beneficial effect of training novice laparoscopic surgeons using virtual reality ( VR ) simulators , although there is still no consensus regarding an optimal VR training curriculum . This study aims to establish and vali date a structured VR curriculum to provide an evidence -based approach for laparoscopic training programmes . METHODS The minimally invasive VR simulator ( MIST-VR ) has 12 abstract laparoscopic tasks , each at 3 graduated levels of difficulty ( easy , medium , and hard ) . Twenty medical students completed 2 sessions of all tasks at the easy level , 10 sessions at the medium level , and finally 5 sessions of the 2 most complex tasks at the hard level . At the medium level , subjects were r and omized into 2 equal groups performing either all 12 tasks ( group A ) or the 2 most complex tasks ( group B ) . Performance was measured by time taken , path length , and errors for each h and . The results were compared between groups , and to those of 10 experienced laparoscopic surgeons . RESULTS Baseline performance of both groups was similar at the easy level . At the medium level , learning curves for all 3 parameters reached plateau at the second ( group A , P < .05 ) and sixth ( group B , P < .05 ) repetitions . Performance at the hard level was similar between the 2 groups , and all achieved the pre-set expert criteria . CONCLUSION A graduated laparoscopic training curriculum enables trainees to familiarise , train and be assessed on laparoscopic VR simulators . This study can aid the incorporation of VR simulation into established surgical training programmes In order to develop effective virtual reality training systems for surgery there is a need to provide appropriate sensory and performance feedback to the user . This paper aims to demonstrate a method by which performance data can be collected . This is used to investigate the effect of haptic feedback on performance . A PHANTOM desktop device was used in conjunction with a suturing simulation A pair of needle-holders was instrumented with strain gauges and attached to the stylus of the PHANTOM allowing the measurement of force application and time . Suturing performance was evaluated in terms of stitch completion time , peak force application , and the length and straightness of the stitch . The effect of the level of force feedback provided by the simulation and performance over time was considered . The results indicate that the presence of force feedback affected task completion time , peak force application and the straightness of the stitch . Task completion time was shown to increase with the level of force feedback provided . Performance was seen to improve over time in terms of task completion time and the accuracy ofthe stitch . The work has examined how the presence and level of force feedback affects performance of a simple task . The accuracy of haptic feedback is important in the design of surgical simulation systems to ensure effective training transfer . A data collection method by which objective performance evaluation can be made is demonstrated . The method can be applied to training using bench models , simulations and potentially in the operating theatre Background In the literature of skill acquisition and transfer of skills , it often is assumed that the rate of skill acquisition depends on what has been learned in a similar context ( i.e. , surgical simulators providing haptic feedback ) . This study aim ed to analyze whether the addition of haptic feedback early in the training phase for image-guided surgical simulation improves performance . Methods A r and omized crossover study design was used , in which 38 surgical residents were r and omized to begin a 2-h simulator training session with either haptic or nonhaptic training followed by crossover after 1 h. The graphic context was a virtual upper abdomen . The residents performed two diathermy tasks . Two vali date d tests were used to control for differences in visual – spatial ability : the BasIQ general cognitive ability test and Mental Rotation Test A ( MRT-A ) . Results After 2 h of training , the group that had started with haptic feedback performed the two diathermy tasks significantly better ( p < 0.05 , unpaired t-test ) . Only the group that had started with haptic training significantly improved during the last 1-h session ( p < 0.01 , paired t-test ) . Conclusion The findings indicate that haptic feedback could be important in the early training phase of skill acquisition in image-guided surgical simulator training |
530 | 17,907,210 | Strong evidence was found for no long-term effectiveness on pain and self-reported physical function , moderate evidence for long-term effectiveness on patient global assessment of effectiveness , and conflicting evidence for observed physical function .
For exercise programs with additional booster sessions , moderate evidence was found for long-term effectiveness on pain , self-reported physical function , and observed physical function .
CONCLUSION The positive posttreatment effects of exercise therapy on pain and physical function in patients with OA of the hip and /or knee are not sustained in the long term .
Long-term effectiveness was only found for patient global assessment of effectiveness .
However , additional booster sessions after the treatment period positively influenced maintenance of beneficial posttreatment effects on pain and physical function in the long term | OBJECTIVE To determine the long-term effectiveness ( > /=6 months after treatment ) of exercise therapy on pain , physical function , and patient global assessment of effectiveness in patients with osteoarthritis ( OA ) of the hip and /or knee . | Although telephone and mail are often used to promote physical activity adoption , their ability to produce long-term maintenance is unclear . In this study , 140 men and women aged 50 - 65 years received 1 year of telephone counseling to adopt higher ( i.e. , more vigorous ) versus lower intensity ( i.e. , moderate ) exercise . After 1 year , participants were rer and omized to a 2nd year of contact via ( a ) telephone and mail or ( b ) predominantly mail . Participants who were prescribed higher intensity exercise and received predominantly mail had better exercise adherence during the maintenance year than those who received telephone and mail . Both strategies were similarly effective in promoting maintenance in the lower intensity condition . Results suggest that after successful adoption of physical activity with the help of telephone counseling , less intensive interventions are successful for physical activity maintenance in older adults Two studies were undertaken to compare strategies for the adoption and maintenance of moderate-intensity , home-based exercise training . In the study of adoption , 52 men and women who had served for 6 months as controls for a study of moderate-intensity , home-based exercise training received 30 minutes of baseline instruction . They were then r and omized to receive continuing instruction and support through 10 staff-initiated telephone contacts of 5 minutes each every 2 weeks , or to receive no telephone contacts . In subjects receiving telephone contacts , peak oxygen uptake increased significantly after 6 months , whereas no increase was observed in subjects receiving no staff support ( p less than 0.05 ) . In the maintenance study , 51 men and women who had significantly increased their peak oxygen uptake by 6 months of moderate-intensity , home-based exercise training were r and omized to undergo daily self-monitoring and receive adherence instructions , or undergo weekly self-monitoring only , during a second 6-month period of training . Subjects performing daily self-monitoring reported completing significantly more exercise training sessions during the 6 months of training than subjects performing weekly self-monitoring ; functional capacity in both groups remained higher than before training ( p less than 0.05 ) . Taken together , these studies suggest that brief baseline instruction followed by continuing telephone contact with staff can be used to help people adopt a moderate-intensity , home-based exercise training program that can be maintained by simple self-monitoring strategies The purpose of this study was to determine how an exercise adherence intervention affects the physiological , functional , and quality of life outcomes of patients with heart failure ( HF ) . Sixteen HF patients were r and omly assigned to an exercise-only group ( n = 8) or to an exercise-with-adherence group ( n = 8) . Two of the 16 people died from nonexercise related causes during the study and were not included in the analysis . The intervention was tested over a 24-week period in which patients participated in a 12-week supervised exercise program ( Phase 1 ) followed by 12 weeks of unsupervised home exercise ( Phase 2 ) . The intervention format was one of individualized graphic feedback on exercise goals and participation and problem-solving support by nurses . Results indicate that patients who received the intervention exercised more frequently and experienced improved outcomes during both phases . The adherence intervention may encourage HF patients to continue to exercise and thereby maintain the health benefits gained in both phases of an exercise program 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 Two behavioral techniques were assessed to determine their effects on subjects ' adherence to unsupervised exercise . The subjects were 35 moderately fit persons who had just completed an adult fitness program ( AF group ) and 42 sedentary individuals who were recruited through the campus newspaper ( NEWS group ) . Participants were r and omly assigned to one of three conditions : ( a ) self-monitoring , ( b ) reinforcement supplied by another person , or ( c ) control . All subjects were given instructions on how to exercise and asked to exercise on their own for 18 weeks . Self-monitoring subjects kept written records of their exercise behavior , while reinforcement subjects verbally reported their exercise behavior to another person who periodically administered rewards . Pre- and posttreatment tests on the NEWS group revealed no significant treatment or interaction effects . However , the reinforcement group had an 11 % improvement in predicted max VO2 and a 9 bpm improvement in exercise heart rate compared to 7.8 % , 5 bpm for the self-monitoring ( SM ) group and 5.3 % , 6 bpm for the control group . T-tests indicated that reward and SM groups improved significantly on these variables , whereas the control group did not . SM ( M = 2.07 ) and reinforcement ( M = 2.29 ) groups reported a significantly higher frequency of exercise per week than the control ( M = 1.36 ) group . The AF subjects were able to maintain their fitness level ( with the exception of a small increase in body fat ) over the 18-week period . The behavioral interventions had little differential effect on adherence by AF subjects who were already regular exercisers OBJECTIVES To determine the efficacy of community water-based therapy for the management of lower limb osteoarthritis ( OA ) in older patients . DESIGN A pre-experimental matched-control study was used to estimate efficacy of water-based exercise treatment , to check design assumptions and delivery processes . The main study was a r and omised controlled trial of the effectiveness of water-based exercise ( treatment ) compared with usual care ( control ) in older patients with hip and /or knee OA . The latter was accompanied by an economic evaluation comparing societal costs and consequences of the two treatments . SETTING Water exercise was delivered in public swimming pools in the UK . Physical function assessment s were carried out in established laboratory setting s. PARTICIPANTS 106 patients ( 93 women , 13 men ) over the age of 60 years with confirmed hip and /or knee OA took part in the preliminary study . A similar , but larger , group of 312 patients ( 196 women , 116 men ) took part in the main study , r and omised into control ( 159 ) and water exercise ( 153 ) groups . INTERVENTIONS Control group patients received usual care with quarterly semi-structured telephone interview follow-up only . The intervention in the main study lasted for 1 year , with a further follow-up period of 6 months . MAIN OUTCOME MEASURES Pain score on the Western Ontario and McMaster Universities OA index ( WOMAC ) . Additional outcome measures were included to evaluate effects on quality of life , cost-effectiveness and physical function measurements . RESULTS Short-term efficacy of water exercise in the management of lower limb OA was confirmed , with effect sizes ranging from 0.44 [ 95 % confidence interval ( CI ) 0.03 to 0.85 ] on WOMAC pain to 0.76 ( 95 % CI 0.33 to 1.17 ) on WOMAC physical function . Of 153 patients r and omised to treatment , 82 ( 53.5 % ) were estimated to have complied satisfactorily with their treatment at the 1-year point . This had declined to 28 ( 18 % ) by the end of the 6-month follow-up period , during which support for the intervention had been removed and those wishing to continue exercise had to pay their own costs for maintaining their exercise treatment . High levels of co-morbidity were recorded in both groups . Nearly two thirds of all patients had a significant other illness in addition to their OA . Fifty-four control and 53 exercise patients had hospital inpatient episodes during the study period . Water exercise remained effective in the main study but overall effect size was small , on WOMAC pain at 1 year , a reduction of about 10 % in group mean pain score . This had declined , and was non-significant , at 18 months . Mean cost difference estimates showed a saving in the water exercise group of pound123 - -175 per patient per annum and incremental cost-effectiveness ratios ranged from pound3838 to pound5951 per quality -adjusted life-year ( QALY ) . Net reduction in pain was achieved at a net saving of pound135 - -175 per patient per annum and the ceiling valuation of pound580 - -740 per unit of WOMAC pain reduction was favourably low . CONCLUSIONS Group-based exercise in water over 1 year can produce significant reduction in pain and improvement in physical function in older adults with lower limb OA , and may be a useful adjunct in the management of hip and /or knee OA . The water-exercise programme produced a favourable cost -- benefit outcome , using reduction in WOMAC pain as the measure of benefit . Further research is suggested into other similar public health interventions . Investigation is also needed into how general practice can best be supported to facilitate access to participants for research trials in healthcare , as well as an examination of the infrastructure and workforce capacities for physical activity delivery and the potential extent to which healthcare may be supported in this way . More detailed research is required to develop a better underst and ing of the types of exercise that will work for the different biomechanical subtypes of knee and hip OA and investigation is needed on access and environmental issues for physical activity programmes for older people , from both a provider and a participant perspective , the societal costs of the different approaches to the management of OA and longer term trends in outcome measures ( costs and effects ) OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis OBJECTIVE To investigate the therapeutic effects of different muscle-strengthening exercises on the functional status of patients with knee osteoarthritis ( OA ) . METHODS One hundred thirty-two patients with bilateral knee OA ( Altman Grade II ) were sequentially divided into 4 r and om groups ( GI to GIV ) . The patients in group I received isokinetic muscle-strengthening exercise , group II received isotonic muscle-strengthening exercise , group III received isometric muscle-strengthening exercise , and group IV acted as controls . The changes of muscle power of leg flexion and extension were measured with a Kinetic Communicator dynamometer , and patients ' functional status was evaluated by visual analogue scale , ambulation speed , and Lequesne index before and after treatment , and at the follow-up 1 year later . RESULTS The results showed that the patients with OA in each treated group had significant improvement in pain reduction , disability reduction , and in walking speed after treatment and at follow-up when compared with their initial status . Isotonic exercise had the greatest effect on pain reduction after treatment , and fewer participants discontinued the treatment because of exercise knee pain . Isokinetic exercise caused the greatest increase of walking speed and decrease of disability after treatment and at follow-up . The greatest muscle-strength gain in 60 degrees /second angular velocity peak torques was found in the isokinetic and isotonic exercise groups . A significant muscle-strength gain in 180 degrees /second angular velocity peak torques was found only in the isokinetic group after treatment . CONCLUSION AND RELEVANCE Isotonic exercise is suggested for initial strengthening in patients with OA with exercise knee pain , and isokinetic exercise is suggested for improving joint stability or walking endurance at a later time OBJECTIVE To determine whether gains in functioning observed immediately following participation in an 8-week program of supervised fitness walking for patients with knee osteoarthritis were sustained at 1-year followup . METHODS Twenty-nine ( 61.1 % ) of 47 original intervention program patients and 23 ( 51.1 % ) of 45 original control patients were interviewed by telephone at 1-year followup . Patients completed the Arthritis Impact Measurement Scales physical activity , arthritis impact , pain , medication use , and general health perceptions subscales , as well as a separate visual analog pain scale and measures of perceived self-efficacy to cope with arthritis pain and other symptoms . RESULTS Adherence to walking was low , and there were no statistically significant differences between intervention and control patients at one year . CONCLUSIONS The failure of intervention patients to maintain regular walking result ed in loss of functional benefits that were observed at 8 weeks in the original study . Long-term adherence to walking is critical to maintenance of initial gains in functional outcomes OBJECTIVE This study examined , in a group of older patients , ( a ) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and ( b ) the changes in self-reported physical activity and symptoms in patients with osteoarthritis ( OA ) . METHODS Healthy , sedentary community-dwelling men and women aged 60 years or more were invited to participate . Following r and om allocation , the intervention group received individualized physical activity advice at baseline and at 3 , 6 , and 12 months followup . RESULTS Of the 299 people who satisfied the study 's inclusion criteria , a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline . These patients reported increases in frequency and time of walking and vigorous exercise ( all P < 0.001 ) , with no change to OA symptom scores ( pain and stiffness ) , and a small decline in physical functioning was reported at 12 months followup in the control group only ( P = 0.027 ) . At the 12-month followup more intervention participants than control participants ( P = 0.013 ) reported a greater intention to exercise . CONCLUSIONS An offer of primary care-based physical activity advice , with an emphasis on the benefits for general health ( rather than " treatment " for OA ) , will attract individuals with OA symptoms . Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes , intention to exercise did appear to be positively influenced Osteoarthritis ( OA ) is a common chronic and progressive degenerative joint condition . A major consequence of knee OA is physical disability ; especially difficulty with activities requiring ambulation and transfer , which are necessary to maintain independence and a good quality of life . The purpose s of this study were to determine the efficacy of a muscle exercise program along with education about knee care , and investigate the clinical factors which influence its therapeutic efficacy . A prospect i ve study was carried out among elderly Thai people aged 60 years and over , living in an urban community of the Bangkok metropolitan area around Siriraj Hospital , between October 1997 and September 1999 . The number of elderly people with osteoarthritis of the knee was 392 ( male : female=86:306 ) with a mean age of 67.7+/-6 years . They were interviewed for demographic data and information about their symptoms . The range of the knee movement , quadriceps strength and the six-minute walking distance and a knee X-ray were evaluated . Group exercise was arranged twice a week for 8 weeks for the intervention group only . The results of the study revealed that the quadriceps strength in the intervention group had a tendency to increase and the walking distance was significantly improved especially in the first two months but there was a tendency to decline by the sixth and twelfth month after enrollment . On the other h and , there was no statistically significant difference of both important outcomes for the control group when assessed in the second month . The findings at the sixth and twelfth month after enrollment were that the quadriceps strength was slightly increased but the walking distance was decreased when compared with the initial assessment . An exercise frequency of 12 sessions in two months was sufficient to improve muscle strength and walking distance . Group exercise produces a significant improvement in strength and walking ability , especially in the first two months . Deterioration over time could be due to multiple factors , such as lack of regular exercise , lack of motivation , lack of family support or poor economic status , so we should encourage the elderly to exercise regularly OBJECTIVES To determine whether a functional-task exercise program and a resistance exercise program have different effects on the ability of community-living older people to perform daily tasks . DESIGN A r and omized , controlled , single-blind trial . SETTING Community leisure center in Utrecht , the Netherl and s. PARTICIPANTS Ninety-eight healthy women aged 70 and older were r and omly assigned to the functional-task exercise program ( function group , n=33 ) , a resistance exercise program ( resistance group , n=34 ) , or a control group ( n=31 ) . Participants attended exercise classes three times a week for 12 weeks . MEASUREMENTS Functional task performance ( Assessment of Daily Activity Performance ( ADAP ) ) , isometric knee extensor strength ( IKES ) , h and grip strength , isometric elbow flexor strength ( IEFS ) , and leg extension power were measured at baseline , at the end of training ( at 3 months ) , and 6 months after the end of training ( at 9 months ) . RESULTS The ADAP total score of the function group ( mean change 6.8 , 95 % confidence interval (CI)=5.2 - 8.4 ) increased significantly more than that of the resistance group ( 3.2 , 95 % CI=1.3 - 5.0 ; P=.007 ) or the control group ( 0.3 , 95 % CI=-1.3 - 1.9 ; P<.001 ) . Moreover , the ADAP total score of the resistance group did not change significantly compared with that of the control group . In contrast , IKES and IEFS increased significantly in the resistance group ( 12.5 % , 95 % CI=3.8 - 21.3 and 8.6 % , 95 % CI=3.1 - 14.1 , respectively ) compared with the function group ( -2.1 % , 95 % CI=-5.4 - 1.3 ; P=.003 and 0.3 % , 95 % CI=-3.6 - 4.2 ; P=.03 , respectively ) and the control group ( -2.7 % , 95 % CI=-8.6 - 3.2 , P=.003 and 0.6 % , 95 % CI=-3.4 - 4.6 ; P=.04 , respectively ) . Six months after the end of training , the increase in ADAP scores was sustained in the function group ( P=.002 ) . CONCLUSION Functional-task exercises are more effective than resistance exercises at improving functional task performance in healthy elderly women and may have an important role in helping them maintain an independent lifestyle OBJECTIVE To investigate the effects of ultrasound ( US ) in isokinetic muscle strengthening exercises on functional status of patients with knee osteoarthritis ( OA ) . DESIGN Effectiveness of isokinetic muscle strengthening exercises for treatment of periarticular soft tissue disorders was compared with and without pulsed and continuous US . SETTING Outpatient exercise program in a Taiwan medical university hospital . PARTICIPANTS One hundred twenty subjects with bilateral knee OA ( Altman grade II ) . INTERVENTION Subjects were r and omized sequentially into 1 of 4 groups . Group I received isokinetic muscular strengthening exercises , group II received isokinetic exercise and continuous US , group III received isokinetic exercise and pulsed US treatment , and group IV was the control group . MAIN OUTCOME MEASURES Therapeutic effects of isokinetic exercise were evaluated by changes in ambulation speed and the Lequesne index . In addition , changes in knee range of motion ( ROM ) , visual analog scale for pain , and muscle peak torques during knee flexion and extension were compared . Compliance in each group was recorded . RESULTS Each treated group had increased muscle peak torques and significantly reduced pain and disability after treatment and at follow-up . However , only patients in groups II and III had significant improvement in ROM and ambulation speed after treatment . Fewer participants in group III discontinued treatment due to knee pain during exercise . Patients in group III also showed the greatest increase in walking speed and decrease in disability after treatment and at follow-up . Gains in muscular strength in 60 degrees /s angular velocity peak torques were also noted in groups II and III . However , group III showed the greatest muscular strength gains with 180 degrees /s angular velocity peak torques after treatment and follow-up . CONCLUSIONS US treatment could increase the effectiveness of isokinetic exercise for functional improvement of knee OA , and pulsed ultrasound has a greater effect than continuous US OBJECTIVE To assess the effect of a program of supervised fitness walking and patient education on functional status , pain , and use of medication in patients with osteoarthritis of the knee . DESIGN An 8-week r and omized , controlled trial . SETTING Inpatient and outpatient services of an orthopedic hospital in an academic medical center . PATIENTS A total of 102 patients with a documented diagnosis of primary osteoarthritis of one or both knees participated in the study . Data were obtained on 47 of 51 intervention patients and 45 of 51 control patients . INTERVENTIONS An 8-week program of supervised fitness walking and patient education or st and ard routine medical care . MEASUREMENTS Patients were evaluated and outcomes assessed before and after the intervention using a 6-minute test of walking distance and scores on the physical activity , arthritis impact , pain , and medication subscales of the Arthritis Impact Measurement Scale ( AIMS ) . RESULTS Patients r and omly assigned to the walking program had a 70-meter increase in walking distance relative to their baseline assessment , which represents an improvement of 18.4 % ( 95 % Cl , 9.8 % to 27.0 % ) . In contrast , controls showed a 17-meter decrease in walking distance relative to their baseline assessment ( P less than 0.001 ) . Improvements in functional status as measured by the AIMS physical activity subscale were also observed in the walking group but not in the control group ( P less than 0.001 ) ; patients assigned to the walking program improved 39 % ( Cl , 15.6 % to 60.4 % ) . Although changes in scores on the arthritis impact subscale were similar in the two groups ( P = 0.093 ) , the walking group experienced a decrease in arthritis pain of 27 % ( Cl , 9.6 % to 41.4 % ) ( P = 0.003 ) . Medication use was less frequent in the walking group than in the control group at the post-test ( P = 0.08 ) . CONCLUSIONS A program of supervised fitness walking and patient education can improve functional status without worsening pain or exacerbating arthritis-related symptoms in patients with osteoarthritis of the knee OBJECTIVE To investigate physical function in patients with severe osteoarthritis ( OA ) of the knees during and after a general physical training program . DESIGN R and omized control trial , blinded observer , follow-up at 3 months and 1 year . SETTING Outpatient clinic . PATIENTS Consecutive sample of 25 patients ( 3 men , 22 women ) with OA of the knees according to the criteria of the American College of Rheumatology ( ACR ) . Two patients ( 8 % ) failed to complete the study . There were no withdrawals for adverse effects . INTERVENTION Twelve patients received training in groups of 6 , twice a week for 3 months . Training focused on general fitness , balance , coordination , stretching , and lower extremity muscle strength , and included a daily home exercise program . MAIN OUTCOME MEASURES Muscle strength across the knee ( extension and flexion ) , Algofunctional Index ( AFI ) , pain ( 0 to 10 point scale ) , walking speed , clinical findings . RESULTS Patients participated in 96 of 96 assessment s ( 100 % ) and in 218 of 280 training sessions ( 77.9 % ) . From baseline to 3 months , isokinetic quadriceps strength ( 30 degrees/sec ) improved 20 % ( confidence interval [ CI ] 2alpha = .05 , 8 % to 50 % ) in the least affected leg ; isometric strength improved 21 % . By 1 year , AFI had decreased 3.8 points ( CI2alpha = .05 , 1.0 to 7.0 ) , pain had decreased 2.0 points ( CI2alpha = 05 , 0.0 to 4.0 ) , and walking speed had increased 13 % ( CI2alpha = .05 , 4 % to 23 % ) . There was an increase in the frequency of palpable joint effusions ( p < .01 ) on the most affected side . Frequency of crepitus decreased on the least affected side ( p < .01 ) . CONCLUSIONS General physical training appears to be beneficial to patients with OA of the knee . As shown by the high compliance and low dropout frequency , such a program is feasible even in patients with severe OA of the knee Objectives : The aim of the study was to evaluate the therapeutic effect of electro-acupuncture ( EA ) and hydrotherapy , both in combination with patient education or with patient education alone , in the treatment of osteoarthritis in the hip . Methods : Forty-five patients , aged 42–86 years , with radiographic changes consistent with osteoarthritis in the hip , pain related to motion , pain on load , and ache were chosen . They were r and omly allocated to EA , hydrotherapy , both in combination with patient education , or patient education alone . Outcome measures were the disability rating index ( DRI ) , global self-rating index ( GSI ) , and visual analogue scale ( VAS ) . Assessment s were done before the intervention and immediately after the last treatment and 1 , 3 , and 6 months after the last treatment . Results : Pain related to motion and pain on load was reduced up to 3 months after last the treatment in the hydrotherapy group and up to 6 months in the EA group . Ache during the day was significantly improved in both the EA and hydrotherapy group up to 3 months after the last treatment . Ache during the night was reduced in the hydrotherapy group up to 3 months after the last treatment and in the EA group up to 6 months after . Disability in functional activities was improved in EA and hydrotherapy groups up to 6 months after the last treatment . Quality of life was also improved in EA and hydrotherapy groups up to 3 months after the last treatment . There were no changes in the education group alone . Discussion : In conclusion , EA and hydrotherapy , both in combination with patient education , induce long-lasting effects , shown by reduced pain and ache and by increased functional activity and quality of life , as demonstrated by differences in the pre- and post-treatment assessment |
531 | 24,551,055 | The P300 latency and amplitude follow a maturational path from childhood to adolescence , result ing in a period that marks a plateau , after which degenerative effects begin .
/ SIGNIFICANCE It is hypothesized that latency and amplitude index different aspects of brain maturation .
The P300 latency possibly indexes neural speed or brain efficiency .
The P300 amplitude might index neural power or cognitive re sources , which increase with maturation | BACKGROUND The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm , and has been associated with cognitive information processing ( e.g. memory , attention , executive function ) .
This paper review s the development of the auditory P300 across the lifespan . | The P300 ( P3 ) event-related brain potential was elicited in a group of 50 children and young adults ( 4 - 20 years ) . A simple auditory task was employed in which subjects indicated with a finger movement when a r and omly occurring target tone ( high pitch ) was presented in a series of st and ard ( low pitch ) tones . The probability of the target tone was varied across conditions at 10 % , 30 % , or 50 % to assess possible developmental changes in P300 amplitude . Memory capacity was assessed with forward and reverse digit spans . Circumference of the head also was measured . P300 latency decreased with age , and P300 amplitude tended to become larger with age . Polynomial regression analyses revealed significant quadratic trends in these relationships , with changes leveling off for older subjects . Digit span and head circumference also were related curvilinearly to P300 values . Multiple regression analysis indicated that changes in age and memory span both predicted significant changes in P300 latency and amplitude . Target stimulus probability generally affected all subjects in a similar fashion , although the strength of the correlational relationships tended to decline with increases in probability . Developmental changes for the N1 , P2 , and N2 components from the st and ard stimuli also were obtained . The results are discussed in terms of previous P3 findings for children and their implication s for future studies A new off-line procedure for dealing with ocular artifacts in ERP recording is described . The procedure ( EMCP ) uses EOG and EEG records for individual trials in an experimental session to estimate a propagation factor which describes the relationship between the EOG and EEG traces . The propagation factor is computed after stimulus-linked variability in both traces has been removed . Different propagation factors are computed for blinks and eye movements . Tests are presented which demonstrate the validity and reliability of the procedure . ERPs derived from trials corrected by EMCP are more similar to a ' true ' ERP than are ERPs derived from either uncorrected or r and omly corrected trials . The procedure also reduces the difference between ERPs which are based on trials with different degrees of EOG variance . Furthermore , variability at each time point , across trials , is reduced following correction . The propagation factor decreases from frontal to parietal electrodes , and is larger for saccades than blinks . It is more consistent within experimental sessions than between sessions . The major advantage of the procedure is that it permits retention of all trials in an ERP experiment , irrespective of ocular artifact . Thus , studies of population s characterized by a high degree of artifact , and those requiring eye movements as part of the experimental task , are made possible . Furthermore , there is no need to require subjects to restrict eye movement activity . In comparison to procedures suggested by others , EMCP also has the advantage that separate correction factors are computed for blinks and movements and that these factors are based on data from the experimental session itself rather than from a separate calibration session This study demonstrates that the EEG phenotypes as described by Johnstone , Gunkelman & Lunt are identifiable EEG patterns with good inter-rater reliability . Furthermore , it was also demonstrated that these EEG phenotypes occurred in both ADHD subjects as well as healthy control subjects . The Frontal Slow and Slowed Alpha Peak Frequency and the Low Voltage EEG phenotype discriminated ADHD subjects best from controls ( however the difference was not significant ) . The Frontal Slow group responded to a stimulant with a clinical ly relevant decreased number of false negative errors on the CPT . The Frontal Slow and Slowed Alpha Peak Frequency phenotypes have different etiologies as evidence d by the treatment response to stimulants . In previous research Slowed Alpha Peak Frequency has most likely erroneously shown up as a frontal theta sub-group . This implies that future research employing EEG measures in ADHD should avoid using traditional frequency b and s , but dissociate Slowed Alpha Peak Frequency from frontal theta by taking the individual alpha peak frequency into account . Furthermore , the divergence from normal of the frequency b and s pertaining to the various phenotypes is greater in the clinical group than in the controls . Investigating EEG phenotypes provides a promising new way to approach EEG data , explaining much of the variance in EEGs and thereby potentially leading to more specific prospect i ve treatment outcomes Event-related brain potentials ( ERPs ) of 13 - 21-year-old autistic subjects and age-matched controls were elicited by auditory stimuli in a variation of orienting response paradigms . Unexpected , novel sounds ( bizarre concoctions of human , mechanical and computer sounds ) were r and omly inserted as probes in a sequence of expected , non-novel sounds ( the word ' me ' ) . In order to help ensure that both subject groups were attending to this stream of information , each subject was required to press a button to a specified target sound ( the word ' you ' ) also r and omly inserted in the sequence of expected non-novel sounds . The ERP results showed that in both groups , unexpected , novel probes and also targets evoked a different neurophysiological response than did expected , non-novel sounds . This suggests that the autistic group did not misperceive novel information as non-novel and were able to make simple classification decisions as accurately as normal controls . However , in the autistic group , there may be less ' processing ' of the novel probes and of targets : compared to the control group , the autistic group had smaller amplitudes of two long-latency components to novels and smaller P3b amplitudes to targets . The two components to novels were termed A/Pcz/300 ( A = auditory ; P = positive ; cz = electrode site of maximum amplitude ; 300 = latency in msec ) and A/Ncz/800 . In another sequence of sounds , subjects simply listened to frequently presented ' me ' sounds ( 90 % ) and infrequently presented ' you ' sounds ( 10 % ) . In this no-task condition , no differences between autistic and normal control subjects were found |
532 | 26,438,429 | CONCLUSIONS Brief interventions promoting physical activity in primary care and the community are likely to be inexpensive compared with usual care .
Given the commonly accepted thresholds , they appear to be cost-effective on the whole , although there is notable variation between studies | null | null |
533 | 31,535,097 | Five years after loading , prosthetic and implant failures were similar between the two interventions , but complications and peri-implant marginal bone loss were higher and more severe at longer implants placed in vertically augmented m and ibles .
However in the meantime short implants could be the preferable option | PURPOSE To compare the clinical outcome of fixed prostheses supported by 4- to 8-mm-long implants with prostheses supported by longer implants placed in vertically augmented atrophic m and ibles after a follow-up of 5 years in function . | PURPOSE To evaluate the efficacy of short ( 5 or 6 mm long ) dental implants vs 10 mm or longer implants placed in crestally lifted sinuses . MATERIAL S AND METHODS Twenty partially edentulous patients with 5 to 7 mm of residual crestal height and at least 7 mm thickness below the maxillary sinuses as measured on computed tomography scans were r and omised according to a parallel group design to receive either one to two 5 or 6 mm long implants ( 10 patients ) or 10 mm long implants ( 10 patients ) after crestal sinus lifting and grafting with anorganic bovine bone . Implants were left to heal submerged for 4 months and were loaded with reinforced acrylic provisional prostheses , replaced , after 4 months , by definitive provisionally cemented or screw-retained metal-ceramic or metal-composite prostheses . Outcome measures were : prosthesis and implant failures , any complications , radiographic peri-implant marginal bone level changes , and patient 's satisfaction assessed by blinded assessors , when possible . All patients were followed up to 3 years after loading . RESULTS Two patients from the augmented group dropped out after the 1-year follow-up . No implant or prosthesis failure occurred . One short implant patient was affected by two complications vs one complication in the long implant group . There was no difference for patients experiencing complications between the two groups ( difference in proportions = -0.03 % ; 95%CI : -0.32 to 0.27 ; P = 1.000 ) . Short implants lost 0.89 ± 0.25 mm and long implants lost 1.08 ± 0.29 mm of peri-implant marginal bone 3 years after loading , the difference between the two groups being not statistically significant ( difference = -0.19 mm ; 95%CI : -0.46 to 0.09 ; P = 0.165 ) . All patients were fully or partially satisfied with function and fully satisfied with aesthetics . CONCLUSIONS Both techniques achieved excellent results and no differences were observed between prostheses supported by one to two 5 or 6 mm long implants vs 10 mm long in posterior atrophic maxillae up to 3 years after loading ; therefore it is up to clinicians to decide which procedure to use , although longer follow-ups with larger patient population s are needed to better underst and if one of these procedures could be more effective in the long-term . Conflict of interest statement : this study was partially supported by Zimmer Biomet . However , data property belonged to the authors , and by no means did the manufacturer interfere with the conduct of the trial or the publication of its results PURPOSE To compare the clinical outcome of immediately loaded cross-arch maxillary prostheses supported by zygomatic implants vs conventional implants placed in augmented bone . MATERIAL S AND METHODS A total of 71 edentulous patients with severely atrophic maxillas , who did not have sufficient bone volume to place dental implants or when it was possible to place only two implants in the front area ( minimal diameter 3.5 mm and length of 8 mm ) and less than 4.0 mm of bone height subantrally , were r and omised according to a parallel group design . They ( 35 patients ) received zygomatic implants to be loaded immediately vs grafting with a xenograft , followed , after 6 months of graft consolidation , by the placement of six to eight conventional dental implants , submerged for 4 months ( 36 patients ) . To be loaded immediately , zygomatic implants had to be inserted with an insertion torque superior to 40 Ncm . Screw-retained , metal-reinforced , acrylic provisional prostheses were provided to be replaced by definitive Procera Implant Bridge Titanium prostheses ( Nobel Biocare , Göteborg , Sweden ) with ceramic or acrylic veneer material s 4 months after initial loading . Outcome measures were : prosthesis , implant and augmentation failures , any complications , quality of life ( OHIP-14 ) , the number of days that patients experienced total or partial impaired activity , time to function , and number of dental visits , assessed by independent assessors . Patients were followed up to 4 months after loading . RESULTS No augmentation procedure failed . Three patients dropped out from the augmentation group . Six prostheses could not be delivered or failed in the augmentation group vs one prosthesis in the zygomatic group , the difference being statistically significant ( difference in proportions = 15.32 % ; P = 0.04 ; 95 % CI : 0.23 to 31.7 ) . Eight patients lost 35 implants in the augmentation group vs three implants in one patient from the zygomatic group , the difference being statistically significant ( difference in proportions = 21.38 % ; P = 0.001 ; 95 % CI : 3.53 to 39.61 ) . In total , 14 augmented patients were affected by 20 complications vs 26 zygomatic patients ( 35 complications ) , the difference being statistically significant ( difference in proportions = 31.87 % ; P = 0.008 ; 95 % CI : 6.48 to 53.37 ) . The OHIP-14 score was 3.68 ± 5.41 for augmented patients and 4.97 ± 5.79 for zygomatic patients , with no statistically significant differences between groups ( mean difference = 1.29 ; 95%CI -1.60 to 4.18 ; P = 0.439 ) . Both groups had significantly improved OHIP-14 scores from before rehabilitation ( P < 0.001 for both augmented and zygomatic patients ) . The number of days of total infirmity was , on average , 7.42 ± 3.17 for the augmented group and 7.17 ± 1.96 for the zygomatic group , the difference not being statistically significant ( mean difference = -0.25 ; 95 % CI : -1.52 to 1.02 ; P = 0.692 ) . Days of partial infirmity were on average 14.24 ± 4.64 for the augmented group and 12.17 ± 3.82 for the zygomatic group , the difference being statistically significant ( mean difference = -2.07 ; 95 % CI : -4.12 to -0.02 ; P = 0.048 ) . The mean number of days to have a functional prosthesis was 444.32 ± 207.86 for augmented patients and 1.34 ± 2.27 for zygomatic patients , the difference being statistically significant ( mean difference = -442.9 ; 95 % CI : -513.10 to -372.86 ; P < 0.001 ) . The average number of dental visits was 16.79 ± 10.88 for augmented patients and 12.58 ± 5.21 for zygomatic patients , the difference not being statistically significant ( mean difference = -4.21 ; 95 % CI -8.48 to 0.06 ; P = 0.053 ) . CONCLUSIONS Preliminary 4-months post-loading data suggest zygomatic implants were associated with statistically significantly less prosthetic ( one vs six patients ) and implant failures ( one patient lost three implants versus 35 implants in eight patients ) as well as time needed to functional loading ( 1.3 days vs 444.3 days ) when compared with augmentation procedures and conventionally loaded dental implants . Even if more complications were reported for zygomatic implants , which were solved spontaneously or could be h and led , zygomatic implants proved to be a better rehabilitation modality for severely atrophic maxillae . Long-term data are essential to confirm or dispute these preliminary results . Conflict of interest statement : This study was originally supported by Nobel Biocare , the manufacturer of the implants , and the provisional and definitive prosthetic components used in this study , which were provided free for the patients . However , before any results were known , Nobel Biocare withdrew the financial support and recruitment had to be stopped . Tecnoss ( Giaveno , Torino , Italy ) kindly donated the bone substitutes and the membranes , whereas Global D ( Brignais , France ) donated the osteo synthesis screws . Data property belonged to the authors and by no means did the manufacturers interfere with the publication of the results PURPOSE To evaluate whether 4.0 mm short dental implants could be an alternative to augmentation with xenographs in the maxilla and placement of at least 10.0 mm long implants in posterior atrophic jaws . MATERIAL S AND METHODS A group of 40 patients with atrophic posterior ( premolar and molar areas ) m and ibles with 5.0 mm to 6.0 mm bone height above the m and ibular canal and 40 patients with atrophic maxillas having 4.0 mm to 5.0 mm below the maxillary sinus , were r and omised according to a parallel group design to receive between one and three 4.0 mm long implants or one to three implants of at least 10.0 mm long in augmented bone , at two centres . All implants had a diameter of 4.0 mm or 4.5 mm . M and ibles were vertically augmented with inter-positional equine bone blocks and resorbable barriers . Implants were placed 4 months after the inter-positional grafting . Maxillary sinuses were augmented with particulated porcine bone via a lateral window covered with resorbable barriers , and implants were placed simultaneously . Implants were not submerged and were loaded after 4 months with provisional screw-retained reinforced acrylic restorations replaced after another 4 months by definitive screw-retained metal-composite prostheses . Patients were followed up to 1 year post-loading . Outcome measures were : prosthesis and implant failures , any complication , and peri-implant marginal bone level changes . RESULTS Three patients dropped out ; one from the maxillary augmented group , one from the m and ibular augmented group , and one from the maxillary short implant group . In six augmented m and ibles ( 30 % ) it was not possible to place implants of at least 10.0 mm , so shorter implants were placed instead . In m and ibles , one implant from the augmented group failed vs two 4.0 mm implants in two patients from the short implant group . In maxillae , three short implants failed in two patients vs seven long implants in four patients ( two long implants and one short implant dropped into the maxillary sinus ) . Two prostheses on short implants ( one m and ibular and one maxillary ) were placed at a later stage because of implant failures , vs six prostheses ( one m and ibular and five maxillary ) at augmented sites ( one m and ibular prosthesis not delivered , three maxillary prostheses delivered with delays , one not delivered , and one failed ) at augmented sites . In particular , three patients in the augmented group ( one m and ible and two maxillae ) were not wearing a prosthesis . There were no statistically significant differences in implant failures ( P ( chi-square test ) = 0.693 ; difference in proportion = 0.03 ; CI 95 % -0.11 to 0.17 ) or prostheses failures ( P ( chi-square test ) = 0.126 ; difference in proportion = 0.10 ; CI 95 % -0.03 to 0.24 ) . At m and ibular sites , nine augmented patients were affected by complications vs two patients treated with short implants ( P ( chi-square test ) = 0.01 ; difference in proportion = 0.37 ; CI 95 % 0.11 to 0.63 ) , the difference being statistically significant . No significant differences were found for maxillae : nine sinus-lifted patients vs four short implant patients were affected by complications ( P ( chi-square test ) = 0.091 ; difference in proportion = 0.25 ; CI 95 % -0.03 to 0.53 ) . At 1-year post-loading , average peri-implant bone loss was 0.51 mm at 4 mm long m and ibular implants , 0.77 mm at 10 mm or longer m and ibular implants , 0.63 mm at short maxillary implants and 0.72 mm at long maxillary implants . The difference was statistically significant in m and ibles ( mean difference -0.26 mm , 95 % CI -0.39 to -0.13 , P ( ANCOVA ) < 0.001 ) , but not in maxillae ( mean difference -0.09 mm , 95 % CI -0.24 to 0.05 , P ( ANCOVA ) = 0.196 ) . CONCLUSIONS One year after loading 4.0 mm long implants achieved similar results , if not better , than longer implants in augmented jaws , but were affected by fewer complications . Short implants might be a preferable choice over bone augmentation , especially in m and ibles , since the treatment is less invasive , faster , cheaper , and associated with less morbidity . However , 5 to 10 years post-loading data are necessary before making reliable recommendations PURPOSE To evaluate whether 5.0 × 5.0 mm dental implants with a novel nanostructured calcium-incorporated titanium surface could be an alternative to implants of at least 10.0 mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS Forty patients with atrophic posterior ( premolar and molar areas ) m and ibles with 5.0 mm to 7.0 mm bone height above the m and ibular canal , and 40 patients with atrophic maxillas with 4.0 mm to 6.0 mm below the maxillary sinus , were r and omised according to a parallel group design to receive between one and three 5.0 mm implants or one to three at least 10.0 mm-long implants in augmented bone at two centres . All implants had a diameter of 5.0 mm . M and ibles were vertically augmented with interpositional bovine bone blocks covered with resorbable barriers . Implants were placed after 4 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window covered with resorbable barriers , and implants were placed simultaneously . All implants were submerged and loaded after 4 months with provisional prostheses . Four months later , definitive screw-retained or provisionally cement metal-ceramic or zirconia prostheses were delivered . Patients were followed to 3 years post-loading and the outcome measures were : prosthesis and implant failures , any complication , and peri-implant marginal bone level changes . RESULTS Seven patients dropped out before the 3-year evaluation ( two short m and ibles , one short maxilla , two augmented m and ibles and two augmented maxillae ) . In m and ibles , two grafted patients were not prosthetically rehabilitated because of multiple complications and two implants failed in the same patient ( the second was a replacement implant ) vs one patient who lost a short implant and crown 2 years after loading . In maxillas one short implant failed with its provisional crown 3 months post-loading . There were no statistically significant differences in prostheses ( difference in proportion = 0.001 ; 95 % CI : -0.12 to 0.13 ; P = 1.000 ) and implant failures ( difference in proportion = 0.00 ; 95 % CI : -0.13 to 0.13 ; P = 1.000 ) up to 3 years after loading . Significantly , more complications occurred at m and ibular grafted sites : 17 augmented patients were affected by complications vs eight patients treated with short implants in m and ibles ( difference in proportion = 0.43 ; 95 % CI : 0.13 to 0.64 ; P = 0.008 ) . In the maxilla , six sinus-lifted patients vs two patients treated with short implants were affected by complications ; the difference not being statistically significant ( difference in proportion = 0.21 ; 95 % CI : -0.05 to 0.45 ; P = 0.232 ) . Patients with m and ibular short implants lost on average 1.10 mm of peri-implant bone at 3 years and patients with 10.0 mm or longer m and ibular implants lost 1.39 mm . Patients with maxillary short implants lost on average 1.04 mm of peri-implant bone at 3 years and patients with 10 mm or longer maxillary implants lost 1.43 mm . Longer implants showed a greater bone loss up to 3 years after loading than short implants both in maxillae ( mean difference : -0.39 mm ; 95 % CI : -0.70 to -0.07 mm ; P = 0.017 ) and in m and ibles ( mean difference : -0.29 mm ; 95 % CI : -0.53 to -0.05 mm ; P = 0.020 ) . CONCLUSIONS Three years after loading , 5.0 mm × 5.0 mm implants achieved similar results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity . However , 5- to 10-year post-loading data are necessary before making reliable recommendations PURPOSE This study aims to test whether or not veneering of the submucosal part of zirconia abutments with pink dental ceramic affects radiographic and technical outcomes of implant-supported single crowns ( ISSC ) . MATERIAL S AND METHODS Single tooth implants were r and omly restored with either pink-veneered zirconia abutments ( test ; n = 10 ) or non-veneered zirconia abutments ( control group ; n = 10 ) and all-ceramic crowns . At baseline ( crown insertion ) , and 6- and 12-month radiographic and technical evaluations were performed including st and ardized x-rays and modified United States Public Health Service criteria ( technical ) . Survival and complication rates were assessed for implants and restorations . Robust linear mixed model analysis was performed to investigate the effect of group and time-point on radiographic outcomes . RESULTS At 1 year , the survival rate for implants was 100 % and 95 % for ISSC . Most of the implants were placed subcrestally . Therefore , mean marginal bone levels decreased in both groups between implant insertion and baseline ( p < .05 ) , but then remained stable up to 1 year ( test : 0.15 mm ± 0.42 mm ; control 0.23 mm ± 0.63 mm ) ( p > .005 ) . At 6 months , one minor chipping occurred in the test group . At 1 year , three crowns ( control ) exhibited occlusal roughness . In addition , one abutment fracture occurred ( test ) . The differences between test and control group were not statistically significantly different for any of the evaluated outcome measures ( p > .05 ) . CONCLUSIONS Veneering of the submucosal part of zirconia abutments did not affect biological and technical outcomes of ISSCs . Technical complications of the reconstructions , however , were frequent , result ing in a rate of 75 % of the crowns being complication free PURPOSE To evaluate whether 6 mm long by 4 mm wide dental implants could be an alternative to implants at least 10 mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS A total of 20 patients with bilateral atrophic m and ibles and 20 patients with bilateral atrophic maxillae , having 5 to 7 mm of bone height above the m and ibular canal or below the maxillary sinus , had each side of the jaws r and omly allocated according to a split-mouth design . They were allocated to receive one to three 6 mm long and 4 mm wide implants , or implants at least 10 mm long in augmented bone by two different surgeons in different centres . M and ibles were vertically augmented with interpositional equine bone blocks and resorbable barriers , and implants were placed 3 months later . Maxillary sinuses were augmented with particulated porcine bone via a lateral window and implants were placed simultaneously . All implants were submerged and loaded , after 4 months , with provisional prostheses . Four months later , definitive metal-ceramic prostheses were delivered . Outcome measures were prosthesis and implant failures , any complication and radiographic peri-implant marginal bone level changes . RESULTS One patient treated in the m and ible dropped out before the 1-year post-loading follow-up . All maxillary implants and prostheses were successful , whereas 2 m and ibular prostheses could not be placed on implants at least 10 mm long due to graft failures ; one was associated with the loss of 3 implants because of infection . There were no statistically significant differences in implant and prosthesis failures , though significantly more complications occurred at grafted sites in m and ibles ( P = 0.0078 ) , but not in maxillae ( P = 0.1250 ) . In total , 14 complications occurred in 12 patients at augmented sites versus none at 6 mm-long implants . All failures and complications occurred before loading . Patients with m and ibular 6 mm-long implants lost an average of 1.05 mm of peri-implant bone at 1 year and patients with m and ibular implants at least 10 mm long lost 1.07 mm . These differences were statistically significant ( P < 0.001 ) . Patients with maxillary 6 mm-long implants lost an average of 1.02 mm of peri-implant bone at 1 year and patients with maxillary implants at least 10 mm long lost 1.09 mm . These differences were statistically significant ( P < 0.001 ) . There were no statistically significant differences in bone level changes up to 1 year between 6 mm and at least 10 mm-long implants in both jaws ( m and ibles n = 18 , mean difference -0.02 mm , 95 % CI -0.16 to 0.12 , P = 0.7384 ; maxillae n = 20 , mean difference -0.07 mm , 95 % CI -0.18 to 0.05 , P = 0.2547 ) . CONCLUSIONS Short-term data ( 1 year after loading ) indicate that 6 mm-long implants with a conventional diameter of 4 mm achieved similar if not better results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation , especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity . However , data obtained 5 to 10 years after loading are necessary before making reliable recommendations . CONFLICT OF INTEREST STATEMENT : Tecnoss and Southern Implants partially supported this trial and donated bio material s , implants and prosthetic components used in this study . However , the data belonged to the authors and by no means did the manufacturers interfere with the conduct of the trial or the publication of its results OBJECTIVES To evaluate whether 7-mm-long implants could be an alternative to longer implants placed in vertically augmented posterior m and ibles . MATERIAL S AND METHODS Sixty patients with posterior m and ibular edentulism with 7 - 8 mm bone height above the m and ibular canal were r and omized to either vertical augmentation with anorganic bovine bone blocks and delayed 5-month placement of ≥10 mm implants or to receive 7-mm-long implants . Four months after implant placement , provisional prostheses were delivered , replaced after 4 months , by definitive prostheses . The outcome measures were prosthesis and implant failures , any complications and peri-implant marginal bone levels . All patients were followed to 1 year after loading . RESULTS One patient dropped out from the short implant group . In two augmented m and ibles , there was not sufficient bone to place 10-mm-long implants possibly because the blocks had broken apart during insertion . One prosthesis could not be placed when planned in the 7 mm group vs. three prostheses in the augmented group , because of early failure of one implant in each patient . Four complications ( wound dehiscence ) occurred during graft healing in the augmented group vs. none in the 7 mm group . No complications occurred after implant placement . These differences were not statistically significant . One year after loading , patients of both groups lost an average of 1 mm of peri-implant bone . There no statistically significant differences in bone loss between groups . CONCLUSIONS When residual bone height over the m and ibular canal is between 7 and 8 mm , 7 mm short implants might be a preferable choice than vertical augmentation , reducing the chair time , expenses and morbidity . These 1-year preliminary results need to be confirmed by follow-up of at least 5 years PURPOSE To evaluate whether 5 mm short dental implants could be an alternative to augmentation with anorganic bovine bone and placement of at least 10 mm long implants in posterior atrophic jaws . MATERIAL S AND METHODS Fifteen patients with bilateral atrophic m and ibles ( 5 - 7 mm bone height above the m and ibular canal ) , and 15 patients with bilateral atrophic maxillae ( 4 - 6 mm bone height below the maxillary sinus ) and bone thickness of at least 8 mm , were r and omised according to a splitmouth design to receive one to three 5 mm short implants or at least 10 mm long implants in augmented bone . M and ibles were vertically augmented with interpositional bone blocks and maxillary sinuses with particulated bone via a lateral window . Implants were placed after 4 months , submerged and loaded , after 4 months , with provisional prostheses . Four months later , definitive provisionally cemented prostheses were delivered . Outcome measures were : prosthesis and implant failures , any complication and peri-implant marginal bone level changes . RESULTS In 5 augmented m and ibles , the planned 10 mm long implants could not be placed and shorter implants ( 7 and 8.5 mm ) had to be used instead . One year after loading no patient dropped out . Two long ( 8.5 mm in the m and ible and 13 mm in the maxilla ) implants and one 5 mm short maxillary implant failed . There were no statistically significant differences in failures or complications . Patients with short implants lost on average 1 mm of peri-implant bone and patients with longer implants lost 1.2 mm . This difference was statistically significant . CONCLUSIONS This pilot study suggests that 1 year after loading , 5 mm short implants achieve similar if not better results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation since the treatment is faster , cheaper and associated with less morbidity , however their long-term prognosis is unknown OBJECTIVES To evaluate whether 6.6-mm long implants could be a suitable alternative to longer implants placed in vertically augmented atrophic posterior m and ibles . MATERIAL S AND METHODS Sixty partially edentulous patients having 7 to 8 mm of residual crestal height and at least 5.5 mm thickness measured on CT scans above the m and ibular canal were r and omised according to a parallel group design . They were either to receive 1 to 3 submerged 6.6-mm long implants or 9.6 mm or longer implants ( 30 patients per group ) placed in vertically augmented bone . Bone was augmented with interpositional anorganic bovine bone blocks covered by resorbable barriers . Grafts were left to heal for 5 months before implant placement . Four months after provisional acrylic prostheses were delivered , they were replaced , after 4 months , by definitive metal-ceramic prostheses . Outcome measures were : prosthesis and implant failures ; complications ; and radiographic peri-implant marginal bone level changes . All patients were followed up to 5 years after loading . RESULTS Five years after loading , 8 patients dropped out : 3 from the short implant group and 5 from the augmented group . The augmentation procedure failed in 2 patients and only 6.6-mm long implants could be inserted . There were no statistically significant differences for prosthesis and implant failures . Five prostheses failed in 4 patients of the short implant group versus 5 prostheses in 5 patients in the augmented group ( Fishers exact test P = 1.0 ; difference in proportions = 0.07 ; 95 % CI -0.29 to 0.43 ) . Five short implants failed in 3 patients versus 3 long implants in 3 patients ( Fishers exact test P = 1.00 difference in proportions = 0.00 ; 95 % CI -0.43 to 0.43 ) . There were statistically more complications in augmented patients ( 25 complications in 21 augmented patients versus 6 complications in 6 patients of the short implant group ) ( Fishers exact test P < 0.0001 ; difference in proportions = 0.60 ; 95 % CI 0.38 , 0.82 ) . Both groups gradually lost peri-implant bone in a statistically significant way . Five years after loading , short implant group patients lost an average of 1.49 mm peri-implant bone compared with 2.34 mm in the augmented group . Short implants experienced statistically significantly less bone loss ( 0.82 mm , 95 % CI 0.48 ; 1.16 , P < 0.0001 ) than long implants . CONCLUSIONS When residual bone height over the m and ibular canal is between 7 to 8 mm , 6.6 mm short implants could be an interesting alternative to vertical augmentation in posterior atrophic m and ibles since the treatment is faster , cheaper and associated with less morbidity . Longer follow-ups may still be needed to confirm these results , however the medium-term prognosis ( 5 years after loading ) of short implants is at least as good as those of longer implants placed vertically in augmented m and ibles PURPOSE The aim of this r and omised controlled trial was to assess the clinical performance of single crowns in the posterior maxilla supported by either 6-mm or 11-mm implants combined with maxillary sinus floor elevation . MATERIAL S AND METHODS 41 consecutive patients with one missing premolar or molar in the posterior maxilla and with an estimated bone height of 6 to 8 mm in that area were included . Each patient was r and omly allocated to one of the two treatment groups , namely to receive an 11-mm implant ( Osseo Speed 4.0 S , Dentsply Implants , Mölndal , Sweden ) in combination with maxillary sinus floor elevation surgery or to receive a 6-mm implant ( Osseo Speed 4.0 S ) without any grafting . After a 3-month osseointegration period , all implants were restored with custom-made titanium abutments and cemented zirconia-based porcelain crowns . Outcome measures were : implant survival ; radiographic bone changes ; plaque accumulation ; bleeding tendency ; peri-implant inflammation ; presence of dental calculus ; biological and technical complications ; and patients ' satisfaction . Clinical and radiographic examinations were performed at placement of the crown and 12 months thereafter . Patients ' satisfaction was scored before treatment and after 12 months of functioning of the crown . RESULTS One patient of the 11 mm implant group died during the follow-up . No implant failed and no biological or technical complications occurred . From loading to the 12 months follow-up , no difference was found in mean marginal bone changes between the groups ( bone resorption in both groups 0.1 ± 0.3 mm ) . Clinical items revealed very healthy peri-implant soft tissues in both groups . Patients ' satisfaction scores were high in both groups . CONCLUSIONS 6-mm implants and 11-mm implants combined with sinus floor elevation surgery are equally successful to support a single crown in the resorbed posterior maxilla after 1-year follow-up BACKGROUND Different treatment strategies for the atrophied m and ible are described in literature . The need for long term care and aftercare for these strategies is sparsely described , however . PURPOSE To prospect ively assess the need for prosthetic and surgical care and aftercare of two implant treatment strategies for the atrophied m and ible . MATERIAL S AND METHODS Forty edentulous elderly patients were r and omly assigned according to a balanced allocation method to a treatment strategy : dental implants in combination with an augmentation procedure versus a nonaugmentation procedure . All surgical and prosthetic care and aftercare were scored from the first visit until 15 years after implant placement . RESULTS Twenty elderly patients completed the 15-year follow-up . As expected , the augmentation group needed significantly more surgical time than the nonaugmentation group ( 338 vs 145 minutes ) , but the need for prosthetic care and surgical/prosthetic aftercare was comparable . Implant survival was lower in augmented m and ibles ( 88.7 % vs 98.7 % , p < .05 ) . Aftercare mainly consisted of routine inspections ; the need for prosthetic adjustments was minor . Surgical aftercare was hardly needed . CONCLUSION The only difference in the need for surgical and prosthetic ( after ) care was the extra time needed for performing augmentation surgery and the higher risk on implant loss in augmented m and ibles . Otherwise , the need for care and aftercare was of the same magnitude . Thus , when applicable , nonaugmentation surgery is preferred as no general anesthesia is needed and the morbidity is low PURPOSE To evaluate whether 7-mm-long implants could be a suitable alternative to longer implants placed in vertically augmented bone for the treatment of atrophic posterior m and ibles . MATERIAL S AND METHODS Sixty partially edentulous patients having 7 to 8 mm of residual crestal height and at least 5.5 mm thickness measured on a computed tomography scan above the m and ibular canal were r and omised to receive either two to three submerged 7-mm-long NanoTite External Hex implants ( Biomet 3i ) or 10-mm or longer implants ( 30 patients per group ) placed in vertically augmented bone . Bone was augmented with anorganic bovine bone blocks ( Bio-Oss ) using a s and wich technique and resorbable barriers . The grafts were left healing for 5 months before placing the implants , which were submerged . Four months after implant placement , provisional acrylic prostheses were delivered . Definitive screw-retained metal-ceramic prostheses were delivered 4 months later . Outcome measures were : prosthesis and implant failures , any complications , and time needed to fully recover mental nerve sensitivity . All patients were followed up to the delivery of the final restorations ( 4 months after loading ) . RESULTS No patient dropped out . In two patients of the augmented group , there was not enough space to place 10-mm or longer implants as planned and 7-mm-long implants were used instead . The most likely reason for this is that the Bio-Oss blocks fractured in many pieces at placement . One prosthesis could not be placed when planned in the 7-mm group versus three prostheses in the augmented group , because of failure of one implant in each patient . The difference was not statistically significant . All implants were successfully replaced and final prostheses delivered . Four complications ( wound dehiscence ) occurred during graft healing in the augmented group ( one possibly associated with the failure of one implant ) versus none in the 7-mm-long implant group . The difference was not statistically significant . No patient suffered from permanent paraesthesia of the alveolar inferior nerve ; however , sensitivity was recovered significantly faster in the short implant group . CONCLUSIONS The early results of this study suggest that , when the residual bone height over the m and ibular canal is between 7 and 8 mm , 7-mm short implants might be a preferable choice since the treatment is faster , cheaper and associated with less morbidity than vertical bone augmentation . These preliminary results must be confirmed by follow-ups of 5 years or more in order to monitor the performance of short implants over time PURPOSE To evaluate whether 5 × 5 mm dental implants with a novel nanostructured calciumincorporated titanium surface could be an alternative to implants at least 10 mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS A total of 40 patients with atrophic posterior ( premolar and molar areas ) m and ibles having 5 to 7 mm of bone height above the m and ibular canal and 40 patients with atrophic maxillae having 4 to 6 mm below the maxillary sinus , were r and omised according to a parallel group design to receive one to three 5 mm implants or one to three at least 10 mm-long implants in augmented bone at two centres . All implants had a diameter of 5 mm . M and ibles were vertically augmented with interpositional bovine bone blocks and resorbable barriers . Implants were placed after 4 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window covered with resorbable barriers and implants were placed simultaneously . All implants were submerged and loaded after 4 months with provisional prostheses . Four months later , definitive screw-retained or provisionally cemented metal-ceramic or zirconia prostheses were delivered . Patients were followed up to 1 year post-loading and the outcome measures were prosthesis and implant failures , any complications and peri-implant marginal bone level changes . RESULTS One maxillary grafted patient dropped out before the 1-year evaluation . In m and ibles , 1 grafted patient did not want to go ahead with the treatment because of multiple complications and graft failure , and another grafted patient did not receive his prostheses due the loss of 2 implants . In maxillae , one 5 × 5 mm implant failed with its provisional crown 3 months post-loading . There were no statistically significant differences in prostheses and implant failures . Significantly more complications occurred at both m and ibular and maxillary grafted sites : 17 augmented patients were affected by complications versus 8 patients treated with short implants in the m and ible ( P = 0.0079 ; difference in proportion = -0.45 ; 95 % CI -0.67 to -0.15 ) , and 5 sinus-lift patients versus none treated with maxillary short implants ( P = 0.047 ; difference in proportion = -0.25 ; 95 % CI -0.44 to -0.06 ) . Patients with m and ibular short implants lost on average 0.94 mm of peri-implant bone at 1 year and patients with 10 mm or longer m and ibular implants lost 1.03 mm . Patients with maxillary short implants lost on average 0.87 mm of peri-implant bone at 1 year and patients with 10 mm or longer maxillary implants lost 1.15 mm . There were no statistically significant differences in bone level changes up to 1 year between short and longer implants in maxillae ( mean difference -0.28 mm , 95 % CI -0.56 to 0.01 , P = 0.051 ) and in m and ibles ( mean difference -0.09 mm , 95 % CI -0.26 to 0.08 , P = 0.295 ) . CONCLUSIONS One year after loading , 5 × 5 mm implants achieved similar results compared to longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity , however 5 to 10 years of post-loading data are necessary before making reliable recommendations . CONFLICT-OF-INTEREST STATEMENT MegaGen partially supported this trial and donated implants and prosthetic components used in this study , whereas Tecnoss donated the bio material s. The data belonged to the authors and by no means did the manufacturers interfere with the conduct of the trial or the publication of its results PURPOSE To evaluate the efficacy of long implants ( 10 - 16 mm ) inserted in maxillary sinuses augmented according to a lateral approach versus short ( 8 mm ) implants placed in crestally augmented sinuses , early loaded after 45 days . MATERIAL S AND METHODS Forty partially or fully edentulous patients having 3 to 6 mm of residual crestal height and at least 4 mm in thickness below the maxillary sinuses were r and omised according to a parallel group design to receive either one to three 10 to 16 mm-long hydroxyapatite-coated implants ( 20 patients ) after lateral sinus lifting with 50 % an organic bovine ( Bio-Oss ) and 50 % autogenous bone , or 8 mm implants ( 20 patients ) after crestal sinus lifting with autogenous bone . Implants were submerged and left healing for 45 days before loading the implants . Within 1 week after abutment connection , implants were loaded with screw-retained full acrylic provisional prostheses . Definitive metal-ceramic prostheses were provisionally cemented 45 days after abutment connection . Outcome measures were prosthesis and implant failures , any complications , and radiographic periimplant marginal bone level changes . In addition , the stability of individual implants was assessed with Osstell and Periotest at abutment connection ( baseline ) , and at 1 and 5 years after loading by blinded outcome assessors . All patients were followed up to 5 years after loading . RESULTS One patient dropped out ( death ) from the longer implant group . One implant failed in the short implant group versus 5 implants in 3 patients of the longer implant group . The difference was not statistically significant . Four complications occurred in 4 patients of the short implant group versus 8 complications in 7 patients of the long implant group , the difference being not statistically significantly different . However , the 2 major postoperative complications occurred in the longer implant group : 1 abscess , and 1 sinusitis that led to the complete failure of the treatment in 2 patients ( 4 implants lost ) . A total of 0.72 mm of peri-implant marginal bone was lost after 5 years at long implants and 0.41 mm at short implants , the difference between the two groups was statistically significant ( P = 0.028 ) . Osstell values increased and Periotest decreased over time and there were no differences between groups at any time points . CONCLUSIONS In atrophic maxillary sinuses with a residual bone height of 3 to 6 mm , 8 mm short implants placed in a simultaneously crestally lifted sinus might be a preferable choice than a 1-stage lateral sinus lift for placing longer implants since they appear to be associated with less morbidity . If these implants are placed with an insertion torque > 35 Ncm and are joined together under the same prosthesis , they can be early loaded at 6 weeks OBJECTIVES To compare the effectiveness of onlay bone blocks of equine origin ( test or XB group ) with autogenous bone blocks ( control or AB group ) harvested from the ramus or the iliac crest for the rehabilitation of partially or fully edentulous atrophic jaws with implant supported prostheses . MATERIAL S AND METHODS Forty patients with partially or fully edentulous atrophic jaws having less than 5 mm of residual crestal bone height and /or less than 3 mm of bone thickness , as measured on computerised tomography ( CT ) scans , were r and omised into two groups according to a parallel group design , either to be augmented with autogenous onlay bone blocks ( 20 patients ; AB group ) from the m and ibular ramus or the iliac crest , or with onlays blocks of spongious bone of equine origin ( 20 patients ; XB group ) . Two centres treated 20 patients each . Six XB blocks were modelled on lithographic models of the jaws before grafting . The blocks were fixed with screws and osteo synthesis plates and were covered with resorbable barriers made of equine cortical bone and fixed with tacks . The autogenous bone grafts were left to heal for 4 months and the xenografts for 7 months before placing implants , which were submerged . After 4 months , either bar-retained overdentures or provisional reinforced acrylic prostheses were delivered . Provisional prostheses were replaced , after 4 months , by definitive fixed prostheses . Outcome measures were : prosthesis and implant failures ; complications ; patient satisfaction ; pain recorded 3 and 10 days post-augmentation ; number of days of hospitalisation , total and partial infirmity days . All patients were followed for 4 months after loading . RESULTS All patients could be rehabilitated with implant-supported prostheses and none dropped out . Twenty-eight patients were augmented in the maxilla ( 15 with AB and 13 with XB ) and 12 in the m and ible ( 5 with AB and 7 with XB ) . No AB graft failed totally versus 10 XB grafts ( difference = 0.5 ; 95 % CI 0.23 to 0.68 ; P = 0.0004 ) . In particular , all 7 XB m and ibular grafts and 5 out of 6 XB blocks ( 3 in m and ibles and 2 in maxillas ) , which were previously modelled on lithographic models of the jaws failed . One implant failed in one AB patient versus 11 implants in 4 XB patients ( P = 0.3416 ) . All but 1 prostheses were loaded in time in the AB patients , versus 4 prostheses which were loaded with delays in XB patients because of graft and implant failures ( P = 0.3416 ) . Four complications occurred in 4 AB patients versus 15 complications in 12 XB patients ( difference = 0.4 ; 95 % CI 0.09 to 0.63 ; P = 0.0225 ) . Fourteen AB patients reported moderate pain 3 days postoperatively versus 6 XB patients ( P = 0.0562 ) ; at 10 days , 10 AB patients reported moderate pain versus 1 XB patient ( difference = -0.45 ; 95 % CI -0.65 to -0.17 ; P = 0.0033 ) . The 14 patients harvested from the iliac crest were hospitalised for an average of 3.1 nights , whereas 7 patients treated with XB were hospitalised on average for 1.4 nights ( P < 0.0001 ) . The number of total and partial infirmity days was 126 for theAB group and 43 for the XB group , and 220 for the AB group and 93 for the XB group , respectively ( mean day difference = -4.15 ; 95 % CI -7.35 to -0.95 ; P = 0.0134 and mean day difference = -5.7 ; 95 % CI -10.01 to -1.39 ; P = 0.0116 , respectively ) . Seventeen AB patients versus 19 XB patients were fully satisfied with function of their prostheses ( P = 0.6050 ) , 18 AB patients versus 12 XB patients were fully satisfied with aesthetics of their prostheses ( P = 0.0648 ) , and 5 and 3 patients , respectively would not undergo the same procedure again ( P = 0.6948 ) . There were no differences between the outcomes of the two centres with exception of prosthesis failures and complications in the maxilla . CONCLUSIONS Autogenous onlay bone blocks are superior to equine onlay bone blocks , especially in m and ibles , where all equine blocks failed , therefore we strongly discourage the use of onlay bone blocks of equine origin in m and ibles PURPOSE To evaluate whether 6 mm-long by 4 mm-wide dental implants could be an alternative to at least 10 mm-long implants placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS Twenty patients with bilateral atrophic m and ibles and 20 patients with bilateral atrophic maxillae , having 5 to 7 mm of bone height above the m and ibular canal or below the maxillary sinus , were r and omised according to a split-mouth design to receive one to three 6 mm-long and 4 mm-wide implants or at least 10-mm long implants in augmented bone at two centres . M and ibles were vertically augmented with interpositional equine bone blocks and resorbable barriers , and implants were placed after 3 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window and implants were placed simultaneously . All implants were submerged and loaded , after 4 months , with provisional prostheses . Four months later , definitive screw-retained metal-ceramic prostheses were delivered . Outcome measures were prosthesis and implant failures , any complication , time needed to fully recover mental nerve function ( only for m and ibular implants ) and patient preference . RESULTS All screened patients had sufficient bone width to support 4 mm-diameter implants . Patients were followed up to 5 months post-loading and none dropped out . There were no statistically significant differences in graft , implant or prosthesis failures , though significantly more intra- and postoperative complications occurred at grafted sites . Fourteen complications occurred in 12 patients at augmented sites versus none at short implants . All complications occurred before loading . Three complications were associated with the failure of the m and ibular grafts ( 15 % ) , determining the failures of 3 implants in one patient and 2 prostheses could not be delivered . One patient was re-grafted and 2 patients received short implants instead . Apart from those complications associated with graft failures , there were 4 perforations of the sinus membrane during sinus lifting and 7 temporary lower lip paraesthesiae lasting up to 4 days with no long-term consequences for the patients . All maxillary implants and prostheses were successful . All 20 patients treated with m and ibular implants and 15 patients treated with maxillary implants preferred short implants , whereas 5 patients treated with maxillary implants described both procedures as equally acceptable . These differences were statistically significant . CONCLUSIONS Short-term data ( 5 months after loading ) indicate that 6 mm-long implants with a conventional diameter of 4 mm achieved similar if not better results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation , especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity . However , 5- to 10-year post-loading data are necessary before making reliable recommendations PURPOSE To evaluate whether short ( 5 mm ) dental implants could be a suitable alternative to augmentation and placement of longer implants ( 10 mm ) in posterior atrophic jaws . MATERIAL S AND METHODS Thirty partially edentulous patients with bilateral posterior edentulism were included : 15 patients having 5 to 7 mm of residual crestal height above the m and ibular canal , and 15 patients having 4 to 6 mm of residual crestal height below the maxillary sinus and bone thickness of at least 8 mm measured on a CT scan . The patients were r and omised either to receive one to three submerged 5-mm-long Rescue implants ( Megagen ) or 10-mm-long implants placed in augmented bone according to a split-mouth design . M and ibles were augmented with interpositional anorganic bovine bone blocks ( Bio-Oss ) and maxillae with granular Bio-Oss placed through a lateral window under the lifted sinus membrane . Resorbable barriers were used to cover the grafted sites . Grafts were left to heal for 4 months before placing the implants using a submerged technique . Four months after implant placement , provisional reinforced acrylic prostheses were delivered and replaced 4 months later by definitive screw-retained metal-ceramic prostheses . Outcome measures were : prosthesis and implant failures , any complications , time needed to fully recover mental nerve function ( only for m and ibular implants ) and patient preference assessed 1 month after loading . All patients were followed up to delivery of the final restorations ( 4 months after loading ) . RESULTS A systematic deviation from the research protocol occurred : the operator used another implant system ( EZ Plus , Megagen ) for implants 10 mm or longer with a diameter of 4 mm at the augmented sites . No patients dropped out . In 5 patients of the augmented group ( all m and ibles ) , there was not enough height to place 10-mm-long implants as planned and shorter implants ( 7 and 8.5 mm ) were used instead . In each group , one prosthesis could not be placed when planned because an implant was found to be mobile at abutment connection : one 5 mm maxillary implant and one 8.5 mm m and ibular implant in the augmented group . Five complications occurred : two in the augmented group ( one maxillary sinus perforation and one m and ibular wound dehiscence after implant placement possibly associated with the failure of one implant ) versus three maxillary sinus perforations in the 5-mm-long implant group . The difference was not statistically significant . No patient suffered from permanent disruption of alveolar inferior nerve function , however , significantly more patients had paraesthesia for up to 3 days in the augmented group . There was no statistically significant difference in patient preference with the majority of patients expressing no preference for which treatment they received , finding both of them acceptable PURPOSE To evaluate whether 5 × 5 mm dental implants with a novel nanostructured calcium-incorporated titanium surface could be an alternative to at least 5 × 10 mm-long implants placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS Forty patients with atrophic posterior ( premolar and molar areas ) m and ibles having 5 to 7 mm of bone height above the m and ibular canal and 40 patients with atrophic maxillae having 4 to 6 mm below the maxillary sinus , were r and omised according to a parallel group design to receive one to three 5 × 5 mm implants or one to three at least 5 × 10 mm-long implants in augmented bone at two centres . M and ibles were vertically augmented with interpositional bovine bone blocks and resorbable barriers and implants were placed after 4 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window covered with resorbable barriers and implants were placed simultaneously . All implants were submerged and loaded after 4 months with provisional prostheses . Four months later , definitive screw-retained or provisionally cemented metal-ceramic or zirconia prostheses were delivered . Outcome measures were prosthesis and implant failures as well as any complication . RESULTS Patients were followed to 4 months post-loading with the exception of one patient who underwent m and ibular augmentation and had multiple complications at and after grafting , and subsequent graft failure , who did not want to go ahead with the treatment . This case was considered a complete failure . There were no statistically significant differences in prosthesis and implant failures . In m and ibles , apart from the complete graft failure , one 5 × 10 mm implant failed at placement of the provisional prosthesis . In maxillae , one 5 × 5 mm implant failed with its provisional crown 3 months after loading . All complications occurred before loading . Significantly more intra- and postoperative complications occurred at both m and ibular and maxillary grafted sites : 16 augmented patients were affected by complications versus 8 patients treated with short implants in the m and ible ( P = 0.022 ; difference in proportion = 0.40 ; CI 95 % 0.12 to 0.68 ) , and 5 sinus-lifted patients versus none treated with maxillary short implants ( P = 0.047 ; difference in proportion = 0.25 ; CI 95 % 0.06 to 0.44 ) . CONCLUSIONS Short-term data ( 4 months after loading ) indicate that 5 × 5 mm implants achieved similar results compared to longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity . However , 5 to 10 years of post-loading data are necessary before making reliable recommendations PURPOSE To evaluate whether short ( 5.0 to 8.5 mm ) dental implants could be a suitable alternative to longer ( at least 11.5 mm-long ) implants placed in atrophic maxillae augmented with autogenous bone for supporting dental prostheses . MATERIAL S AND METHODS Twenty-eight patients with fully edentulous atrophic maxillae , whom had 5 to 9 mm of residual crestal bone height which was at least 5 mm thick , measured using computerised tomography ( CT ) scans , were r and omised into two groups either to receive 4 to 8 short ( 5.0 to 8.5 mm ) implants ( 15 patients ) or autogenous bone from the iliac crest to allow the placement of at least 11.5 mm-long implants ( 13 patients ) . Bone blocks and the windows at the maxillary sinuses were covered with rigid resorbable barriers . Grafts were left to heal for 4 months before placing implants which were submerged . After 4 months , provisional reinforced acrylic prostheses or bar retained overdentures were delivered . Provisional prostheses were replaced , after 4 months , by definitive screw-retained metal-resin cross-arch restorations . Outcome measures were prosthesis and implant failures , any complications , peri-implant marginal bone level changes and patient satisfaction . Patients were followed up to 1 year after loading . RESULTS All patients were rehabilitated with implant-supported prostheses but two patients dropped out from the augmented group . One bilateral sinus lift procedure failed for infection , although short implants could be placed . One implant failed in the augmented group versus two short implants in two patients ( Fishers exact test P = 1.00 ; difference in proportions = 0.06 ; 95 % CI -0.28 to 0.17 ) . All failures occurred before loading . Significantly more complications occurred in augmented patients : eight complications occurred in 5 augmented patients ( all of them complained of pain 1 month after bone harvesting from the iliac crest ) versus no complications in the short implant ( Fisher 's exact test P = 0.013 ; difference in proportions = 0.38 ; 95 % CI 0.11 to 0.65 ) . Both groups presented a significant peri-implant marginal bone loss at 1 year after loading ( P < 0.0001 ) ; -1.05 ( 0.20 ) mm for short implants and -1.01 ( 0.16 ) mm for the augmented group , respectively , with no statistically significant differences between the two groups ( mean difference -0.04 mm ; 95 % CI -0.22 to 0.14 ; P = 0.59 ) . All patients were fully satisfied with the treatment and would have it again . CONCLUSIONS This pilot study suggests that short implants may be a suitable , cheaper and faster alternative to longer implants placed in bone augmented with autogenous bone for rehabilitating edentulous atrophic maxillae , however , these preliminary results need to be confirmed by larger trials with follow-ups of at least 5 years PURPOSE To evaluate whether 6 mm long × 4 mm wide dental implants could be an alternative to implants of at least 10 mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS A total of 20 patients with bilateral atrophic m and ibles , and 20 patients with bilateral atrophic maxillae , having 5 mm to 7 mm of bone height below the maxillary sinus or 6 mm to 8 mm above the m and ibular canal , had their side of the jaws r and omly allocated according to a split-mouth design . They were allocated to receive one to three 6 mm long × 4 mm wide implants , or implants of at least 10 mm long in augmented bone by two different surgeons at different centres . M and ibles were vertically augmented with interpositional equine bone blocks and resorbable barriers , and implants were placed 3 months later . Maxillary sinuses were augmented with particulated porcine bone via a lateral window and implants were placed simultaneously . After 4 months , all implants were submerged and loaded with provisional prostheses . Four months later , definitive prostheses were delivered . Outcome measures were prosthesis and implant failures , any complication and radiographic peri-implant marginal bone level changes . RESULTS Five patients ( three treated in m and ibles and two in maxillae ) dropped out before the 3-year post-loading follow-up . Two short maxillary implants affected by peri-implantitis failed together with their prosthesis vs three m and ibular prostheses that could not be placed on implants at least 10 mm long due to graft failures ; one was associated with the loss of three implants because of infection . There were no statistically significant differences in implant ( difference in proportions = 0.000 ; 95 % CI : -0.140 to 0.140 ; P = 1.000 ) and prosthesis failures ( difference in proportions = 0.057 ; 95 % CI : -0.094 to 0.216 ; P = 0.625 ) . In total , 18 complications occurred in 13 patients at augmented sites vs four complications in three patients with 6 mm long implants . Significantly more complications occurred at grafted sites in m and ibles ( difference in proportions = 0.353 ; 95 % CI : 0.005 to 0.616 ; P = 0.031 ) , but not in maxillae ( difference in proportions = 0.222 ; 95 % CI : -0.071 to 0.486 ; P = 0.219 ) . In m and ibles , patients with 6 mm long implants lost an average of 1.25 mm of peri-implant bone at 3 years vs 1.54 mm in patients with implants of at least 10 mm long . The difference was statistically significant ( mean difference = 0.29 mm ; 95 % CI : 0.08 to 0.51 mm ; P = 0.010 ) . In maxillas , patients with 6 mm-long implants lost an average of 1.28 mm of peri-implant bone at 3 years vs 1.50 mm in patients with implants of at least 10 mm long . The difference was statistically significant ( mean difference = 0.22 mm ; 95 % CI : 0.08 to 0.35 mm ; P = 0.003 ) . CONCLUSIONS Results at 3 years after loading indicate that 6 mm long implants with a conventional diameter of 4 mm achieved similar , if not better , results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation , especially in posterior m and ibles , since the treatment is faster , cheaper and associated with less morbidity . However , data obtained 5 to 10 years after loading are necessary before making reliable recommendations PURPOSE To evaluate whether 5-mm short dental implants could be an alternative to augmentation with anorganic bovine bone and placement of at least 10-mm long implants in posterior atrophic jaws . MATERIAL S AND METHODS Fifteen patients with bilateral atrophic m and ibles ( 5 mm to 7 mm bone height above the m and ibular canal ) and 15 patients with bilateral atrophic maxillae ( 4 mm to 6 mm bone height below the maxillary sinus ) , and bone thickness of at least 8 mm , were r and omised according to a split-mouth design to receive one to three 5-mm short implants or at least 10-mm long implants in augmented bone . M and ibles were vertically augmented with interpositional bone blocks and maxillary sinuses with particulated bone via a lateral window . Implants were placed after 4 months , submerged and loaded , after another 4 months , with provisional prostheses . Four months later , definitive provisionally cemented prostheses were delivered . Outcome measures were : prosthesis and implant failures ; any complication and peri-implant marginal bone level changes . RESULTS In five augmented m and ibles , the planned 10-mm long implants could not be placed and shorter implants ( 7 mm and 8.5 mm ) had to be used instead . Three years after loading , two patients , one treated in the m and ible and one in the maxilla , dropped out . Three prostheses ( 1 m and ibular and 2 maxillary ) failed in the short implant group versus none in the long implant group . In m and ibles , one long implant failed versus two short implants in 1 patient . In maxillae , one long implant failed versus three short implants in 2 patients . There were no statistically significant differences in the failures . Eight patients had 13 complications at short implants ( 1 patient accounted for 6 complications ) and 11 patients had 13 complications at long implants . There were no statistically significant differences in complications ( P = 0.63 , difference = 0.10 , 95 % CI from -0.22 to 0.42 ) . Three years after loading , patients with m and ibular implants lost on average 1.44 mm at short implants and 1.63 mm at long implants of peri-implant marginal bone . This difference was not statistically significant ( difference = 0.24 mm ; 95 % CI -0.01 , 0.49 P = 0.059 ) . In maxillae , patients lost on average 1.02 mm at short implants and 1.54 mm at long implants . This difference was statistically significant ( difference = 0.41 mm ; 95 % CI 0.21 , 0.60 , P = 0.001 ) . CONCLUSIONS Three years after loading , 5-mm short implants achieved similar results as longer implants in augmented bone . Short implants might be a preferable choice to vertical bone augmentation , especially in m and ibles , since the treatment is faster and cheaper , however there are still insufficient data on the long-term prognosis of short implants PURPOSE To evaluate whether 6.6-mm long implants could be a suitable alternative to longer implants placed in vertically augmented atrophic posterior m and ibles . MATERIAL S AND METHODS Sixty partially edentulous patients having 7 to 8 mm of residual crestal height and at least 5.5-mm thickness measured on computed tomography scans above the m and ibular canal were r and omly allocated according to a parallel-group design either to receive one to three submerged 6.6-mm long implants or 9.6-mm or longer implants ( 30 patients per group ) placed in vertically augmented bone . Bone was augmented with interpositional anorganic bovine bone blocks fixed with titanium plates and covered with resorbable barriers . Grafts were left to heal for 5 months before implant placement . Four months after implant placement , provisional acrylic prostheses were delivered , replaced , after 4 months , by definitive metal-ceramic prostheses . Outcome measures were : prosthesis and implant failures , complications , and radiographic peri-implant marginal bone level changes . Patients were followed up to 8 years after loading . RESULTS Eight years after loading 12 patients dropped out , five from the short implant group and seven from the augmented group . The augmentation procedure failed in two patients and only 6.6-mm long implants could be inserted . There were no statistically significant differences for prosthesis and implant failures . Four prostheses failed in three patients of the short implant group versus three prostheses in three patients of the augmented group ( Fisher exact test P = 1.000 ; difference in proportions = 0.01 ; 95 % CI : -0.19 to 0.22 ) . Five short implants failed in three patients versus three long implants in three patients ( Fisher exact test P = 1.000 ; difference in proportions = 0.01 ; 95 % CI : -0.19 to 0.22 ) . There were statistically more complications in augmented patients ( 27 complications in 22 augmented patients versus 9 complications in 8 patients of the short implant group ) ( Fisher exact test P < 0.001 ; difference in proportions = 0.64 ; 95 % CI : 0.38 to 0.79 ) . Both groups gradually lost peri-implant bone in a statistically significant way . Eight years after loading , short implant group patients lost an average of 1.58 mm of peri-implant bone compared with 2.46 mm in the augmented group . Short implants experienced statistically significantly less bone loss ( 0.88 mm , 95 % CI : 0.50 to 1.26 mm ) than long implants . CONCLUSIONS When residual bone height over the m and ibular canal is between 7 and 8 mm , 6.6-mm short implants are an interesting alternative to vertical augmentation in posterior atrophic m and ibles since the treatment is faster , cheaper and associated with less morbidity PURPOSE To evaluate whether 6-mm-long by 4-mm-wide dental implants could be an alternative to implants at least 10-mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS A total of 20 patients with bilateral atrophic m and ibles and 20 patients with bilateral atrophic maxillae , having 5 to 7 mm of bone height below the maxillary sinus or 6 to 8 mm above the m and ibular canal , had their sides of the jaws r and omly allocated according to a split-mouth design . They were allocated to receive one to three 6-mm-long and 4-mm-wide implants , or implants at least 10-mm long in augmented bone by two different surgeons in different centres . M and ibles were vertically augmented with interpositional equine bone blocks and resorbable barriers , and implants were placed 3 months later . Maxillary sinuses were augmented with particulated porcine bone via a lateral window and implants were placed simultaneously . All implants were submerged and loaded , after 4 months , with provisional prostheses . Four months later , definitive prostheses were delivered . Outcome measures were prosthesis and implant failures , any complication and radiographic peri-implant marginal bone level changes . The follow-up was 5 years after loading for all patients . RESULTS Eight patients ( five treated in m and ibles and three in maxillae ) dropped out before the 5-year post-loading follow-up . Four short implants ( two maxillary and two m and ibular ) affected by peri-implantitis failed together with their prostheses versus three m and ibular prostheses which could not be placed on implants at least 10-mm long due to graft failures ; one was associated with the loss of three implants because of infection . There were no statistically significant differences in implant ( P = 1.0 ) and prosthesis failures ( P = 1.0 ) . In total , 19 complications occurred in 14 patients at augmented sites versus five complications in four patients with 6-mm-long implants ( P = 0.118 ) . More complications occurred at grafted sites both in m and ibles ( P = 0.727 ) , and maxillae ( P = 0.063 ) , although the differences were not statistically significant . In m and ibles , patients with 6-mm-long implants lost an average of 1.34 ± 0.35 mm of peri-implant bone at 5 years versus 2.11 ± 0.59 mm in patients with implants at least 10-mm long . The difference was statistically significant ( mean difference = 0.77 ± 0.70 mm ; 95 % CI : 0.32 to 1.21 mm ; P = 0.003 ) . In maxillae , patients with 6-mm-long implants lost an average of 1.52 ± 0.47 mm of peri-implant bone at 5 years versus 1.85 ± 0.51 mm in patients with implants at least 10-mm long . The difference was statistically significant ( mean difference = 0.33 ± 0.36 mm ; 95 % CI : 0.14 to 0.53 mm ; P = 0.002 ) . CONCLUSIONS Results at 5 years after loading indicate that 6-mm-long implants with a conventional diameter of 4 mm achieved similar results to longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation , especially in posterior m and ibles since the treatment was faster , cheaper and associated with less morbidity . However , 10-year post-loading data are necessary before making reliable recommendations PURPOSE To evaluate whether 5 × 5 mm dental implants with a novel nanostructured calcium-incorporated titanium surface could be an alternative to implants at least 10-mm long placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS Forty patients with atrophic posterior ( premolar and molar areas ) m and ibles having 5- to 7-mm bone height above the m and ibular canal , and 40 patients with atrophic maxillae having 4- to 6-mm bone height below the maxillary sinus , were r and omised according to a parallel-group design to receive one to three 5-mm implants or one to three at least 10-mm long implants in augmented bone at two centres . All implants had a diameter of 5 mm . M and ibles were vertically augmented with interpositional bovine bone blocks covered with resorbable barriers . Implants were placed after 4 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window covered with resorbable barriers and implants were placed simultaneously . All implants were submerged and loaded after 4 months with provisional prostheses . Four months later , definitive screw-retained or provisionally cemented metal-ceramic or zirconia prostheses were delivered . Patients were followed to 5 years post-loading and the outcome measures were : prosthesis and implant failures , any complication and peri-implant marginal bone level changes . RESULTS Sixteen patients dropped out before the 5-year evaluation ( four short m and ibles , three short maxillae , six augmented m and ibles and three augmented maxillae ) . In m and ibles , two grafted patients were not prosthetically rehabilitated because of multiple complications , and three implants failed in the same patient ( one was a replacement implant ) versus one patient who lost his short implant and crown 2 years after loading . In maxillae one short implant failed with its provisional crown 3 months post-loading . There were no statistically significant differences in prostheses ( difference in proportion = -0.003 ; 95 % CI : -0.14 to 0.13 ; P = 1.000 ) and implant failures ( difference in proportion = -0.03 ; 95 % CI : -0.17 to 0.09 ; P = 0.609 ) up to 5 years after loading . Significantly more complications occurred at m and ibular grafted sites : 17 augmented patients were affected by complications versus nine patients treated with short implants in m and ibles ( difference in proportion = 0.39 ; 95 % CI : 0.10 to 0.62 ; P = 0.013 ) . In the maxilla seven sinus-elevated patients versus two patients treated with short implants were affected by complications , the difference not being statistically significant ( difference in proportion = 0.25 ; 95 % CI : -0.04 to 0.49 ; P = 0.128 ) . Patients with m and ibular short implants lost on average 1.22 mm of peri-implant bone at 5 years and patients with 10-mm or longer m and ibular implants lost 1.70 mm . Patients with maxillary short implants lost on average 1.25 mm of peri-implant bone at 5 years and patients with 10-mm or longer maxillary implants lost 1.73 mm . Longer implants showed a greater bone loss up to 5 years after loading than short implants both in maxillae ( mean difference : -0.48 mm ; 95 % CI : -0.89 to -0.07 mm ; P = 0.024 ) and in m and ibles ( mean difference : -0.48 mm ; 95 % CI : -0.79 to -0.18 mm ; P = 0.004 ) . CONCLUSIONS Five years after loading , 5 × 5 mm implants achieved similar results to longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity ; however , 10-year post-loading data are necessary before making reliable recommendations PURPOSE To evaluate whether 5-mm short dental implants could be an alternative to augmentation with anorganic bovine bone and placement of at least 10-mm long implants in posterior atrophic jaws . MATERIAL S AND METHODS Fifteen patients with bilateral atrophic m and ibles ( 5 to 7 mm bone height above the m and ibular canal ) and 15 patients with bilateral atrophic maxillae ( 4 to 6 mm bone height below the maxillary sinus ) , and bone thickness of at least 8 mm , were r and omised according to a split-mouth design to receive one to three 5-mm short implants or at least 10-mm long implants in augmented bone . M and ibles were vertically augmented with interpositional bone blocks and maxillary sinuses with particulated bone via a lateral window . Implants were placed after 4 months , submerged and loaded , after another 4 months , with provisional prostheses . Four months later , definitive provisionally cemented prostheses were delivered . Outcome measures were : prosthesis and implant failures , any complication and peri-implant marginal bone level changes . RESULTS In five augmented m and ibles the planned 10-mm long implants could not be placed and shorter implants ( 7.0 and 8.5 mm ) had to be used instead . Five years after loading , six patients , five treated in the m and ible and one in the maxilla , dropped out . Three prostheses ( one m and ibular and two maxillary ) failed in the short-implant group versus none in the long-implant group . In m and ibles one long implant failed versus two short implants in one patient . In maxillae one long implant failed versus three short implants in two patients . There were no statistically significant differences in implant ( n = 26 ; P = 1.00 , difference = 3.85 % , 95 % CI : -12.95 % to 20.64 % ) and prosthetic ( n = 26 ; P = 0.250 , difference = 11.54 % , 95 % CI : -0.74 % to 23.82 % ) failures . Eleven patients had 16 complications at short implants ( one patient accounted for six complications ) and 12 patients had 14 complications at long implants . There were no statistically significant differences in complications ( n = 28 ; P = 1.00 , difference = -3.57 % , 95 % CI : -30.65 % to 23.51 % ) . Five years after loading , patients with m and ibular implants lost on average 1.72 mm at short implants and 2.10 mm at long implants of peri-implant marginal bone . This difference was statistically significant ( difference = 0.37 ± 0.43 mm ; 95 % CI : 0.07 to 0.68 mm ; P = 0.022 ) . In maxillae , patients lost on average 1.31 mm at short implants and 1.79 mm at long implants . This difference was statistically significant ( difference = 0.48 ± 0.43 mm ; 95 % CI : 0.22 to 0.74 mm ; P = 0.002 ) . CONCLUSIONS Five years after loading , 5-mm short implants achieved similar results to longer implants in augmented bone . The choice of short implants might be preferable to vertical bone augmentation , especially in m and ibles , since the treatment is faster and cheaper |
534 | 31,588,598 | There was no statistical difference between nurse practitioner-led care and usual care for 30-day readmissions , health related quality of life and length of stay .
IMPACT Low to moderate quality evidence was identified with no statistically significant associated outcomes of care . | AIM To assess r and omized controlled trials evaluating the impact of nurse practitioner-led cardiovascular care .
BACKGROUND Systematic review of nurse practitioner led-care in patients with cardiovascular disease has not been completed . | Objective To investigate whether an internet based , nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinical ly manifest vascular disease . Design Prospect i ve r and omised controlled trial . Setting Multicentre trial in secondary and tertiary healthcare setting . Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary , cerebral , or peripheral arteries and with at least two treatable risk factors not at goal . Intervention Personalised website with an overview and actual status of patients ’ risk factors and mail communication via the website with a nurse practitioner for 12 months ; the intervention combined self management support , monitoring of disease control , and drug treatment . Main outcome measures The primary endpoint was the relative change in Framingham heart risk score after 1 year . Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor . Results Participants ’ mean age was 59.9 ( SD 8.4 ) years , and most patients ( n=246 ; 75 % ) were male . After 1 year , the relative change in Framingham heart risk score of the intervention group compared with the usual care group was −14 % ( 95 % confidence interval −25 % to −2 % ) . At baseline , the Framingham heart risk score was higher in the intervention group than in the usual care group ( 16.1 ( SD 10.6 ) v 14.0 ( 10.5 ) ) , so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score . This produced a relative change of −12 % ( −22 % to −3 % ) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and −8 % ( −18 % to 2 % ) adjusted for the baseline score . Of the individual risk factors , a difference between groups was observed in low density lipoprotein cholesterol ( −0.3 , −0.5 to −0.1 , mmol/L ) and smoking ( −7.7 % , −14.9 % to −0.4 % ) . Some other risk factors tended to improve ( body mass index , triglycerides , systolic blood pressure , renal function ) or tended to worsen ( glucose concentration , albuminuria ) . Conclusion An internet based , nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease . Trial registration Clinical trials NCT00785031 BACKGROUND This article is the result of a debate at the European Journal of Orthodontics Open Session in 2013 in Reykjavik , Icel and . OBJECTIVE The aim of this article is to highlight some of the strengths and weakness of clinical orthodontic research , with particular emphasis on r and omized controlled trials ( RCT ) . The ultimate aim of improving clinical orthodontic research in general . DESIGN This article is organized into two sections with arguments for and against RCTs . The background s to evidence -based evaluation and the level or quality of evidence in trials are discussed . The article emphasises what makes high quality clinical research , and gives practical advice including examples of tips and potential pitfalls for those undertaking clinical research . RESULTS AND CONCLUSION The overriding message is constructive and it is hoped that the article serves as an aid in evaluating , design ing , conducting , and reporting clinical research AIMS To describe and compare the outcomes of a nurse practitioner-managed cardiac surgery follow-up model of care with the st and ard model of primary care provider follow-up for coronary artery bypass graft surgery patients . BACKGROUND Advances in healthcare have had a favourable impact on length of stay following cardiac surgery ; however , the shorter length of stay has not been accompanied by enhanced support to bridge the gap between acute care and the community setting . DESIGN Prospect i ve ( 2009 - 2010 ) r and omized study . METHODS Elective cardiac surgery patients ( N = 200 ) were r and omly assigned to the nurse practitioner follow-up intervention or to the st and ard model of follow-up care . The main outcomes were health-related quality of life , patient satisfaction , symptoms , and health re source use . Outcome data were elicited via telephone interviews at 2 and 6 weeks postdischarge . RESULTS Baseline differences between the two groups were non-significant ; however , at 2 weeks postdischarge , the intervention group reported significantly fewer symptoms and higher physical functioning status . At 2 and 6 weeks postdischarge , the intervention group was significantly more satisfied with the amount of help , as well as the quality of the services received . Differences in healthcare re source use were not statistically significant . CONCLUSION This evidence suggests that the nurse practitioner-managed model of follow-up care effectively bridges the gap between institutional and primary care in the cardiac surgery population BACKGROUND High dem and for acute care nurse practitioners ( ACNPs ) in Canadian postoperative cardiac surgery setting s has outpaced method ologically rigorous research to support the role . PURPOSE To compare the effectiveness of ACNP-led care to hospitalist-led care in a postoperative cardiac surgery unit in a Canadian , university-affiliated , tertiary care hospital . METHODS Patients scheduled for urgent or elective coronary artery bypass and /or valvular surgery were r and omly assigned to either ACNP-led ( n=22 ) or hospitalist-led ( n=81 ) postoperative care . Both ACNPs and hospitalists worked in collaboration with a cardiac surgeon . Outcome variables included length of hospital stay , hospital readmission rate , postoperative complications , adherence to follow-up appointments , attendance at cardiac rehabilitation and both patient and health care team satisfaction . RESULTS Baseline demographic characteristics were similar between groups except more patients in the ACNP-led group had had surgery on an urgent basis ( p < or = 0.01 ) , and had undergone more complicated surgical procedures ( p < or = 0.01 ) . After discharge , more patients in the hospitalist-led group had visited their family doctor within a week ( p < or = 0.02 ) and measures of satisfaction relating to teaching , answering questions , listening and pain management were higher in the ACNP-led group . CONCLUSION / IMPLICATION S Although challenges in recruitment yielded a lower than anticipated sample size , this study contributes to our knowledge of the ACNP role in postoperative cardiac surgery . Our findings provide support for the ACNP role in this setting as patients who received care from an ACNP had similar outcomes to hospitalist-led care and reported greater satisfaction in some measures of care Objective To assess the cost-effectiveness of an internet-based , nurse-led vascular risk factor management programme in addition to usual care compared with usual care alone in patients with a clinical manifestation of a vascular disease . Design Cost-effectiveness analysis alongside a r and omised controlled trial ( the Internet-based vascular Risk factor Intervention and Self-management ( IRIS ) study ) . Setting Multicentre trial in a secondary and tertiary healthcare setting . Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary , cerebral , or peripheral arteries and with ≥2 treatable vascular risk factors not at goal . Intervention The intervention consisted of a personalised website with an overview and actual status of patients ’ vascular risk factors , and mail communication with a nurse practitioner via the website for 12 months . The intervention combined self-management support , monitoring of disease control and pharmacotherapy . Main outcome measures Societal costs , quality -adjusted life-years ( QALYs ) and incremental cost-effectiveness . Results Patients experienced equal health benefits , that is , 0.86 vs 0.85 QALY ( intervention vs usual care ) at 1 year . Adjusting for baseline differences , the incremental QALY difference was −0.014 ( 95 % CI −0.034 to 0.007 ) . The intervention was associated with lower total costs ( € 4859 vs € 5078 , difference € 219 , 95 % CI −€2301 to € 1825 ) . The probability that the intervention is cost-effective at a threshold value of € 20 000/QALY , is 65 % . At mean annual cost of € 220 per patient , the intervention is relatively cheap . Conclusions An internet-based , nurse-led intervention in addition to usual care to improve vascular risk factors in patients with a clinical manifestation of a vascular disease does not result in a QALY gain at 1 year , but has a small effect on vascular risk factors and is associated with lower costs . Trial registration number NCT00785031 This study reports results of the 2-year follow-up phase of a r and omized study comparing outcomes of patients assigned to a nurse practitioner or a physician primary care practice . In the sample of 406 adults , no differences were found between the groups in health status , disease-specific physiologic measures , satisfaction or use of specialist , emergency room or inpatient services . Physician patients averaged more primary care visits than nurse practitioner patients . The results are consistent with the 6-month findings and with a growing body of evidence that the quality of primary care delivered by nurse practitioners is equivalent to that by physicians Increasing dem and to deliver and document therapeutic and preventive care sharpens the need for disease management strategies that accomplish these goals efficiently while preserving quality of care . The purpose of this study was to compare selected outcomes for a new chronic disease management program involving a nurse practitioner - physician team with those of an existing model of care . One hundred fifty-seven patients with hypertension and diabetes mellitus were r and omly assigned to their primary care physician and a nurse practitioner or their primary care physician alone . Costs for personnel directly involved in patient management , calculated from hourly rates and encounter time with patients , and pre- and post- study glycosylated hemoglobin ( HbA1c ) , high-density lipoprotein cholesterol ( HDL-c ) , satisfaction with care and health-related quality of life ( HRQoL ) were assessed . Although 1-year costs for personnel were higher in the team-treated group , participants experienced significant improvements in mean HbA1c ( − 0.7 % , p = 0.02 ) and HDL-c ( + 2.6 mg dL − 1 , p = 0.02 ) . Additionally , satisfaction with care improved significantly for team-treated subjects in several sub-scales whereas the mean change over time in HRQoL did not differ significantly between groups . This study demonstrates the value of a complementary team approach to chronic disease management in improving patient-derived and clinical outcomes at modest incremental costs BACKGROUND Telemonitoring has been advocated as a way of decreasing costs and improving outcomes , but no study has looked at true Medicare payments and 30-day readmission rates in a r and omized group of well treated patients . OBJECTIVE The aim of this work was to analyze Medicare cl aims data to identify effects of home telemonitoring on medical costs , 30-day rehospitalization , mortality , and health-related quality of life . METHODS A total of 204 subjects were r and omized to usual-care and monitored groups and evaluated with the SF-36 and Minnesota Living With Heart Failure Question naire ( MLHF ) . Hospitalizations , Medicare payments , and mortality were also assessed . Monitored subjects transmitted weight , blood pressure , and heart rate , which were monitored by an experienced heart failure nurse practitioner . RESULTS Subjects were followed for 802 ± 430 days ; 75 subjects in the usual-care group ( 316 hospitalizations ) and 81 in the monitored group ( 327 hospitalizations ) were hospitalized at least once ( P = .51 ) . There were no differences in Medicare payments for inpatient or emergency department visits , and length of stay was not different between groups . There was no difference in 30-day readmissions ( P = .627 ) or mortality ( P = .575 ) . Scores for SF-36 and MLHF improved ( P < .001 ) over time , but there were no differences between groups . The percentage of patients readmitted within 30 days was lower with telemonitoring for the 1st year , but this did not persist . CONCLUSIONS Telemonitoring did not result in lower total costs , decreased hospitalizations , improved symptoms , or improved mortality . A decrease in 30-day readmission rates for the 1st year did not result in decreased total cost or better outcomes Low levels of statin adherence may compromise treatment outcomes . The aim of this study was to investigate whether nurse-led cardiovascular risk-factor counseling could improve statin adherence and lipid levels without increasing patients ' anxiety . Patients with indications for statin therapy for primary or secondary prevention of cardiovascular disease were r and omly assigned to receive routine care or extended care ( EC ) at baseline and at months 3 , 9 , and 18 . Patients in the EC group received a personalized risk-factor passport , showing modifiable and unmodifiable individual risk factors and a graphical presentation of their calculated absolute 10-year cardiovascular disease risk as well as the target risk that could be reached if all modifiable risk factors were optimally treated . Lipid levels were assessed at each visit . Carotid intima-media thickness was measured at baseline and at month 18 . Adherence , anxiety , quality of life , symptoms , and smoking status were assessed using a self-administered question naire at each visit . A total of 201 patients were included in the study . Statin adherence was significantly higher ( p < 0.01 ) and anxiety was significantly lower ( p < 0.01 ) in the EC group than in the routine care group . Low-density lipoprotein cholesterol was statistically significantly lower in the EC group than in the routine group ( 2.66 vs 3.00 mmol/L , respectively , p = 0.024 ) in primary prevention patients only . Intima-media thickness improved significantly from baseline ( p < 0.01 ) in all patients , irrespective of group assignment . In conclusion , cardiovascular risk-factor counseling result ed in improved lipid profiles in primary prevention patients and higher levels of adherence to statins and lower levels of anxiety in all patients Abstract From July , 1971 , to July , 1972 , in a large suburban Ontario practice of two family physicians , a r and omized controlled trial was conducted to assess the effects of substituting nurse practitioners for physicians in primary -care practice . Before and after the trial , the health status of patients who received conventional care from family physicians was compared with the status of those who received care mainly from nurse practitioners . Both groups of patients had a similar mortality experience , and no differences were found in physical functional capacity , social function or emotional function . The quality of care rendered to the two groups seemed similar , as assessed by a quantitative " indicator-condition " approach . Satisfaction was high among both patients and professional personnel . Although cost effective from society 's point of view , the new method of primary care was not financially profitable to doctors because of current restrictions on reimbursement for the nurse-practitioner services . ( N Background : A number of initiatives have employed nurses in roles traditionally associated with the medical profession but few have been evaluated in prospect i ve r and omised studies . This paper reports the results of a r and omised controlled trial to assess the performance of a nurse practitioner ( NP ) , trained to prepare patients for diagnostic cardiac catheterisation . Methods : Eligible and consenting patients were r and omised to preparation by either the NP or junior medical staff ( JMS ) . The safety outcome measure was the rate of in-hospital major adverse clinical events including death , myocardial infa rct ion and emergency bypass coronary surgery . Other outcome measures included rate of minor adverse events , cardiologist assessment of case preparation and presentation , patient satisfaction and duration of pre-admission clinic . Results : From April 1997 to May 1998 a series of 355 patients scheduled for elective , day-case , diagnostic cardiac catheterisation were screened . Of these , 345 patients were eligible for the study . A total of 339 patients consented to participate and were r and omised . Major adverse clinical events occurred in 0/175 ( 0 % ) patients in the NP group and 2/161 ( 1.2 % ) patients in the JMS group . ( Risk difference = —1.2 % , upper boundary of the 95 % confidence interval = ±2.0 % ) The cardiologist 's evaluation that the patient 's preparation was acceptable was high in both groups : NP group 98.3 % vs. JMS group 98.8 % : P=1.0 ) . Patient satisfaction , assessed by question naire , was greater in the NP group ( P = 0.04 ) . The median duration of the pre-admission clinic visit was lower in the NP group 165 min vs. 185 min in the JMS group , P = 0.01 ) This article discusses the history and development of r and omized clinical trial methodology , the reasons for its status and authority as a method of therapeutic evaluation , and the continuing role of clinical judgement in design ing , interpreting , and applying the findings of trials The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
535 | 20,091,554 | Larger effects of placebo were also found in trials that did not inform patients about the possible placebo intervention .
We did not find that placebo interventions have important clinical effects in general .
However , in certain setting s placebo interventions can influence patient-reported outcomes , especially pain and nausea , though it is difficult to distinguish patient-reported effects of placebo from biased reporting . | BACKGROUND Placebo interventions are often cl aim ed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions , but most reports on effects of placebos are based on studies that have not r and omised patients to placebo or no treatment .
Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinical ly important effects , but that there were possible beneficial effects on patient-reported outcomes , especially pain .
Since then several relevant trials have been published .
OBJECTIVES Our primary aims were to assess the effect of placebo interventions in general across all clinical conditions , and to investigate the effects of placebo interventions on specific clinical conditions .
Our secondary aims were to assess whether the effect of placebo treatments differed for patient-reported and observer-reported outcomes , and to explore other reasons for variations in effect . | Prevention of relapse following depression is a pressing research problem . The authors tested the efficacy of the tricyclic antidepressant amitriptyline and psychotherapy , alone and in combination , in preventing the relapse of 150 neurotic depressed female patients . They found that patients receiving amitriptyline and little psychotherapy had a 12-percent relapse rate , compared to a 16-percent rate for those receiving more psychotherapy and no medication . There was no significant difference between drug therapy alone or drug therapy in combination with psychotherapy . However , psychotherapy was beneficial to patients with problems of social adjustment and interpersonal relations . The need for further research and implication s for treatment are discussed A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) OBJECTIVE To investigate the effects of functional electrical stimulation ( FES ) on the improvement of motor and walking ability of the lower extremities of the patients with acute stroke . METHODS Forty-six patients with stroke ( including cerebral infa rct ion and hemorrhage ) , aged 71 + /- 8 ( 45 - 84 ) , hospitalized within 2 weeks ( 9 + /- 4 days ) after the onset , matched with one another in the baseline measurements before treatment , were assigned r and omly into 3 groups : FES group ( n = 13 ) , receiving st and ard rehabilitation combined with FES 30 minutes per day , 5 days per week for 3 weeks , placebo stimulation group ( n = 15 ) receiving st and ard rehabilitation combined with the installment of the FES apparatus , operated in the same manner as mentioned above , however , without real electric stimulation , and control group ( n = 13 ) , receiving st and ard rehabilitation alone . The score of the composite spasticity scale ( CSS ) was measured , electromyography was conducted to measure the maximum isometric voluntary contraction ( MIVC ) of the ankle dorsi-flexors and plantar-flexors , and walking ability by the test of timed " Up and Go " before treatment , weekly during the 3-week treatment , and 8 weeks after the onset of stroke . RESULTS After 3 weeks of treatment , the percentage of CSS score of the FES group was 31 % + /- 35 % , significantly lower than those of the placebo and control groups ( 50 % + /- 88 % and 65 % + /- 65 % respectively , both P < 0.05 ) ; the ankle dorsiflexion torque of MIVC of the FES group was 9 Nm + /- 5 Nm , significantly higher than those of the placebo and control groups ( 5 Nm + /- 3 Nm and 4 Nm + /- 5 Nm respectively , both P < 0.05 ) , and the electromyogram co-contraction ratio of the FES group was 8 % + /- 5 % , significantly lower than those of the placebo and control groups ( 27 % + /- 26 % and 28 % + /- 19 % respectively , both P < 0.05 ) . The time needed to recover the walking ability after the stroke onset of the FES group was 18 + /- 8 days , shorter by 2 approximately 3 days than those of the placebo and control groups ( 20 + /- 7 and 21 + /- 8 days respectively ) . The percentage of the patients able to walk with the help of a stick 3 weeks after treatment of the FES group was 85 % , significantly higher than those of the placebo and control groups ( 60 % and 46 % respectively , both P < 0.05 ) . 84.6 % of the patients of the FES group returned home , a percentage significantly higher than those of the placebo and control groups ( 53 % and 46 % respectively , both P < 0.05 ) . CONCLUSION FES , plus st and ard rehabilitation , is effective in improving the motor and walking ability of the patients with acute stroke , to the degree that most patients are recovered to be able to return home A prospect i ve , r and omized clinical trial was performed in order to assess the efficacy and side-effects of commonly used topical anaesthesia methods in adults receiving peripheral venous cannulation . The study was double-blinded to the degree that the method ologies allowed . One hundred and fifty healthy adults undergoing elective surgery were allocated at r and om to five groups : EMLA cream , ethyl chloride spray , intracutaneous infiltration with 2 % lidocaine , placebo cream and no treatment . Venipuncture was performed with a 18 G cannula on the dorsal side of the h and . Puncture pain and pain caused by the topical treatment itself were measured using a visual analogue scale ( VAS , range : 0 - 100 mm ) . Haemodynamic response , difficulties in performing the puncture and side-effects were recorded . All analgesic techniques were well tolerated . Haemodynamic response and degree of puncture difficulty showed no differences among the groups . Puncture pain ( median mrnVAS ) following infiltration ( 1.0 ) and EMLA ( 10.0 ) was significantly lower than no treatment ( 30.0 ) or placebo ( 30.0 ) . The benefit of local infiltration was altered by injection pain ( 11.5 ) . Spray did not significantly lower puncture pain ( 26.5 ) and , in addition , was associated with discomfort ( 10.5 ) . In adults , EMLA cream significantly reduces puncture pain and represents an acceptable alternate method for topical anaesthesia in venous cannulation . Local lidocaine infiltration is impaired by applicational pain , whereas spraying the puncture site with ethyl chloride has no analgesic benefit BACKGROUND To our knowledge , verum acupuncture has never been directly compared with sham acupuncture and guideline -based conventional therapy in patients with chronic low back pain . METHODS A patient- and observer-blinded r and omized controlled trial conducted in Germany involving 340 outpatient practice s , including 1162 patients aged 18 to 86 years ( mean + /- SD age , 50 + /- 15 years ) with a history of chronic low back pain for a mean of 8 years . Patients underwent ten 30-minute sessions , generally 2 sessions per week , of verum acupuncture ( n = 387 ) according to principles of traditional Chinese medicine ; sham acupuncture ( n = 387 ) consisting of superficial needling at nonacupuncture points ; or conventional therapy , a combination of drugs , physical therapy , and exercise ( n = 388 ) . Five additional sessions were offered to patients who had a partial response to treatment ( 10%-50 % reduction in pain intensity ) . Primary outcome was response after 6 months , defined as 33 % improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale question naire or 12 % improvement or better on the back-specific Hanover Functional Ability Question naire . Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement . RESULTS At 6 months , response rate was 47.6 % in the verum acupuncture group , 44.2 % in the sham acupuncture group , and 27.4 % in the conventional therapy group . Differences among groups were as follows : verum vs sham , 3.4 % ( 95 % confidence interval , -3.7 % to 10.3 % ; P = .39 ) ; verum vs conventional therapy , 20.2 % ( 95 % confidence interval , 13.4 % to 26.7 % ; P < .001 ) ; and sham vs conventional therapy , 16.8 % ( 95 % confidence interval , 10.1 % to 23.4 % ; P < .001 . CONCLUSIONS Low back pain improved after acupuncture treatment for at least 6 months . Effectiveness of acupuncture , either verum or sham , was almost twice that of conventional therapy Objective : To assess the efficacy of an orally administered antioxidant dietary supplement for managing marginal dry eye . Design : A prospect i ve , r and omised , placebo controlled trial with cross-over . Setting : Eye Clinic , Department of Vision Sciences , Glasgow Caledonian University . Subjects : Forty marginal dry eye sufferers composed of 30 females and 10 males ( median age 53 y ; range 38–69 y ) . Interventions : Baseline assessment s were made of tear volume sufficiency ( thread test ) , tear quality ( stability ) , ocular surface status ( conjunctival impression cytology ) and dry eye symptoms ( question naire ) . Each subject was administered courses of active treatment , placebo and no treatment , in r and om order for 1 month each and results compared to baseline . Results : Tear stability and ocular surface status were significantly improved following active treatment ( P<0.05 ) . No changes from baseline were detected following administration of placebo and no treatment ( P>0.05 ) . Absolute increase in tear stability correlated with absolute change in goblet cell population density . Tear volume was not improved following any treatment period and dry eye symptom responses were subject to placebo effect . Conclusions : Oral antioxidants improved both tear stability and conjunctival health , although it is not yet understood whether increased ocular surface health mediates increased tear stability or vice versa . Sponsors : This study was supported by a PhD scholarship funded by the Department of Vision Sciences , Glasgow Caledonian University , Scotl and . Antioxidant supplements and placebos were kindly donated by Vitabiotics . European Journal of Clinical Nutrition ( 2001 ) 55 , Background and Purpose — The effectiveness of functional electrical stimulation ( FES ) has been investigated in chronic hemiplegia . The present study examines whether FES , given during acute stroke , was more effective in promoting motor recovery of the lower extremity and walking ability than st and ard rehabilitation alone . Methods — Forty-six subjects , 70.9±8.0 years old and 9.2±4.1 days after stroke , were assigned r and omly to 1 of 3 groups receiving st and ard rehabilitation with FES or placebo stimulation or alone ( control ) . FES was applied 30 minutes and placebo stimulation 60 minutes , 5 days per week for 3 weeks . Outcome measurements included composite spasticity score , maximum isometric voluntary contraction of ankle dorsi-flexors and planter-flexors , and walking ability . They were recorded before treatment , weekly during the 3-week treatment , and at week 8 after stroke . Results — No significant differences were found in the baseline measurements . After 3 weeks of treatment , there was a significant reduction in the percentage of composite spasticity score , and a significant improvement in the ankle dorsiflexion torque , accompanied by an increase in agonist electromyogram and a reduction in electromyogram cocontraction ratio in the FES group , when compared with the other 2 groups ( P<0.05 ) . All subjects in the FES group were able to walk after treatment , and 84.6 % of them returned home , in comparison with the placebo ( 53.3 % ) and control ( 46.2 % , P<0.05 ) groups . Conclusions — Fifteen sessions of FES , applied to subjects with acute stroke plus st and ard rehabilitation , improved their motor and walking ability to the degree that more subjects were able to return to home Auricular acupuncture can be an effective treatment for acute anxiety , but there is a lack of direct comparisons of acupuncture to proven st and ard drug treatments . In this study we compared the efficacy of auricular acupuncture with intranasal midazolam , placebo acupuncture , and no treatment for reducing dental anxiety . Patients having dental extraction s ( n = 67 ) were r and omized to ( i ) auricular acupuncture , ( ii ) placebo acupuncture , and ( iii ) intranasal midazolam and compared with a no treatment group . Anxiety was assessed before the interventions , at 30 min , and after the dental extraction . Physiological variables were assessed continuously . With the no treatment group as control , the auricular acupuncture group , and the midazolam group were significantly less anxious at 30 min as compared with patients in the placebo acupuncture group ( Spielberger Stait-Trait Anxiety Inventory X1 , P = 0.012 and < 0.001 , respectively ) . In addition , patient compliance assessed by the dentist was significantly improved if auricular acupuncture or application of intranasal midazolam had been performed ( P = 0.032 and 0.049 , respectively ) . In conclusion , both , auricular acupuncture and intranasal midazolam were similarly effective for the treatment of dental anxiety Meditation training appears to be a promising psychological approach to the control of hypertension . However , most studies to date have had serious deficiencies . This study attempted to correct many of these deficiencies . Forty-one unmedicated hypertensives referred by general practitioners were r and omly allocated to three groups . The treatment group ( SRELAX ) underwent training procedures based on Transcendental Meditation ; a placebo control group ( NSRELAX ) underwent identical training but without a mantra . Both procedures were compared with a no-treatment control group . The results showed modest reductions in blood pressure in both SRELAX and NSRELAX groups , compared with the no-treatment controls , with diastolic percentage reductions reaching significance ( p<0.05 ) . There was considerable subject variation in response , with overall a mean decline in diastolic blood pressure of 8–10 % on 3-month follow-up . Possible indicators to predict the response of subjects are considered and reasons for the similarity in the effectiveness of the SRELAX and NSRELAX conditions are discussed & NA ; In the present study , we examined the effects of preoperative electroacupuncture ( EA ) at classical bilateral acupuncture points ( Zusanli , also known as ST‐36 ) on postoperative pain and opioid‐related side effects . One hundred healthy consenting women undergoing lower abdominal surgery were r and omly assigned to four treatment regimens : Group I ( n=25 ) , control ; Group II ( n=25 ) , sham‐EA ( needle insertion without electrical stimulation ) ; Group III ( n=25 ) , low‐EA ( 2 Hz of electrical stimulation ) ; and Group IV ( n=25 ) , high‐EA ( 100 Hz of electrical stimulation ) . EA groups received needle insertion with or without electrical stimulation 20 min prior to anesthesia . All patients received patient‐controlled analgesia ( PCA ) of morphine postoperation . Postoperative pain was evaluated by recording ( 1 ) the time of the first required analgesic , ( 2 ) the number of PCA dem and s , ( 3 ) the total amount of morphine required by PCA , and ( 4 ) patients ' VAS pain score . We found that the time of first analgesic requested was 10 , 18 , 28 , and 28 min in the control , sham‐ , low‐ , and high‐EA groups , respectively . During the first 24 h , the total amount of morphine required was decreased by 21 , 43 and 61 % in the sham‐ , low‐ and high‐EA groups , respectively . The incidence of nausea and dizziness during the first 24 h after surgery was significantly reduced in both the low‐EA and high‐EA groups compared with the control and sham‐EA groups . We also found that sham‐EA exerts a beneficial effect with respect to its pain relieving quality but not the side effect profiles . Our findings demonstrates that preoperative treatment with low‐EA and high‐EA can reduce postoperative analgesic requirements and associated side effects in patients undergoing lower abdominal surgery Twenty‐seven long‐term psychiatric in patients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a r and omized double‐blind within‐subjects design . The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication , when taking placebo and when taking no antiparkinsonian drug . The relapse rate on no medication was 14 % , and if patients relapsed on no medication they also relapsed on placebo . The relapse rate was not significantly different on active medication . Nor were there significant differences in ratings of parkinsonism or dyskinesia . The lack of difference between double‐blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors , as significant unblinding may occur in clinical trials SUMMARY The decline in blood pressure ( BP ) in essential hypertensives following hospitalization may result from : 1 ) regression toward the mean ; 2 ) reduction of anxiety as patients habituate to a new enrironment ; 3 ) the placebo effect of medication ; and 4 ) an independent effect of hospitalization itself . A r and omized crossover study of 12 essential hypertensives demonstrated a fall in supine blood pressure from 165.0/97.9 ± 2.3/1.1 mm Hg to 154.3/89.6 ± 2.7/1.1 mm Hg ( p < 0.005 ) due to hospitalization . A similar reduction in BP from 164.9/99.5 ± 8.4/4.1 mm Hg to 151.9/93.4 ± 4.5/1.9 mm Hg ( p < 0.005 ) result ed from regression toward the mean and habituatlon during the study period . Urinary catecholamines fell from 68.7 ± 5.0 to 55.1 ± 4.3 Mg/g creatinine/24 hours ( p < 0.05 ) due to hospitalization and from 56.1 ± 5.4 to 49.7 ± 43 fig/g creatinine/24 hours ( p < 0.05 ) with time . Although placebo therapy tended to reduce BP , it failed to do so significantly . When expressed as a percentage of the individual 's overall mean , urinary catecholamine excretion fell from 110.5 % ± 3.7 % to 89.5 % ± 3.7 % ( p < 0.001 ) during hospitalization and from 105.8 % ± 3.9 % to 94.2 % ± 3.9 % ( p < 0.05 ) during the outpatient period . Blood pressure and sympathetic activity rapidly returned to prehospitalization values on discharge . These factors may confound the analysis of drug effects on BP and sympathetic activity in essential hypertensives following admission to hospital Sixty-six tension headache patients were r and omly assigned to one of four conditions for 8 weeks : ( a ) progressive muscle relaxation ( PMR ) alone ; ( b ) PMR plus cognitive therapy ( PMR + Cog ) ; ( c ) pseudomeditation , a credible attention-placebo control ; or ( d ) continued headache monitoring . A comparison of overall headache activity ( headache index ) , derived from a daily headache diary , for 4 weeks before treatment to 4 weeks after treatment , revealed that active treatment ( PMR and PMR + Cog ) was superior to either control condition . Moreover , level of headache medication consumption decreased significantly for the active treatment groups . Although headache-index comparisons of the two active treatments showed no advantage for adding cognitive therapy to PMR , a measure of clinical ly significant change showed a trend for PMR + Cog to be superior to PMR alone Abstract A controlled trial was undertaken to compare the efficacy of transcutaneous electrical nerve stimulation ( TENS ) with st and ard intramuscular opiate analgesia in the management of postoperative pain following appendicectomy . Consecutive patients undergoing emergency appendicectomy were r and omised into control , sham TENS and active TENS groups . There was a significant decrease in pain severity and analgesic intake in both active and sham TENS groups when compared with the control group ( P less than 0.01 ) . No difference was demonstrated in pain severity between active and sham TENS groups but the active TENS group required slightly less analgesia . These results suggest that the major benefit of TENS in the postappendicectomy patient is due to its ' placebo effect ' and its use in this situation can not be recommended Four series of duodenal ulcer patients presenting with pain have been treated with two types of placebos ( intramuscular injections or tablets ) by 4 different physicians while a fifth group of patients did not receive any treatment . Patients noted the number of days with pain since the beginning of the test by themselves . All patients treated with placebo presented with a significantly shorter duration of pain than untreated patients . There was a significant difference between the actions of the different physicians on the duration of pain . This suggests that some , until now unprecised , character(s ) of the physician plays an important part in the relief of duodenal ulcer pain A prospect i ve , r and omized , controlled study was carried out to investigate the dilating and softening effect on the cervix of prostagl and in F2-alpha gel administered intracervically and of prostagl and in E2 tablets administered orally . A total of 581 patients were included in the study : 149 received 2.5 mg prostagl and in F2-alpha in gel form intracervically , 150 received 1 mg prostagl and in E2 in tablet form orally , 138 were given placebo gel and 144 no medication at all . In the group given prostagl and in F2-alpha gel intracervically , success was achieved in 85.8 % of patients and partial success in 8.8 % . In the group given prostagl and in E2 tablets orally , the results were successful in 29.4 % and partially successful in 40.6 % . The incidence of side effects in the group given prostagl and in F2-alpha gel was rather high - 53 % . The results show that prostagl and in can bring about a certain softening of the cervix , but side effects can not be ruled out . Nevertheless , priming of the cervix is to be recommended in young primigravidas A prospect i ve , double-blind study was carried out to assess the efficacy of interferon alfa-2b , with or without pre-treatment prednisone withdrawal , in patients with chronic hepatitis B. A total of 57 Belgian and Dutch patients were included in the study . Patients were divided into four treatment groups : Group A , prednisone withdrawal followed by interferon 5 million units per day ; Groups B and C , placebo followed by interferon 5 or 1 million units , respectively ; and Group D , untreated controls followed for 1 year . All treated patients received interferon for 16 weeks . Two of the 14 control patients lost hepatitis B e antigen during the year of study , and only one of 15 patients in the interferon 1 million units group . Among the 28 patients receiving 5 million units of interferon ( with or without prednisone withdrawal ) , ten ( 36 % ) cleared hepatitis B e antigen during the study or within 6 months of the end of therapy . This was associated with a marked improvement in serum transaminase levels . When comparing Groups A and B , it was found that prednisone withdrawal therapy enhanced the response to interferon in patients with pre-treatment serum alanine aminotransferase levels below 100 IU/l , bringing the seroconversion rate up to 50 % , compared to 17 % on interferon alone . This effect was not seen in patients with high pre-treatment transaminase levels . All treatment responders showed a marked improvement in Knodell index score , whereas in the 15 non-responders from groups A and B , overall inflammatory activity remained the same in six , improved in five and worsened in four . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To determine the feasibility , in terms of acceptability to patients , physicians and other staff ; data return and statistical power of a study to eluci date the relative contributions of specific and non-specific effects in homeopathic treatment of dermatitis . DESIGN R and omised , controlled 4-arm trial , 2 arms double-blind . SETTING Outpatient clinic , Royal London Homoeopathic Hospital . PARTICIPANTS Seventy-five adult patients with dermatitis . INTERVENTIONS Patients were r and omly allocated to : ' fast track ' open verum homeopathy , ' fast track ' double-blind verum homeopathy , ' fast track ' double-blind placebo homeopathy or waiting list control . MAIN OUTCOME MEASURES One hundred millimeter visual analogue scale of overall symptom severity ; 10 point digital scores of sleep , itching , skin condition ; weekly 5-point Likert scale of topical steroid use ; Dermatology Life Quality Index at entry and completion . RESULTS Recruitment was below target , but the study was acceptable to staff and feasible . Blinded patients were more likely to withdraw ( P=0.021 , chi2 test ) . After correction for baseline differences and multiple comparisons , no outcome measure showed statistically significant between group differences . Blindness appeared to have a negative effect , but this was confounded by differential withdrawal . CONCLUSIONS A definitive trial of this design is unlikely to discriminate the relative contributions of the non-specific and specific effects to the outcome of homeopathic treatment of dermatitis , because of patient preference issues Studies in smoking cessation have generally failed to adequately control for active treatment effects and have assumed that measures of smoking behaviour ( i.e. , estimated smoking rate , self-monitoring and chemical analysis ) are equally reliable measures . Sixty smokers were r and omly assigned to one of four different smoking cessation treatment groups : hypnosis , focussed smoking , attention placebo and a waiting list control . Subjects were asked to estimate and monitor their own smoking behaviour . Blood sample s were also taken for thiocyanate analysis before treatment . Smoking rates were similarly measured directly , at 3 months and 6 months after treatment . The results indicate that the three measures of smoking behaviour were all highly correlated . No significant differences were found between treatments , directly after treatment or at the 3- and 6-month follow-ups . These results suggest that active treatment effects may not be responsible for behavioural change in a smoking cessation program . The implication s of these findings are discussed Five percent Amlexanox oral paste is a novel treatment for aphthous ulcers . In 3 controlled clinical studies that evaluated 1,124 immunocompetent patients with mild to moderate aphthous ulcers , 5 % Amlexanox oral paste ( Aphthasol ) was shown to accelerate healing of these ulcers . Treatment with Aphthasol reduced the median time to ulcer healing and to complete pain resolution in a statistically significant manner . This was true both when treatment with 5 % Amlexanox oral paste was compared to treatment with a vehicle and when treatment with the Amlexanox paste was compared to no treatment . Study results after 3 days comparing treatment with the paste and no treatment indicated complete healing of ulcers for 21 % and 8 % of patients , respectively . Complete resolution of pain after 3 days was reported for 44 % and 20 % of patients , respectively Study Design . Three-group , r and omized , single blinded , controlled trial . Objective . To test the effectiveness of physiotherapy-based rehabilitation starting 1 week after lumbar disc surgery . In addition , we tried to estimate the contribution of specific effects to the observed outcome ( efficacy ) . Summary of Background Data . Physiotherapy-based rehabilitation is usually recommended for patients following lumbar disc surgery . Few and conflicting data exist for the relative effectiveness of this intervention . Methods . A total of 120 patients following first-time , uncomplicated lumbar disc surgery were r and omly assigned to “ comprehensive ” physiotherapy , “ sham ” neck massage , or no therapy . Before enrollment , all subjects completed a minimal physiotherapeutic intervention . Physiotherapy was administered by experienced physiotherapists and consisted of 20 sessions per patient over 12 weeks . Masseurs administered “ sham massage ” to the neck . The amount of treatment time was equal to that of physiotherapy . The main outcome measure was the Low Back Pain Rating Score ( LBPRS ) at 6 and 12 weeks , and 1.5 years after r and omization . Secondary parameters were patients ' overall satisfaction with treatment outcome and socioeconomic and psychologic measures . Results . At the end of therapy ( 12 weeks ) , the LBPRS revealed a significantly better improvement in the physiotherapy group than in the untreated group . LBPRS outcome , however , did not significantly differ between physiotherapy and “ sham ” therapy . There was a tendency toward significance between the sham therapy and no therapy . Within the 1.5-year follow-up , LBP rating scales remained significantly improved compared with baseline , but there were no significant outcome differences . No statistically significant between-group differences were found for the secondary outcome parameters . Conclusion . As compared with no therapy , physiotherapy following first-time disc herniation operation is effective in the short-term . Because of the limited benefits of physiotherapy relative to “ sham ” therapy , it is open to question whether this treatment acts primarily physiologically in patients following first-time lumbar disc surgery , but psychological factors may contribute substantially to the benefits observed BACKGROUND Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness . We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with osteoarthritis of the knee . METHODS Patients with chronic osteoarthritis of the knee ( Kellgren grade < or = 2 ) were r and omly assigned to acupuncture ( n=150 ) , minimal acupuncture ( superficial needling at non-acupuncture points ; n=76 ) , or a waiting list control ( n=74 ) . Specialised physicians , in 28 outpatient centres , administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks . Patients completed st and ard question naires at baseline and after 8 weeks , 26 weeks , and 52 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index at the end of week 8 ( adjusted for baseline score ) . All main analyses were by intention to treat . RESULTS 294 patients were enrolled from March 6 , 2002 , to January 17 , 2003 ; eight patients were lost to follow-up after r and omisation , but were included in the final analysis . The mean baseline-adjusted WOMAC index at week 8 was 26.9 ( SE 1.4 ) in the acupuncture group , 35.8 ( 1.9 ) in the minimal acupuncture group , and 49.6 ( 2.0 ) in the waiting list group ( treatment difference acupuncture vs minimal acupuncture -8.8 , [ 95 % CI -13.5 to -4.2 ] , p=0.0002 ; acupuncture vs waiting list -22.7 [ -27.5 to -17.9 ] , p<0.0001 ) . After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant ( p=0.08 ) . INTERPRETATION After 8 weeks of treatment , pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee . However , this benefit decreases over time Study Design A r and omized , placebo-controlled trial in which patients received either usual care by a general practitioner ( information and analgesics ) , or placebo physiotherapy given by a physiotherapist , or exercise therapy given by a physiotherapist . Objective To assess the efficacy of exercise therapy on sickness absence from work in patients with acute low back pain . Summary of Background Data Exercise therapy during the nonchronic phase of back pain is considered to reduce sickness absence , but this opinion is controversiel . Methods Patients with acute nonspecific low back pain and a paid job were included for analysis . Sickness absence ( number of days ) was checked monthly during the 1-year follow-up period and compliance was also assessed . Results From 40 general practice s 363 patients who were gainfully employed were included . In the exercise therapy group the percentage of patients with sickness absence was higher and the duration of absence was longer than in the placebo and usual care groups , but these differences were not significant . Indications of more absence in the exercise therapy group appeared to be based largely on a greater number of patients with absences during the first 3 months . Patients in the exercise group who had not reported sick at entry had more sickness absences during the follow-up year than patients in the usual care and placebo group . Good compliance did not affect the results . Conclusions Exercise therapy for patients with acute low back pain does not reduce sickness absence & NA ; Post‐herpetic neuralgia ( PHN ) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly . Topical local anesthetics have shown promise in both uncontrolled and controlled studies . Thirty‐five subjects with established PHN affecting the torso or extremities completed a four‐session , r and om order , double‐blind , vehicle‐controlled study of the analgesic effects of topically applied 5 % lidocaine in the form of a non‐woven polyethylene adhesive patch . All subjects had allodynia on examination . Up to 3 patches , covering a maximum of 420 cm2 , were applied to cover the area of greatest pain as fully as possible . Lidocaine containing patches were applied in two of the four 12‐h‐long sessions , in one session vehicle patches were applied , and one session was a no‐treatment observation session . Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no‐treatment observation , and at all time points 4–12 h compared to vehicle patches . Lidocaine patches were superior to both no‐treatment observation and vehicle patches in averaged category pain relief scores . The highest blood Lidocaine level measured was 0.1 & mgr;g/ ml , indicating minimal systemic absorption of Lidocaine . Patch application was without systemic side effects and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5 % Lidocaine in patch form is easy to use and relieves post‐herpetic neuralgia The roots of essential hypertension extend back into the first two decades of life , suggesting that effective intervention during those years may lead to a reduction in the incidence of adult hypertension . Decreasing the dietary sodium/potassium ratio offers a potentially effective approach to blood pressure reduction . This study tested the feasibility of 3-year sodium reduction or potassium supplementation in adolescents and the effect of these interventions on the rate of rise of blood pressure during adolescence . After 19,452 5th to 8th grade students were screened , 210 from the upper 15 percentiles of blood pressure distribution ( 105 boys , 105 girls ) were r and omly assigned to one of three groups : low sodium diet ( 70 mmol sodium intake per day ) , potassium chloride supplementation ( normal diet plus 1 mmol/kg potassium chloride per day ) , or placebo ( normal diet plus placebo capsule ) . Capsules for the potassium chloride and placebo groups were administered in a double blind protocol . Blood pressure was measured every 3 months for 3 years . The effect of the intervention was determined by comparing the rate of rise ( slope ) of blood pressure among the groups using a r and om-coefficient growth curve model . The boys groups and the girls placebo group had similar positive blood pressure slopes that were significantly different from zero . The girls low sodium group had a slightly negative slope ( significantly lower than the slope of the girls placebo group ) , and the girls potassium group had a slightly positive slope . Both of these slopes were not significantly different from zero and were significantly lower than the slopes of the respective boys groups . ( ABSTRACT TRUNCATED AT 250 WORDS Background : The objectives were to determine whether a eutectic mixture of local anesthetic ( EMLA ) or placebo cream reduces pain during extracorporeal piezoelectric shock wave lithotripsy ( EPSWL ) , and to determine which of the components of the application ( i.e. , the occlusive dressing , the cream , or the local anesthetic ) contributes to analgesia . Methods : A r and omized , double blind , crossover study ( part 1 ) was performed in 12 patients who were scheduled for EPSWL procedures on an ambulatory basis who received the first treatment without any intervention and who had verbal pain scores of 70 or more ( on a 0-to-100 scale ) . For the next two treatments at 2-week intervals , patients were r and omly assigned to receive either 10 g EMLA or 10 g placebo cream and then crossed over to receive the other . The cream and occlusive dressing were left in place and immersed in water throughout the procedure . Verbal numeric pain score was assessed at 5 min after receiving the maximal tolerable intensity of shock wave and at the end of the procedure . The study continued ( part 2 ) in 202 ambulatory patients ; 125 men and 77 women , American Society of Anesthesiologists physical status I and II , subjected to EPSWL were r and omly allocated into five groups who received ( 1 ) nothing on the skin ( control ) , ( 2 ) plastic occlusive dressing , ( 3 ) placebo cream and plastic occlusive dressing , ( 4 ) EMLA cream and plastic occlusive dressing , ( 5 ) EMLA cream and plastic occlusive dressing for 60 min to achieve cutaneous anesthesia , which was removed before EPSWL . Pain score was evaluated 10 min into the procedure and at the end of the procedure . Result : Both parts of the study showed that patients who received either EMLA or placebo cream with dressing throughout the procedure experienced less pain and tolerated higher energy levels compared with the control . Patients who received only pre-EPSWL cutaneous anesthesia of EMLA and who received only the occlusive dressing did not have a reduction in pain score . Conclusions : EMLA and placebo creams under occlusive dressing reduced pain during EPSWL . The presence of the cream itself as a coupling medium contributed to analgesia . This may be a useful , simple , safe , and economical adjuvant technique to reduce pain during immersion EPSWL The suppression of S. mutans is a predominate factor in preventing tooth decay . Sustained-release-delivery varnish of chlorhexidine was applied to dental plastic shells and administered to eight volunteers to be worn while sleeping . Salivary bacterial sample s were taken on days 0 , 7 , 14 , 21 , 28 , 35 . A statistically significant reduction in S. mutans counts was recorded during the course of the study while a non-significant reduction in the total bacterial counts was found . Our results indicate that the application of chlorhexidine in the form of slow-release varnish in plastic shells is an effective intraoral drug delivery system result ing in reduction of S. mutans In a diabetes detection survey carried out between 1962 and 1965 , 2477 ( 1.1 % ) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal . Of these 2477 , 578 displayed impaired tolerance to oral glucose without having manifest diabetes . From this group , 267 men were divided into five groups and subjected to the following treatments and controls : ( a ) diet regulation and 0.5 g tolbutamide t.i.d . ( N = 49 ) , annual oral glucose tolerance test ( OGTT ) ; ( b ) diet regulation and one placebo tablet t.i.d . ( N = 48 ) , annual OGTT ; ( c ) diet regulation only ( N = 50 ) , annual OGTT ; ( d ) no treatment ( N = 61 ) , annual OGTT ; and ( e ) no treatment , OGTT at follow-up ( N = 59 at follow-up ) . In addition , a control group was included comprised of men with normal OGTT ( N = 52 ) . At follow-up , 29 % of those without diet regulation and medication ( group e ; N = 59 ) had developed diabetes . Of those on diet regulation , but without active medication ( group b plus group c , N = 98 ) , 13 % had diabetes . No individual maintaining tolbutamide and diet regulation ( N = 23 ) had progressed to diabetes . In this group , 80 % of those later examined ( N = 11 ) had serum tolbutamide concentrations in the therapeutic range . No individual with initially normal OGTT developed diabetes or impaired OGTT . The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes , whereas impaired glucose tolerance is associated with a high risk of progression to diabetes . In addition , it seems possible that treatment with diet regulation , in combination with tolbutamide , may prevent or postpone progression from impaired glucose tolerance to manifest diabetes The present study evaluated the efficacy of olfactory aversion conditioning in the management of overeating problems . 42 overweight female subjects were assigned to one of three treatment conditions : olfactory aversion therapy , attention placebo control , and no-contact control . One experimenter administered the 8-wk . treatment phase . The aversion therapy procedure entailed the pairing of selected target foods ( CSs ) with noxious odors ( UCSs ) . There were 25 pairings of the CS and UCSs during each weekly session . Four noxious odors were employed , one each week , to prevent habituation to the UCS . The attention-placebo control procedure was identical except that “ air ” was substituted for the putative UCS of the aversion therapy condition . At the end of the treatment period the aversion therapy group had lost 4.7 lb . ; the attention placebo controls had lost 3.6 lb . and the no-contact controls 0.5 lb . The difference between the aversion therapy group and the no-contact controls was significant and that between the attention placebo group and the no-contact controls approached significance . At a follow-up 8 wk . after the end of the treatment period the weights of all groups had risen to pretreatment levels and there were no differences between them . These results indicate that olfactory aversion therapy is not an efficient technique in promoting weight-loss OBJECTIVE Our purpose was to investigate the efficacy of P6 acupressure in reducing or relieving symptoms of nausea with or without vomiting and retching during pregnancy . STUDY DESIGN Symptomatic pregnant volunteers ( n=161 ) participated in a 7-day community-based clinical trial . All participants were assigned to one of three groups ( i.e. , P6 acupressure , placebo [ acupressure b and s inappropriately placed ] , or control ) on the basis of a process of blocked r and omization . Data were analyzed by error bar charts and analysis of variance of difference scores . RESULTS Of 161 women , 149 ( 92.5 % ) completed the protocol . Irrespective of group assignment , participants reported significant decreases in nausea ( p<0.0009 ) and vomiting or retching ( p<0.0009 ) . However , there was no differential treatment effect as a result of acupressure . CONCLUSION There was no apparent medical benefit from the use of P6 acupressure . Our findings differ from other recently published studies that did not include a control group Early childhood experiences with painful injections may lead to anxiety and fear . These reactions need not develop if steps are taken to reduce the pain associated with injections . The purpose of this study was to assess the efficacy of a refrigerant topical anesthetic in reducing injection pain in preschool children experiencing routine diphtheria-pertussis-tetanus ( DPT ) immunizations . This double-blind placebo-controlled study was conducted in community health clinics in conjunction with ongoing immunization programs . Ninety subjects , aged 4 - 5.5 years , were r and omly assigned to one of three groups : ( a ) refrigerant topical anesthetic ; ( b ) placebo topical spray ; and ( c ) no-spray control . Pain was measured subjectively using a four-point visual analogue scale . Both the refrigerant topical anesthetic spray and the placebo spray significantly reduced injection pain . Age was found to be an important factor influencing pain response in this study . Parental anxiety was not a significant factor influencing pain response . In addition , parents were not good at predicting their child 's pain . The results of the study support the use of an intervention , such as refrigerant topical anesthetic , as a practical , simple , and effective treatment strategy for reduction of short-term painful procedures like injections The contribution of training procedures design ed to alter individuals ' psychological responses to stressful life stimuli to the reduction of blood-pressure levels of hypertensives was evaluated . The treatment consisted of a set of coping skill-building experiences . Forty-one black males , mildly to moderately hypertensive and under medical supervision in an outpatient cardiovascular unit of a veterans ' hospital , participated . Subjects were r and omly assigned to one of three groups : Cognitive Self-Management Training ( CSM ) , Attention Placebo Control , and Current Clinic Conditions Control . The dependent measures were the State Anxiety Scale , Trait Anxiety Scale , Coping Strategic Inventory , systolic blood pressure , and diastolic blood pressure . Subjects in the CSM group reported significant increases in the use of cognitive coping strategies in their lives and demonstrated significant decreases in measured levels of state anxiety and systolic blood pressure . Promising reductions of diastolic blood pressure ratings were obtained as well BACKGROUND In a single-blind placebo-controlled study design we investigated the efficacy of acupuncture additionally applied to drug treatment in major depression . METHODS We r and omly included 70 in patients with a major depressive episode in three different treatment groups : verum acupuncture , placebo acupuncture and a control group . All three groups were pharmacologically treated with the antidepressant mianserin . The verum group received acupuncture at specific points considered effective in the treatment of depression . The placebo group was treated with acupuncture at non-specific locations and the control group received pharmacological treatment plus clinical management . Acupuncture was applied three times a week over a period of 4 weeks . Psychopathology was rated by judges blind to verum/placebo conditions twice a week over 8 weeks . RESULTS Patients who experienced acupuncture improved slightly more than patients treated with mianserin alone . CONCLUSIONS Additionally applied acupuncture improved the course of depression more than pharmacological treatment with mianserin alone . However , we could not detect any differences between placebo and verum acupuncture PURPOSE Postoperative pain control has received increasing attention by health care providers in the new millennium . In fact , pain was called the " sixth vital sign " by the Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) in 2001 . The continued challenge of effective , safe analgesia in the outpatient setting has promoted the use of various devices design ed to deliver local anesthetic directly to the surgical site . We endeavored to evaluate the efficacy of one such device currently in use . TYPE OF STUDY Prospect i ve , r and omized , placebo-controlled , double-blinded study . METHODS In this study , 49 consecutive patients were prospect ively enrolled and r and omly assigned to 1 of 3 groups after anterior cruciate ligament ( ACL ) reconstruction . Patients and investigators were blinded to group assignment . Group 1 ( control group ) received no catheter . Group 2 ( placebo group ) received an infusion catheter filled with saline . Group 3 ( experimental group ) received the same catheter filled with 0.25 % bupivacaine solution . All patients received an ipsilateral femoral nerve block with 30 mL 0.25 % bupivacaine and 20 mL 0.25 % bupivacaine intra-articular injection . Patients recorded narcotic consumption and pain levels on visual analogue scales twice a day for 4 days after surgery . The catheters were removed on day 4 and physical therapy performance was recorded . The patients were then asked to continue to record pain ratings and medication consumption for an additional 4 days after catheter removal . All patients underwent bone-patellar tendon-bone ACL reconstruction by the senior author ( P.D.F. ) . Seven patients were excluded from the study for ineffective femoral nerve block or catheter disconnection or occlusion . Narcotic consumption and the maximum , minimum , and median pain ratings were analyzed by analysis of variance . RESULTS Median pain ratings show lower pain levels ( P < .03 ) for both catheter groups versus the control group . No significant differences were found between the catheter groups for the median pain ratings , but lower maximum pain ratings were seen in the bupivacaine group compared with both placebo and no-catheter control subjects . Postoperative narcotic consumption was also lower in both catheter groups versus control subjects ( P < .03 ) . Physical therapy data revealed no difference in range of motion on postoperative day 4 . More patients were able to perform straight leg raises during the first therapy session in both the saline placebo catheter group ( 70 % ) and bupivacaine group ( 72 % ) compared with the control group ( 50 % ) . CONCLUSIONS The data suggest some element of placebo benefit at median pain ratings but a protective effect of the bupivacaine at maximum pain levels OBJECTIVE To test that methylpheni date combined with intensive multimodal psychosocial intervention , which includes social skills training , significantly enhances social functioning in children with attention-deficit/hyperactivity disorder ( ADHD ) compared with methylpheni date alone and methylpheni date plus nonspecific psychosocial treatment ( attention control ) . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to receive ( 1 ) methylpheni date alone , ( 2 ) methylpheni date plus multimodal psychosocial treatment that included social skills training , or ( 3 ) methylpheni date plus attention control treatment . Assessment s included parent , child , and teacher ratings of social function and direct school observations in gym . RESULTS No advantage was found on any measure of social functioning for the combination treatment over methylpheni date alone or methylpheni date plus attention control . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In young children with ADHD , there is no support for clinic-based social skills training as part of a long-term psychosocial intervention to improve social behavior . Significant benefits from methylpheni date were stable over 2 years 1,218 smokers able to quit smoking for 48 hr were r and omly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment . A pharmacologic factor contained four levels : nicotine polacrilex ( gum ) delivered ad lib or on a fixed regimen , placebo gum , and no gum . A self-guided behavioral treatment factor contained three levels : self-selected relapse prevention modules , r and omly administered modules , and no modules . Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups . The fixed regimen accounted for most of the effect for gum . There was no effect for the relapse prevention module factor . Men and women showed a differential treatment response . Men who received nicotine gum were more likely to be abstinent at each follow-up ( 2 , 6 , and 12 months ) . No treatment was significantly better among women . We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed A variety of factors may influence outcome measures in longitudinal studies , including placebo , Hawthorne , or natural history effects . Quality of life ( QoL ) measures are particularly subject to these phenomena . This 2-month postal survey was set up to examine the extent of nonspecific effects in a treatment ( vitamin supplementation ) group ( n = 180 ) , a placebo group ( n = 180 ) , as part of a stratified , r and omized controlled trial , and two control groups ( n = 768 each ) . Quality of life was measured using the SF36 . The placebo effect had a significant impact on improving physical , mental , and pain dimensions ( p = 0.02 to 0.04 ) , and the Hawthorne effect was significant ( p = 0.03 to 0.009 ) for psychological dimensions . Although the impact of natural history was not significant , it tended to worsen all QoL dimensions . Vitamin supplementation had no effect on QoL. These results demonstrate the importance of placebo and Hawthorne effects and suggest that they may be responsible for misleading results or reductions in the power of controlled trials In order to assess the effects of a Behavioral Treatment Program in the control of primary hypertension , twenty one unmedicated hypertensives were r and omly allocated to three groups : first , a treatment group ( BHG ) receiving a Behavioral Treatment which included : deep muscle relaxation , peripheral temperature Biofeedback and anxiety management training ; second , the placebo attention control group ( PHG ) and third , a control group of hypertensives too ( CHG ) . Additionally , were compared with seven normotensives subjects ( CNG ) . The post-treatment measures showed a significant reduction ( p < 0.001 ) in systolic and diastolic values only in the ( BHG ) . In a six months follow-up the ( BHG ) group still showed a significant reduction in the systolic and diastolic BP ( p < 0.02 ; p < 0.01 ) . Moreover individual variations in response to treatment were observed in this group , ( BHG ) BACKGROUND Acupuncture is widely used by patients with low back pain , although its effectiveness is unclear . We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with chronic low back pain . METHODS Patients were r and omized to treatment with acupuncture , minimal acupuncture ( superficial needling at nonacupuncture points ) , or a waiting list control . Acupuncture and minimal acupuncture were administered by specialized acupuncture physicians in 30 outpatient centers , and consisted of 12 sessions per patient over 8 weeks . Patients completed st and ardized question naires at baseline and at 8 , 26 , and 52 weeks after r and omization . The primary outcome variable was the change in low back pain intensity from baseline to the end of week 8 , as determined on a visual analog scale ( range , 0 - 100 mm ) . RESULTS A total of 298 patients ( 67.8 % female ; mean + /- SD age , 59 + /- 9 years ) were included . Between baseline and week 8 , pain intensity decreased by a mean + /- SD of 28.7 + /- 30.3 mm in the acupuncture group , 23.6 + /- 31.0 mm in the minimal acupuncture group , and 6.9 + /- 22.0 mm in the waiting list group . The difference for the acupuncture vs minimal acupuncture group was 5.1 mm ( 95 % confidence interval , -3.7 to 13.9 mm ; P = .26 ) , and the difference for the acupuncture vs waiting list group was 21.7 mm ( 95 % confidence interval , 13.9 - 30.0 mm ; P<.001 ) . Also , at 26 ( P=.96 ) and 52 ( P=.61 ) weeks , pain did not differ significantly between the acupuncture and the minimal acupuncture groups . CONCLUSION Acupuncture was more effective in improving pain than no acupuncture treatment in patients with chronic low back pain , whereas there were no significant differences between acupuncture and minimal acupuncture Abstract Recent research in the treatment of insomnia by paradoxical intention has utilized two different methods of instruction . Studies utilizing the r and om assignment of subjects to treatment groups employ a procedure in which clients are provided with a straight-forward explanation based on the present authors ' underst and ing of the use of paradoxical intention with insomnia ( type A administration ) . In contrast , controlled case studies have employed reframing , a procedure which explains the need for the paradoxical intention in a manner which best suits the specific underst and ing of the individual client ( type B administration ) . The present study employed the type B method in a design employing the r and om assignment of clients to groups . Three additional groups ( type A administration , placebo control , no-treatment control ) completed the design . The results indicated that the type A method was superior to the type B procedure when the same method for administering paradoxical intention was applied to a r and omized group of individuals Drug trials design ed to modify the progression of Alzheimer 's disease ( AD ) have required the development of mental state and behavior evaluation instruments that are sensitive to cognitive decline and measure skills useful in everyday living . We describe a videotaped home behavior ( VHB ) assessment instrument with high construct validity and reliability and a strong relationship to criterion references . The VHB was employed to test the hypothesis that aluminum is an important pathogenic factor in AD . The trivalent chelating agent desferrioxamine ( DFO ) , 125 mg i.m . twice daily five days per week , was used in a r and omized single-blind , oral lecithin , placebo-controlled clinical trial in 48 patients with AD . Analysis showed that the treatment and no-treatment groups were closely matched at entry into the trial but that the rate of decline , as measured by the VHB over 2 years of observation , was twice as rapid in the no-treatment group compared with the DFO-treated group . Furthermore , trace-metal analysis of autopsied brain confirmed that extended treatment with DFO lowered neocortical brain aluminum concentrations to near control concentrations . Aluminum ion-specific chelation may be a useful palliative treatment for AD , and further clinical trials are indicated STUDY DESIGN Prospect i ve , experimental , r and omized , single-factor , pretest/posttest design . OBJECTIVES To examine the effects of a calcaneal and Achilles-tendon-taping technique , utilizing only 4 pieces of tape and not involving the medial arch , on the symptoms of plantar heel pain . BACKGROUND Plantar fasciitis is one of the most common causes of heel and foot pain . Physical therapists have applied many techniques in an attempt to relieve the symptoms of plantar heel pain , including various taping methods for which there is little existing evidence . METHODS AND MEASURES Subjects ( n=41 ) were r and omly assigned into 4 groups : ( 1 ) stretching of the plantar fascia , ( 2 ) calcaneal taping , ( 3 ) control ( no treatment ) , and ( 4 ) sham taping . A visual analog scale ( VAS ) for pain and a patient-specific functional scale ( PSFS ) for functional activities were measured pretreatment and after 1 week of treatment ( posttreatment ) . RESULTS A significant difference was found posttreatment among the groups for the VAS ( P < .001 ) . Specifically , significant differences were found between stretching and calcaneal taping ( mean + SD , 4.6 + /- 0.7 versus 2.7 + /- 1.8 ; P = .006 ) , stretching and control ( mean + /- SD , 4.6 + /- 0.7 versus 6.2 + /- 1.0 ; P = .026 ) , calcaneal taping and control ( mean + /- SD , 2.7 + /- 1.8 versus 6.2 + /- 1.0 ; P < .001 ) , and calcaneal taping and sham taping ( mean + /- SD , 2.7 + /- 1.8 versus 6.0 + /- 0.9 ; P < .001 ) . No significant difference among groups was found for posttreatment PSFS ( P = .078 ) . CONCLUSIONS Calcaneal taping was shown to be a more effective tool for the relief of plantar heel pain than stretching , sham taping , or no treatment This study was design ed to assess the efficacy of oral transmucosal fentanyl citrate ( OTFC ) for premedication in an adult population and to determine its effects on anxiety , sedation , gastric volume , and gastric fluid acidity . The fentanyl citrate is incorporated in a lozenge mounted on a h and le ( oralet ) . The effects of OTFC , placebo oralet , and no premedication were compared in a prospect i ve , double-blind study on 90 adult ASA physical status I and II patients undergoing same-day admission surgery . Patients were r and omly assigned to one of three groups : OTFC group ( n = 30 ) , placebo group ( n = 30 ) , and control group ( n = 30 ) . Arterial blood pressure , heart rate , respiratory frequency , and oxygen saturation determined by pulse oximetry were recorded before any premedication was given , and then every 10 min until the patient was taken to the operating room . Baseline anxiety and sedation levels were assessed to ensure group similarity immediately before premedication was given and at the more anxiety-provoking phase upon entering the operating room . Anxiety levels were rated using the Spielberger State-Trait Anxiety Inventory short form and sedation levels were assessed with the Ramsay scale . Side effects , as reported by the patients , were also recorded . Gastric contents were aspirated via an orogastric tube after induction of anesthesia and were measured for volume and pH. No significant differences were found among the three groups in mean arterial pressure , heart rate , or respiratory frequency . Initial oxygen saturation levels in all groups decreased after 30 min but not less than 96 % except for one patient in the OTFC group , who decreased to 88 % . On entering the operating room , the OTFC group demonstrated significantly higher levels of anxiolysis than the control group , but no significant differences were seen between the OTFC and the placebo groups or the placebo and control groups . Mean gastric volumes ( OTFC , 29 mL ; placebo , 26 mL ; control , 24 mL ) and pH ( OTFC , 2.0 ; placebo , 1.8 ; control , 2.1 ) were similar in all groups . There were no significant differences among the groups in levels of sedation achieved . Mild dizziness or light-headedness was the most commonly reported side effect in 23 % of the OTFC group . In the OTFC group , 71.4 % liked the premedicant effect as compared to 46.4 % of the placebo group . Most of the groups found the oralet method of premedicant delivery very acceptable . This study demonstrates that the OTFC oralet is an effective anxiolytic in adults . It has minimal side effects and is prepared in an acceptable format . There was no measurable increase in gastric contents or acidity in the oralet groups , compared to those patients who were given nothing by mouth . ( Anesth Analg 1996;82:158 - 61 Venipuncture continues to be considered a painful and unpleasant experience for those receiving medical treatment . A prospect i ve study investigating whether the application of a transcutaneous electrical nerve stimulator ( TENS ) decreases the complaints of pain and unpleasantness with i.v . needle insertion was conducted using a group of 71 subjects who were double-blinded and r and omized to one of three groups : TENS , placebo-TENS , and control . This article gives an overview of this research and describes its findings This study tested placebo responses in psychomotor performance when caffeine or alcohol was expected . Fifty male university students were assigned to one of four placebo groups or to a no-treatment control group . Two groups received placebo caffeine and two received placebo alcohol . Subjects performed 12 trials on a pursuit rotor task and performance was measured by the percent time on target . Then they received information about the expected drug effect on the task . One caffeine placebo group ( C+ ) and one alcohol placebo group ( A+ ) were led to expect enhanced performance on the task . The other caffeine placebo group ( C− ) and alcohol placebo group ( A− ) were led to expect impaired performance . Subjects subsequently performed 12 trials on the task . An interaction was obtained between the expected type of effect and the expected type of drug . The C+ group displayed superior performance compared to the C− group , and the reverse relationship was observed between the A+ and A− group . In addition , subjects led to expect alcohol-induced impairment ( A− ) performed better than subjects led to expect caffeine-induced impairment ( C− ) . Subjects also reported greater motivation to resist impairment when they expected alcohol rather than caffeine . The research indicates that underst and ing and predicting placebo responses may require consideration of the drug that is expected as well as its expected effect A placebo effect on post-operative swelling was investigated as a possible model for study ing psychological influences on recovery from surgery . 79 patients undergoing removal of impacted third-molars received one of five different procedures shortly after emerging from general anaesthetic . These included dentist-administered or placebo ultrasound ( the latter given in two different ways to control for massage effects ) , untreated controls and a group instructed to apply facial massage to themselves . Pre- and post-operative measurements included trait and state-anxiety , coping style , emotional state , pain , plasma cortisol and facial swelling . Cortisol levels correlated with anxiety and avoidant coping . Post-operative anxiety was negatively correlated with pre-operative arousal . Neither coping nor emotional state was affected by the treatments , but swelling was reduced by a placebo effect of ultrasound . Cortisol levels also responded , apparently to an effect of massage . The coping and emotional factors which we measured here can not , therefore , explain the effects of this psychological procedure on post-operative recovery Abstract Objectives : To investigate whether intensive cognitive behaviour therapy results in significant improvement in positive psychotic symptoms in patients with chronic schizophrenia . Design : Patients with chronic schizophrenia were r and omly allocated , stratified according to severity of symptoms and sex , to intensive cognitive behaviour therapy and routine care , supportive counselling and routine care , and routine care alone . Setting : Adjunct treatments were carried out in outpatient clinics or in the patient 's home . Subjects : 87 patients with persistent positive symptoms who complied with medication ; 72 completed treatment . Outcome measures : Assessment s of positive psychotic symptoms before treatment and 3 months after treatment . Number of patients who showed a 50 % or more improvement in symptoms . Exacerbation of symptoms and rates of readmission to hospital . Results : Significant improvements were found in the severity ( F=5.42 , df = 2,86 ; P=0.006 ) and number ( F=4.99 , df=2,86 ; P=0.009 ) of positive symptoms in those treated with cognitive behaviour therapy . The supportive counselling group showed a non-significant improvement . Significantly more patients treated with cognitive behaviour therapy showed an improvement of 50 % or more in their symptoms ( χ2=5.18 , df=1 ; P=0.02 ) . Logistic regression indicated that receipt of cognitive behaviour therapy results in almost eight times greater odds ( odds ratio 7.88 ) of showing this improvement . The group receiving routine care alone also experienced more exacerbations and days spent in hospital . Conclusions : Cognitive behaviour therapy is a potentially useful adjunct treatment in the management of patients with chronic schizophrenia A st and ard reminiscence interview and one that focused on successfully met challenges reduced state anxiety and enhanced coping self-efficacy when measured against both attention-placebo and no-intervention control groups in a sample of 104 elderly male patients facing surgery . Age-peer interviewers did not elicit significantly greater overall reductions in state anxiety or increases in coping self-efficacy scores than younger interviewers ( nonpeers ) , but did produce significantly higher coping self-efficacy scores than nonpeers when administering the challenge reminiscence interview & NA ; Individual differences in pharmacokinetics and pharmacodynamics , the type of pain and the method of drug administration can account for the response variability to analgesics . By integrating a clinical and an experimental approach , we report here that another important source of variability is represented by individual differences in non‐specific ( placebo ) activation of endogenous opioid systems . In the first part of this study , we analyzed the effectiveness of buprenorphine , tramadol , ketorolac and metamizol in the clinical setting , where the placebo effect was completely eliminated by means of hidden infusions . We found that the hidden injections were significantly less effective and less variable compared with open injections ( in full view of the subject ) , suggesting that part of the response variability was due to non‐specific factors ( placebo ) . Since we could not administer the opioid antagonist , naloxone , to these patients , in the second part of this study , we induced experimental ischemic arm pain in healthy volunteers and found that , as occurred in clinical pain , the analgesic response to a hidden injection of the non‐opioid ketorolac was less effective and less variable than an open injection . Most importantly , we obtained the same effects by adding naloxone to an open injection of ketorolac , thus blocking the opioid‐mediated placebo component of analgesia . These findings indicate that both the psychological ( hidden injection ) and pharmacological ( naloxone ) blockade of the placebo response reduce the effectiveness of , and the response variability to , analgesic drugs . Therefore , an important source of response variability to analgesics appears to be due to differences in non‐specific activation of endogenous opioid systems The comparative efficacy of prednisolone followed by interferon alfa ( IFN-alpha ) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen ( anti-HBe ) seroconversion has not been evaluated in a large cohort of white children . To determine this , a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children ( median age , 9 years [ range , 2 - 16 years ] ; 56 boys ; 84 [ 89 percent ] white ) , all having inflammatory changes on liver biopsy . Patients were r and omized to receive either prednisolone followed by IFN-alpha ( n = 34 ) ; placebo followed by IFN-alpha ( n = 30 ) ; or no treatment ( n = 31 ) . The prednisolone/placebo was given on a double-blind basis . Lymphoblastoid IFN-alpha was given at 5 MU/m(2 ) three times a week for 12 weeks . Baseline clinical , biochemical , and histological features were similar for the three groups . The majority ( 85 percent ) had a baseline aspartate aminotransferase ( AST ) level < or = 100 IU/L. On follow-up between 12 and 18 months ( median , 15 months ) after treatment , the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids ( 12 of 34 [ 35 percent ] ) or placebo [ 12 of 30 ( 40 percent ) ] as against controls ( 4 of 31 [ 13 percent ] , P < .05 ) . Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy . Our results show that in white children treatment with IFN-alpha , at the dose and duration used in this study , improves the rate of anti-HBe seroconversion . Steroid priming does not potentiate the effect of IFN-alpha To determine the effectiveness of nicotine polacrilex combined with self-administered relapse prevention material s in maintaining smoking cessation , we conducted a r and omized , double-blind , placebo controlled trial . Volunteers aged 18 to 65 years responding to media announcements were required to quit smoking for 48 hours without assistance . Of 1844 potential participants , 136 were medically excluded , 535 declined to make a quit attempt , and 573 were unable to quit , leaving 600 participants ( 35 % ) who were r and omized . Eight self-help relapse prevention modules were mailed weekly . Gum was used either ad lib for smoking urges or on a fixed , hourly schedule ( 12 pieces per day ) . Only 15 % of the subjects in each gum group stopped using the gum altogether because of side effects , but only 20 % of the ad lib groups and 40 % of the fixed-dosage group used at least eight pieces of gum per day during the first week . The abstinence rates ( for at least seven days ) at the six-month follow-up were 31 % in both active gum groups and 22 % in the placebo and no gum groups . Relapse rates in the two active gum groups were about half those in the placebo and no gum groups . Nicotine polacrilex may be a useful adjunct to minimal contact smoking cessation formats , which have broad appeal . Also , minimal contact relapse prevention programs may assist physicians in helping patients to maintain smoking cessation using nicotine polacrilex The National Institute of Mental Health ( NIMH ) Treatment of Depression Collaborative Research Program ( TDCRP ) is the first multisite coordinated study initiated by the NIMH in the field of psychotherapy research . Three research sites , using an identical research protocol , are investigating the effectiveness of two forms of brief psychotherapy ( cognitive behavior therapy and interpersonal psychotherapy ) in the treatment of outpatient depression . Three training sites have trained experienced therapists in a st and ard fashion for each of the psychotherapies and the comparison pharmacotherapy conditions . This report presents the background of the TDCRP , the rationale for the choice of patient population and treatment conditions , and the research plan for both the training/pilot phase and the outcome study currently in progress , and discusses the potential contributions of the program to the field of psychotherapy research Fifty-six adult males who were hospitalized with anxiety related problems were r and omly assigned to the conditions formed by a 2 ( instructions to increase heart rate , instructions to decrease heart rate ) × 3 ( true biofeedback , placebo biofeedback , no biofeedback ) factorial plus 1 ( no-treatment control ) design . Subjects were seen for 4 heart rate training/recording sessions and 1 subsequent transfer-test session . Results indicated that : a ) neither instructions alone nor the combinations of instructions and true or placebo biofeedback were more effective than simply sitting quietly ( adaptation ) for decreasing heart rate , b ) instructions plus true biofeedback was more effective than instructions alone or instructions plus placebo biofeedback for increasing heart rate , c ) multiple sessions of training did not enhance the level of control achieved early in the first session , d ) the control achieved with biofeedback did not transfer to a subsequent no-biofeedback situation , and e ) biofeedback training did not influence subjects ' subjective anxiety levels Abstract The present study evaluated the efficacy of cognitive-behavioural skills training , patterned after stress-inoculation training , as a preventive intervention for the attenuation of acute clinical pain during a noxious X-ray procedure — the knee arthrogram . Thirty-six adult male out patients were r and omly assigned to one of three groups : Skills Training . Attention-Placebo , and No-Treatment Control . An experimental pain test was administered before and after the interventions , as a generalization measure . Arthrogram pain was assessed by three dependent measures : patient 's ratings , radiologist 's ratings and videotape ratings completed by two‘blind ’ raters . The results failed to support the efficacy of skills training for the attenuation of acute clinical pain , or its generalization to the experimental pain test . Although Skills Training subjects reported using significantly more coping strategies during the arthrogram . many subjects in the two control groups also reported using their own spontaneous strategies . Equivocal data were obtained on the role of ‘ self-efficacy ’ expectancies in mediating pain behaviour and experience . Experimental pain threshold but not pain tolerance was significantly related to acute clinical pain experienced during the arthrogram CONTEXT High-dose chemotherapy poses considerable challenges to emesis management . Although prior studies suggest that acupuncture may reduce nausea and emesis , it is unclear whether such benefit comes from the nonspecific effects of attention and clinician-patient interaction . OBJECTIVE To compare the effectiveness of electroacupuncture vs minimal needling and mock electrical stimulation or antiemetic medications alone in controlling emesis among patients undergoing a highly emetogenic chemotherapy regimen . DESIGN Three-arm , parallel-group , r and omized controlled trial conducted from March 1996 to December 1997 , with a 5-day study period and a 9-day follow-up . SETTING Oncology center at a university medical center . PATIENTS One hundred four women ( mean age , 46 years ) with high-risk breast cancer . INTERVENTIONS Patients were r and omly assigned to receive low-frequency electroacupuncture at classic antiemetic acupuncture points once daily for 5 days ( n = 37 ) ; minimal needling at control points with mock electrostimulation on the same schedule ( n = 33 ) ; or no adjunct needling ( n = 34 ) . All patients received concurrent triple antiemetic pharmacotherapy and high-dose chemotherapy ( cyclophosphamide , cisplatin , and carmustine ) . MAIN OUTCOME MEASURES Total number of emesis episodes occurring during the 5-day study period and the proportion of emesis-free days , compared among the 3 groups . RESULTS The number of emesis episodes occurring during the 5 days was lower for patients receiving electroacupuncture compared with those receiving minimal needling or pharmacotherapy alone ( median number of episodes , 5 , 10 , and 15 , respectively ; P<.001 ) . The electroacupuncture group had fewer episodes of emesis than the minimal needling group ( P<.001 ) , whereas the minimal needling group had fewer episodes of emesis than the antiemetic pharmacotherapy alone group ( P = .01 ) . The differences among groups were not significant during the 9-day follow-up period ( P = .18 ) . CONCLUSIONS In this study of patients with breast cancer receiving high-dose chemotherapy , adjunct electroacupuncture was more effective in controlling emesis than minimal needling or antiemetic pharmacotherapy alone , although the observed effect had limited duration . JAMA . 2000;284:2755 - 2761 & NA ; There is some evidence for the efficacy of acupuncture in chronic low‐back pain ( LBP ) , but it remains unclear whether acupuncture is superior to placebo . In a r and omized , blinded , placebo‐controlled trial , we evaluated the effect of traditional acupuncture in chronic LBP . A total of 131 consecutive out‐ patients of the Department of Orthopaedics , University Goettingen , Germany , ( age=48.1 years , 58.5 % female , duration of pain : 9.6 years ) with non‐radiating LBP for at least 6 months and a normal neurological examination were r and omized to one of three groups over 12 weeks . Each group received active physiotherapy over 12 weeks . The control group ( n=46 ) received no further treatment , the acupuncture group ( n=40 ) received 20 sessions of traditional acupuncture and the sham‐acupuncture group ( n=45 ) 20 sessions of minimal acupuncture . Changes from baseline to the end of treatment and to 9‐month follow‐up were assessed in pain intensity and in pain disability , and secondary in psychological distress and in spine flexion , compared by intervention groups . Acupuncture was superior to the control condition ( physiotherapy ) regarding pain intensity ( P=0.000 ) , pain disability ( P=0.000 ) , and psychological distress ( P=0.020 ) at the end of treatment . Compared to sham‐acupuncture , acupuncture reduced psychological distress ( P=0.040 ) only . At 9‐month follow‐up , the superiority of acupuncture compared to the control condition became less and acupuncture was not different to sham‐acupuncture . We found a significant improvement by traditional acupuncture in chronic LBP compared to routine care ( physiotherapy ) but not compared to sham‐acupuncture . The trial demonstrated a placebo effect of traditional acupuncture in chronic LBP Fifty-six alcoholics ( 49 male , 7 female ) of lower socioeconomic class attending an outpatient treatment program in Brooklyn , New York were prospect ively r and omized to one of three treatment group : point-specific acupuncture , sham transdermal stimulation or st and ard care ( control ) . One third of the subjects reported a history of drug use in addition to alcohol . Results in this small sample showed no significant differences in attendance at Alcoholics Anonymous meetings , number of out patients sessions attended , number of weeks in either the study or in the outpatient program , number of persons completing treatment or in the number of relapses . It is therefore concluded that in this small racially mixed sample of urban outpatient alcoholics , fixed point-specific st and ardized acupuncture did not improve outcome . We caution against the routine use of this treatment until more r and omized controlled trials demonstrate a beneficial effect Fifty out patients with mild , chronic , mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were r and omly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks . Half of the patients in each condition relapsed within 6 weeks , indicating that pill-taking itself does not influence maintenance of placebo response . Placebo response was more likely to be maintained in patients who were currently married . At the end of 3 months , the overall relapse rate was 58 % . The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials , and they discuss limits on the generalizability of their findings Thirty-three patients in long-term individual therapy were referred to one of three weekend groups : two experimental ( affect-arousing , gestalt therapy ) groups and one control ( meditation-Tai Chi ) group . The impact of the weekend group experience ( WGE ) on individual therapy was examined six and 12 weeks later . At six weeks the patients in the experimental groups showed , on some measures , a significantly greater improvement in their individual therapy than did controls . By 12 weeks , there were no demonstrable differences . The WGE was not without risk : even though the group leaders were highly trained , responsible clinicians , two patients suffered considerable psychological damage . The control ( meditation-Tai Chi ) group offered a relatively innocuous experience ; there was no risk , but few members found the specific procedures useful in their lives . Intense affect arousal in the WGE was not related to positive change in subsequent individual therapy . Those expressing the greatest affect in either experimental group were no more likely to have had a measurable positive impact on their subsequent individual therapy than patients expressing little or no measurable affect Abstract Objective To investigate whether a sham device ( a vali date d sham acupuncture needle ) has a greater placebo effect than an inert pill in patients with persistent arm pain . Design A single blind r and omised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls . Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study . Setting Academic medical centre . Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale . Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks . Main outcome measures Arm pain measured on a 10 point pain scale . Secondary outcomes were symptoms measured by the Levine symptom severity scale , function measured by Pransky 's upper extremity function scale , and grip strength . Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups , but changes were not different between the groups ( −0.14 , 95 % confidence interval −0.52 to 0.25 , P = 0.49 ) . Changes in severity scores for arm symptoms and grip strength were similar between groups , but arm function improved more in the placebo pill group ( 2.0 , 0.06 to 3.92 , P = 0.04 ) . Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group ( −0.33 ( −0.40 to −0.26 ) v −0.15 ( −0.21 to −0.09 ) , P = 0.0001 ) and on the symptom severity scale ( −0.07 ( −0.09 to −0.05 ) v −0.05 ( −0.06 to −0.03 ) , P = 0.02 ) . Differences were not significant , however , on the function scale or for grip strength . Reported adverse effects were different in the two groups . Conclusions The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in . Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals PURPOSE To examine the effects of aerobic exercise therapy on quality of life ( QoL ) and associated outcomes in women treated for breast cancer . Evidence suggests that exercise may be beneficial , but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients . PATIENTS AND METHODS A total of 108 women who had been treated for breast cancer 12 to 36 months previously were r and omly assigned to supervised aerobic exercise therapy ( n = 34 ) , exercise-placebo ( body conditioning ; n = 36 ) , or usual care ( n = 38 ) . Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks . Outcomes included QoL , depression , exercise behavior , aerobic fitness ; outcomes were assessed at baseline and at the 8- and 24-week follow-up . RESULTS Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General ( primary outcome ) favoring aerobic exercise therapy at 8 weeks , relative to usual care . Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast , social/family well-being , functional well-being , and breast cancer subscale scores at 8-week follow-up . Psychological health outcomes improved modestly for both intervention groups ; these improvements were sustained for several end points . CONCLUSION Exercise therapy had large , clinical ly meaningful , short-term beneficial effects on QoL in women treated for breast cancer ; this finding can not be attributable to attention , given that the exercise-placebo group did not report similar effects relative to usual care Protocol was carried out on 98 patients who were divided into three groups selected as ( one control group , two " placebo " group , and three treated with acupuncture ) . This protocol showed that it was possible to improve cervical maturation if acupuncture sessions were carried out at the beginning of the 9th month . The Bishop scores in the three groups after 10 days interval show that there was a significant progression of 2.61 points in the group treated with acupuncture as against only 0.89 and 1.08 in the placebo and control groups Background and Objectives Conventional treatments are often ineffective for patients having painful abdominal scars . There are painful points in and around scar tissue . We tested the hypothesis that insertion of intradermal needles into these painful points reduces scar pain . Methods Patients with abdominal scar pain with painful points that is not relieved by conventional treatments were allocated to a treatment group ( n = 23 ) , a sham-treatment group ( n = 23 ) , or a control group ( n = 24 ) . In the treatment group , intradermal needles were inserted into painful points detected by a pressure threshold meter ( pain ≤ 2.5 kg/cm2 ) . In the sham-treatment group , the same needles were inserted into nonpainful points . The needles were kept in place for 24 hours . This process was repeated 20 times over a 4-week period . Responses were evaluated before and at the end of treatment , and 4 and 26 weeks after the treatment . Continuous and lancinating pain was evaluated on a 10-cm visual analog scale . We measured the area of pain and the pressure required to initiate painful-point pain . All patients took diclofenac as needed and completed a diary of daily diclofenac consumption . Results Patients in the treatment group showed a marked reduction in all pain parameters ( > 70 % ) . In contrast , analgesia was minimal in the other groups . The decreases in the pain threshold pressure correlated with the decreases in continuous and lancinating pain ( r = .57 and r = .63 , respectively ) . Conclusion Our data suggest that insertion of intradermal needles into painful points is a remarkably effective treatment for intractable abdominal scar pain . Analgesia presumably results from inactivation of painful points , through a yet to be eluci date d mechanism Abstract Objective To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache . Design Three armed r and omised controlled multicentre trial . Setting 28 outpatient centres in Germany . Participants 270 patients ( 74 % women , mean age 43 ( SD 13 ) years ) with episodic or chronic tension-type headache . Interventions Acupuncture , minimal acupuncture ( superficial needling at non-acupuncture points ) , or waiting list control . Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks . Main outcome measure Difference in numbers of days with headache between the four weeks before r and omisation and weeks 9 - 12 after r and omisation , as recorded by participants in headache diaries . Results The number of days with headache decreased by 7.2 ( SD 6.5 ) days in the acupuncture group compared with 6.6 ( SD 6.0 ) days in the minimal acupuncture group and 1.5 ( SD 3.7 ) days in the waiting list group ( difference : acupuncture v minimal acupuncture , 0.6 days , 95 % confidence interval -1.5 to 2.6 days , P = 0.58 ; acupuncture v waiting list , 5.7 days , 3.9 to 7.5 days , P < 0.001 ) . The proportion of responders ( at least 50 % reduction in days with headache ) was 46 % in the acupuncture group , 35 % in the minimal acupuncture group , and 4 % in the waiting list group . Conclusions The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache . Trial registration number IS RCT N9737659 Abstract Objectives : To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers . To determine the synergistic analgesic effect of sucrose and pacifiers . Design : R and omised prospect i ve study with vali date d behavioural acute pain rating scale . Setting : Maternity ward . Participants : 150 term newborns undergoing venepuncture r and omly assigned to one of six treatment groups : no treatment ; placebo ( 2 ml sterile water ) ; 2 ml 30 % glucose ; 2 ml 30 % sucrose ; a pacifier ; and 2 ml 30 % sucrose followed by a pacifier . Results : Median ( interquartile ) pain scores during venepuncture were 7 ( 5 - 10 ) for no treatment ; 7 ( 6 - 10 ) for placebo ( sterile water ) ; 5 ( 3 - 7 ) for 30 % glucose ; 5 ( 2 - 8 ) for 30 % sucrose ; 2 ( 1 - 4 ) for pacifier ; and 1 ( 1 - 2 ) for 30 % sucrose plus pacifier . Mann-Whitney U test P values for comparisons of 30 % glucose , 30 % sucrose , pacifier , and 30 % sucrose plus pacifier versus placebo ( sterile water ) were 0.005 , 0.01 , < 0.0001 , and < 0.0001 , respectively . Differences between group median pain scores for these comparisons were 2 ( 95 % confidence interval 1 to 4 ) , 2 ( 0 to 4 ) , 5 ( 4 to 7 ) , and 6 ( 5 to 8) , respectively . P values for comparisons of 30 % glucose , 30 % sucrose , and 30 % sucrose plus pacifier versus pacifier were 0.0001 , 0.001 , and 0.06 , respectively . Differences between group medians for these comparisons were 3 ( 2 to 5 ) , 3 ( 1 to 5 ) , and 1 ( 0 to 2 ) , respectively . Conclusion : The analgesic effects of concentrated sucrose and glucose and pacifiers are clinical ly apparent in newborns , pacifiers being more effective than sweet solutions . The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone . These simple and safe interventions should be widely used for minor procedures in neonates . Key messages The analgesic effects on newborn infants of sucrose , glucose , and pacifiers can be clearly detected by a behavioural pain rating scale Pacifiers had a better analgesic effect than sweet solutions A synergistic effect was found with a combination of sucrose and pacifiers Sweet solutions and pacifiers constitute simple and safe interventions that can be used to provide analgesia in newborns during minor The logic of the r and omized double-blind placebo control group design is presented , and problems with using the design in psychotherapy are discussed . Placebo effects are estimated by examining clinical trials in medicine and psychotherapy . In medicine , a recent meta- analysis of clinical trials with treatment , placebo , and no treatment arms was conducted ( Hróbjartsson & Gøtzsche , 2001 ) , and it was concluded that placebos have small or no effects . A re- analysis of those studies , presented here , shows that when disorders are amenable to placebos and the design is adequate to detect the effects , the placebo effect is robust and approaches the treatment effect . For psychological disorders , particularly depression , it has been shown that pill placebos are nearly as effective as active medications whereas psychotherapies are more effective than psychological placebos . However , it is shown that when properly design ed , psychological placebos are as effective as accepted psychotherapies Objective : To find evidence of classically conditioned placebo effects in a placebo‐controlled crossover drug study . Specifically , we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before It seems sensible to tailor treatments of insomnia in relation to the presenting characteristics of the sleeper and of the complaint . This report describes the first study formally to examine the comparative effectiveness of tailored and untailored ( r and omly allocated ) treatments . We developed a question naire to facilitate the design ing of individualized programmes . Results indicated that statistical analysis may underestimate the benefits of tailoring . Measures of clinical ly significant change , however , suggested that tailored treatment though it may be highly effective , is no more so than stimulus control therapy We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain . Different types of placebo analgesic responses were evoked by means of cognitive expectation cues , drug conditioning , or a combination of both . Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine . Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone . Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone . Morphine conditioning alone ( without expectation cues ) induced a naloxone-reversible placebo effect . By contrast , ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially . Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive . Therefore , we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or , otherwise , naloxone-insensitive , depending on the procedure used to evoke the placebo response . These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia , and this balance is crucial for the activation of opioid or nonopioid systems . Expectation triggers endogenous opioids , whereas conditioning activates specific subsystems . In fact , if conditioning is performed with opioids , placebo analgesia is mediated via opioid receptors , if conditioning is performed with nonopioid drugs , other nonopioid mechanisms result to be involved Background and Purpose — There is inconclusive evidence of the effectiveness of psychological interventions for depression after stroke . We report the results from a r and omized controlled trial of cognitive behavioral therapy ( CBT ) . Methods — Stroke patients admitted to hospital were invited to complete mood question naires 1 , 3 and 6 months after stroke . Patients who were depressed were invited to take part in a trial and r and omly allocated to receive CBT ( n=39 ) , an attention placebo intervention ( n= 43 ) , or st and ard care ( n=41 ) . Outcome assessment s were undertaken at 3 and 6 months after recruitment , on the Beck Depression Inventory , Wakefield Depression Inventory , Extended Activities of Daily Living scale , London H and icap Scale , and a rating of satisfaction with care . Results — There were no significant differences between the groups in patients ’ mood , independence in instrumental activities of daily living , h and icap , or satisfaction with care . Conclusions — CBT in the treatment of depression following stroke was found to be ineffective in this study . However , because of the small sample size , method of recruitment , and selection criteria , further r and omized trials are required Abstract Objectives : To determine whether a home based exercise programme can improve outcomes in patients with knee pain . Design : Pragmatic , factorial r and omised controlled trial of two years ' duration . Setting : Two general practice s in Nottingham . Participants : 786 men and women aged—45 years with self reported knee pain . Interventions : Participants were r and omised to four groups to receive exercise therapy , monthly telephone contact , exercise therapy plus telephone contact , or no intervention . Patients in the no intervention and combined exercise and telephone groups were r and omised to receive or not receive a placebo health food tablet . Main outcome measures : Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities ( WOMAC ) osteoarthritis index at two years . Secondary outcomes included knee specific physical function and stiffness ( scored on WOMAC index ) , general physical function ( scored on SF-36 question naire ) , psychological outlook ( scored on hospital anxiety and depression scale ) , and isometric muscle strength . Results : 600 ( 76.3 % ) participants completed the study . At 24 months , highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups ( mean difference -0.82 , 95 % confidence interval -1.3 to -0.3 ) . Similar improvements were observed at 6 , 12 , and 18 months . Regular telephone contact alone did not reduce pain . The reduction in pain was greater the closer patients adhered to the exercise plan . Conclusions : A simple home based exercise programme can significantly reduce knee pain . The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist BACKGROUND Nausea and vomiting in early pregnancy are troublesome symptoms for some women . We undertook a single blind r and omized controlled trial to determine whether acupuncture reduced nausea , dry retching , and vomiting , and improved the health status of women in pregnancy . METHODS The trial was undertaken at a maternity teaching hospital in Adelaide , Australia , where 593 women less than 14 weeks ' pregnant with symptoms of nausea or vomiting were r and omized into 4 groups : traditional acupuncture , pericardium 6 ( p6 ) acupuncture , sham acupuncture , or no acupuncture ( control ) . Treatment was administered weekly for 4 weeks . The primary outcomes were nausea , dry retching , vomiting , and health status . Comparisons were made between groups over 4 consecutive weeks . RESULTS Women receiving traditional acupuncture reported less nausea ( p < 0.01 ) throughout the trial and less dry retching ( p < 0.01 ) from the second week compared with women in the no acupuncture control group . Women who received p6 acupuncture ( p < 0.05 ) reported less nausea from the second week of the trial , and less dry retching ( p < 0.001 ) from the third week compared with women in the no acupuncture control group . Women in the sham acupuncture group ( p < 0.01 ) reported less nausea and dry retching ( p < 0.001 ) from the third week compared with women in the no acupuncture group . No differences in vomiting were found among the groups at any time . CONCLUSION Acupuncture is an effective treatment for women who experience nausea and dry retching in early pregnancy . A time-related placebo effect was found for some women In Experiment 1 , 28 attention-deficit hyperactivity disorder ( ADHD ) boys underwent a double-blind , placebo-controlled medication assessment in a summer day-treatment program . Daily , boys were asked questions to assess their attributions for and evaluations of their behavior . Objective measures showed improved behavior with methylpheni date ; however , boys tended to attribute their performance to effort rather than to medication , particularly when medicated . Experiment 2 involved 38 ADHD boys the following summer and replicated the procedures in Experiment 1 , with the addition of a no-pill condition and a comparison of attributions for success and failure outcomes . Simply taking a pill ( no-pill vs. placebo comparison ) did not show significant effects , whereas the results of Experiment 1 were replicated with placebo-methylpheni date comparisons . Across drug conditions a self-enhancing attributional pattern was obtained ; the majority of attributions for success were to ability or effort , whereas attributions for failure were to the pill or to counselors This study compared two behavioral treatments for marital discord with a nonspecific control and a waiting-list control . The behavioral treatments combined training in problem-solvi ng skills with training in contingency management procedures , differing only with respect to the contracting form : One group learned to form good faith contracts , and the other , quid pro quo contracts . Thirty-two couples were r and omly assigned to one of these treatment conditions and one of three therapists . Improvement was assessed by two observational measures and by two self-report question naires . On all measures , both behavioral groups improved significantly more than waiting-list couples . On three of the four measures , behavioral couples improved significantly more than nonspecific couples . The two behavioral groups did not differ from one another on any of the measures . Although an increasing number of reports have attested to the effectiveness of using social-learning principles in treating marital problems , most of these reports consist of uncontrolled case studies ( cf . Jacobson The effects of three group treatment formats on 20 men with secondary erectile dysfunction and their partners were contrasted . After a comprehensive medical and psychological screening , each couple was assigned to one of three treatment groups ( Communication Technique Training , Sexual Technique Training , Combination Treatment ) or to one of two control groups ( Attention-Placebo , No-Treatment ) . Couples in the three treatment groups and the attention-placebo group participated in their respective formats in twice-weekly sessions for a total of 20 hours . The no-treatment control group received sex education and treatment after a 5-week waiting list period . All three treatment groups fostered substantial gains so that between-format differences were not statistically significant . Subject variables which predicted success/experience ratio gains included age of the male partner , perceived level of relationship adjustment , and the male partner 's success/experience ratio prior to treatment . Eighty-one percent of the treated men reached the criterion of 80 % or greater success/experience ratio ( successful penetration and subsequent ejaculation ) at the 6-month follow-up . Good nocturnal tumescence prior to treatment was correlated with a better treatment outcome than poor tumescence & NA ; The aim of this study was to investigate the effectiveness of pulsed short wave ( PSW ) in the relief of pain in osteoarthritis of the hip and knee . Ninety‐two patients , mean age 63 years , ( 34 men and 58 women ) were r and omly allocated to one of three groups : ( 1 ) Active PSW , using the dosage found in a pilot study to be non‐significantly most effective , ( 2 ) Placebo PSW , ( 3 ) No treatment control group . Nine sessions of treatment were provided over a 3‐week period , each application lasting for 15 min . The machine was modified by the manufacturers so that the therapist was able to administer the treatment and carry out assessment s without being aware of the treatment allocation . Outcome measures included sensory and affective pain diary reports averaged over days and weeks , self‐reported benefit and the General Health Question naire . Analysis of variance with repeated measures over time was used to find out if the active treatment had a specific effect , incremental to the placebo effect . There were no significant differences between the active and placebo groups over time . According to the pain diary reports , both active and placebo groups tended to improve slightly during treatment , but worsened after its withdrawal . Patients who were given the placebo application tended to report more benefit than those who had the active treatment , although this did not quite reach statistical significance ( P < 0.06 ) . Patients who were not on a waiting list for surgery did significantly better over time than those who were ( P < 0.03 ) . There were no significant differences between the groups over time for the other outcome variables . Any treatment effect on this patient population appears to have been largely placebo‐mediated . No evidence was found therefore for the specific effectiveness of PSW for treatment of osteoarthritic hip or knee pain Depressives responding to initial treatment were maintained on amitriptyline for eight months , withdrawn double-blind to placebo after two months , or withdrawn overtly onto no medication . In each group half the patients received weekly psychotherapy and half were seen once monthly . Effects on symptom ratings were examined . Maintenance amitriptyline gave a significant advantage over early withdrawal in preventing symptom recrudescence . There were no differences between double-blind or overt withdrawal . There were no interactions between drug withdrawal and psychotherapy . Psychotherapy produced no significant advantages over low contact on symptoms , although it did improve social adjustment ratings reported elsewhere Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems . Recently , we showed that placebos may also produce respiratory depressant responses , a typical side-effect of narcotics , when a subject had a prior experience of respiratory depression in the course of narcotic treatment . In the present study , we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine . The placebo respiratory depressant effect that result ed from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone , indicating that it was mediated by endogenous opioids . These findings show that placebos act , via the activation of opioid receptors , not only on pain mechanisms but on the respiratory centres as well , thus mimicking a typical side-effect of narcotics . In addition , the experimental procedure we used did not produce any expectation of respiratory depression and , similarly , the subjects did not notice any sign of respiratory discomfort . Thus , the placebo respiratory depression elicited in the present study can not be explained on the basis of cognitive or motivational mechanisms . Rather , it appears to be a sequence effect due to learning , thus suggesting a conditioning mechanism mediated by endogenous opioids Those who were labelled as depressives in a rural survey were r and omly divided into a Medicine group ( who received antidepressive drug treatment ) , a Placebo group ( who received placebo ) and a Natural Process group ( who received no treatment ) . The depth of their depression was assessed by Hamilton 's Depressive Rating Scale before the beginning of the trial , on the 14th day and on the 28th day of trial . They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment . The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics , so far as their response to treatment is concerned CONTEXT Acupuncture is widely used to prevent migraine attacks , but the available evidence of its benefit is scarce . OBJECTIVE To investigate the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in patients with migraine . DESIGN , SETTING , AND PATIENTS Three-group , r and omized , controlled trial ( April 2002-January 2003 ) involving 302 patients ( 88 % women ) , mean ( SD ) age of 43 ( 11 ) years , with migraine headaches , based on International Headache Society criteria . Patients were treated at 18 outpatient centers in Germany . INTERVENTIONS Acupuncture , sham acupuncture , or waiting list control . Acupuncture and sham acupuncture were administered by specialized physicians and consisted of 12 sessions per patient over 8 weeks . Patients completed headache diaries from 4 weeks before to 12 weeks after r and omization and from week 21 to 24 after r and omization . MAIN OUTCOME MEASURES Difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after r and omization . RESULTS Between baseline and weeks 9 to 12 , the mean ( SD ) number of days with headache of moderate or severe intensity decreased by 2.2 ( 2.7 ) days from a baseline of 5.2 ( 2.5 ) days in the acupuncture group compared with a decrease to 2.2 ( 2.7 ) days from a baseline of 5.0 ( 2.4 ) days in the sham acupuncture group , and by 0.8 ( 2.0 ) days from a baseline if 5.4 ( 3.0 ) days in the waiting list group . No difference was detected between the acupuncture and the sham acupuncture groups ( 0.0 days , 95 % confidence interval , -0.7 to 0.7 days ; P = .96 ) while there was a difference between the acupuncture group compared with the waiting list group ( 1.4 days ; 95 % confidence interval ; 0.8 - 2.1 days ; P<.001 ) . The proportion of responders ( reduction in headache days by at least 50 % ) was 51 % in the acupuncture group , 53 % in the sham acupuncture group , and 15 % in the waiting list group . CONCLUSION Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control Fifty obese patients with a body mass index greater than 25 kg/m2 were r and omized into 3 groups : control ( C = 19 ) , placebo ( P = 18 ) and dexfenfluramine ( D = 18 ) . A behavioral modification program which included eating habits , exercise , attitudes , social relationships and six steps to lifetime weight control was taught every week . All patients strictly followed the food manual and recorded their behavior , physical activity and food intake every day through 12 weeks . Placebo and dexfenfluramine 30 mg/day were given in a double blind placebo controlled study . The results showed that all 3 groups had significant decreases in rest times and increased activity times ( p < 0.05 ) and significant reductions of the average total daily energy , carbohydrate and fat intake ( p < 0.05 ) . They all lost weight . Mean + /- SEM cumulative weight loss was 8.3 + /- 0.7 kg in group D , 3.3 + /- 1 kg , in group P and 2.9 + /- 0.7 kg , in group C. The mean additional weight loss of 5 kg , and 5.4 kg seen with dexfenfluramine being highly significant ( p < 0.001 ) from group P and C most likely due to increased thermogenesis . Significant ( p < 0.05 ) and gradual reduction of biceps , triceps skinfold and per cent body fat were constantly observed only in the dexfenfluramine group . There were no significant differences among the 3 groups regarding blood pressure , heart rate , hematologic , lipids and biochemical profiles BACKGROUND In Atlanta , as in other major urban areas of the United States , asthma is a leading cause of school absenteeism , emergency department use , and hospitalization . Recent guidelines for asthma management recommend reducing exposure to relevant allergens , but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty . OBJECTIVE We sought to investigate allergen avoidance as a treatment for asthma among inner-city children . METHODS One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested . The children were r and omized to an active avoidance group , a placebo avoidance group , and a second control group for which no house visits occurred until the end of the first year . Avoidance included bed and pillow covers , hot washing of bedding , and cockroach bait . Eighty-five children completed the study , and the outcome was measured as unscheduled clinic visits , emergency department visits , and hospitalization for asthma , as well as changes in mite and cockroach allergen levels . RESULTS There was a significant decrease in acute visits for asthma among children whose homes were visited ( P < .001 ) . However , there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations . When the children with mite allergy were considered separately , there was a significant correlation between decreased mite allergen and change in acute visits ( P < .01 ) . The avoidance measures for cockroach allergen appeared to be ineffective , and the changes observed did not correlate with changes in visits . CONCLUSIONS Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocol s in this environment . The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty . Furthermore , the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population Thirty children were r and omly assigned to one of three groups prior to receiving dental treatment . One third of the children were assigned to a stressinoculation group , one third to an attention control group , and one third to a no-treatment group . The stress-inoculation group received instruction in relaxation and in positive self-talk . Observations by an individual who was blind to treatment condition revealed that children in the stress-inoculation group exhibited fewer body movements and verbalizations during the dental procedure than children in the control groups , p < .05 . The results are interpreted as consistent with several recent experiments showing that very brief psychological interventions can be useful for controlling undesirable reactions to medical and dental procedures PURPOSE To determine both the efficacy and safety of the topical application of 50 mg penicillin G potassium troches ( Cankercillin ) in the treatment of minor recurrent aphthous stomatitis ( RAS ) . STUDY DESIGN The investigation used a phase 2 double-blind , r and omized placebo-controlled trial with a no-treatment arm . Subjects with minor aphthous ulcers of duration < 48 hours were followed for 1 week . The primary endpoint for efficacy was time ( days ) to complete ulcer resolution , and the secondary endpoint was time ( days ) to complete pain relief . RESULTS Thirty-one , 33 , and 36 subjects were r and omized to the active treatment , placebo , and no-treatment arms , respectively . Baseline findings were heterogeneous across arms . Subjects who received penicillin G treatment had complete ulcer healing and pain relief significantly earlier than those in the placebo and no-treatment arms . No allergic reactions were observed . CONCLUSIONS Topical penicillin G , by mechanisms which remain unclear , reduces the time of healing and pain relief of minor aphthous ulcers with minimal safety concerns . Larger phase 3 studies are necessary to confirm these findings The authors sent a question naire to 772 r and omly selected Danish clinicians and asked them about their use of placebo interventions . Sixty-five percent responded . Among the general practitioners , 86 % ( 95 % confidence interval 81 - 91 ) reported to have used placebo interventions at least once , and 48 % ( 41 - 55 ) to have used placebo interventions more than ten times , within the last year . Hospital-based doctors and private specialists reported to have used placebo interventions less frequently ( p < .001 ) . The most important reason for the use of placebo interventions was to avoid a confrontation with the patient . Typical placebos were antibiotics for viral infections . Approximately 30 % ( 28 - 36 ) of the clinicians believed in an effect of placebo interventions on objective outcomes , and 46 % ( 42 - 50 ) found clinical placebo interventions generally ethically acceptable Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available . Ipratropium bromide ( IB ) is an anticholinergic drug that has been shown to decrease gl and ular secretion when applied topically to the nasal mucosa . The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds . Rhinorrhea severity was measured objective ly by determining nasal discharge weights and subjectively by means of visual analog scale scores . Compared with either vehicle or no treatment , IB nasal spray produced a significant decrease in the severity of rhinorrhea . A dose of 84 micrograms ( two sprays of a 0.06 % solution in buffered saline solution ) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose . The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose . None of the adverse events related to intranasal IB therapy was of a serious nature . The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold BACKGROUND Sedative drugs are generally given to patients undergoing colonoscopy . However , the benefit of routinely administered conscious sedation for colonoscopy has not been studied in adequately controlled trials . METHODS We r and omly assigned 180 patients scheduled for diagnostic colonoscopy into 3 groups : ( 1 ) sedation with intravenous midazolam ( midazolam group ) ; ( 2 ) sedation with intravenous saline ( placebo group ) ; and ( 3 ) no intravenous cannula ( control group ) . The endoscopist assessed the procedure immediately after the examination . The patients completed a question naire before leaving the endoscopy unit . Another question naire was sent to the patients 2 weeks after the examination . Answers were mainly given on a 100 mm visual analog scale . RESULTS Shortly after the procedure , the patients in the midazolam group rated the examination less difficult than those in the placebo group ( 30 vs. 40 mm ; p < 0.05 ; visual analog scale , 0 to 100 mm : 0 = not at all , 100 = extremely ) . However , no significant difference was found between midazolam and control groups ( 30 vs. 36 mm , respectively ) . Otherwise , there were no differences between the three groups with respect to the patients ' or endoscopists ' assessment s or the examination time . CONCLUSIONS Routinely administered sedation does not markedly increase patient tolerance or make colonoscopy technically easier Six hundred patients were alloted to one of 4 groups and given : 1 ) no treatment , 2 ) a homeopathic treatment ( Opium and Raphanus ) , 3 ) Opium + a placebo , 4 ) two placebos . This work does not confirm the role of either Opium or Raphanus in the restoration of transit following abdominal surgery Background : Breathlessness is a common and difficult symptom to treat in patients with cancer . Case reports suggest that nebulised furosemide can relieve breathlessness in such patients but few data are available . Method : Patients with primary or secondary lung cancer and a Dyspnoea Exertion Scale score of ⩾3 were recruited . Following familiarisation , patients received either nebulised furosemide 40 mg or nebulised 0.9 % saline under double blind conditions or no treatment , in r and om order on 3 consecutive days . Patients undertook number reading and arm exercise tests to assess breathlessness and its impact , and were asked to report subjective benefit and any preference between nebulised treatments . Results : 15 patients took part . There were no differences between furosemide , saline and no treatment in the outcomes of the number reading test ( eg , mean number read per breath was 6.7 , 6.4 and 6.7 , respectively ) or arm exercise test ( eg , mean Borg score at maximum equivalent workload was 2.3 , 2.5 and 2.7 , respectively ) . No adverse effects were reported , although there was a small fall in forced expiratory volume in 1 s and forced vital capacity following saline . Six patients considered that their breathlessness improved with nebulised treatment , three preferring saline , one furosemide and two reporting they were of equal benefit . Conclusions : Our findings do not support a beneficial effect from nebulised furosemide in patients with cancer related breathlessness . Listed on the National Research Register ( N0170118249 ) and the UK Clinical Research Network Portfolio Data base ( 1428 ) Objective : To investigate the feasibility of conducting a r and omized trial of the effect of acupuncture in decreasing hot flashes in peri- and postmenopausal women . Design : Fifty-six women ages 44 to 55 with no menses in the past 3 months and at least four hot flashes per day were recruited from two clinical centers and r and omized to one of three treatment groups : usual care ( n = 19 ) , sham acupuncture ( n = 18 ) , or Traditional Chinese Medicine acupuncture ( n = 19 ) . Acupuncture treatments were scheduled twice weekly for 8 consecutive weeks . The sham acupuncture group received shallow needling in nontherapeutic sites . The Traditional Chinese Medicine acupuncture group received one of four treatments based on a Traditional Chinese Medicine diagnosis . Usual care participants were instructed to not initiate any new treatments for hot flashes during the study . Daily diaries were used to track frequency and severity of hot flashes . The mean daily index score was based on the number of mild , moderate , and severe hot flashes . Follow-up analyses were adjusted for baseline values , clinical center , age , and body mass index . Results : There was a significant decrease in mean frequency of hot flashes between weeks 1 and 8 across all groups ( P = 0.01 ) , although the differences between the three study groups were not significant . However , the two acupuncture groups showed a significantly greater decrease than the usual care group ( P < 0.05 ) , but did not differ from each other . Results followed a similar pattern for the hot flash index score . There were no significant effects for changes in hot flash interference , sleep , mood , health-related quality of life , or psychological well-being . Conclusions : These results suggest either that there is a strong placebo effect or that both traditional and sham acupuncture significantly reduce hot flash frequency In a double-blind ( patient and evaluator ) , crossover study effects of real acupuncture , simulated acupuncture , nebulized isoproterenol , nebulized saline and no treatment in reversing methacholine-induced bronchospasm were compared in 12 asthmatics ( ages 16 to 64 ) . Saline and simulated acupuncture did not result in any significant improvement in specific airway conductance ( SGaw ) , thoracic gas volume ( Vtg ) or forced expiratory flow rates compared with no treatment following methacholine-induced bronchospasm . Isoproterenol and real acupuncture were both followed by increases in SGaw and flow rates and decreases in Vtg which were significantly different from the changes observed following no treatment , saline or simulated acupuncture , although isoproterenol produced greater improvement than real acupuncture , although isoproterenol produced greater improvement than real acupuncture . These findings suggest that stimulation of specific acupuncture loci reduces methacholine-induced bronchospasm and hyperinflation to an extent greater than can be attributed to placebo phenomena Abstract To examine the potential role for a placebo cream in reducing reported needle pain severity in children , and the impact of age‐related factors on pain self‐report , a convenience sample of 117 children scheduled for venipuncture were r and omly assigned to one of three treatments : ( a ) placebo cream with the suggestion that it might help reduce needle pain , ( b ) placebo cream with no indication as to the cream 's purpose , and ( c ) no cream ( control group ) . In allocation to treatment , children were stratified by age group , ( 3–7 , 8–11 , 12–17 years ) . They rated their needle pain severity ( both predicted and reported ) using the Faces Pain Scale , and rated their anxiety about the procedure using the Children 's Anxiety and Pain Scale . Children in the cream groups were also asked whether they thought the cream had helped . Using video‐tapes , an independent observer , blind to the placebo manipulation , rated each child 's reaction to the needle . For the two groups receiving cream , 83 % of those children told it might help stated that they believed it did , as compared with only 33 % of children who received the cream but were told nothing of its purpose . These beliefs , however , were not reflected in self‐report ratings of pain which showed no statistically significant treatment effect . Similarly , children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream . There was , however , a treatment effect on the observer 's ratings : children receiving cream plus suggestion were assigned significantly lower ratings of pain‐related behaviour than those children who received the cream alone . While venipuncture was associated with only mild levels of pain , younger children , irrespective of treatment group , did report more pain than older children . Hierarchical regression analysis indicated that 60 % of the variance in self‐reported pain severity scores could be accounted for by how much the child thought the needle would hurt , how anxious the child was about receiving the needle , gender ( higher pain ratings associated with girls ) , and estimated body surface area ( higher pain ratings associated with smaller bodies ) . We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se The Sosium-Potassium Blood Pressure Trial in Children ( NaKS ) , is a clinical trial in a healthy , free living population of children and adolescents . It is design ed to test the hypotheses that a reduction in dietary sodium and /or an increase in potassium intake will decrease the rate of rise in blood pressure during normal maturation in children and adolescents with high normal blood pressure . Screening was conducted in 19,452 students in grade s 5 - 8 in Minneapolis and St. Paul between January 1986 and May 1987 . After screening , 3,223 students were found to have blood pressures that fulfilled the initial eligibility criteria for the study , and of these , 643 ( 20.0 % ) attended the orientation meeting , i.e. , the first clinic visit . A total of four clinic visits , design ed to test the willingness and capability of the potential participants to comply with the study protocol were conducted prior to r and omization . At the conclusion of the four prer and omization visits , 243 children ( 7.5 % of the initially eligible children ) agreed to be r and omized to one of four trial groups : low-sodium diet ; potassium supplement administration ; placebo-treated control group ; and a no-treatment control group ( to test the effect of acclimatization on blood pressure measurements ) that will not be seen after r and omization until the 4-year termination of the study . The first participant was r and omized into the study on June 17 , 1986 , and the last on December 29 , 1987 . The potassium and placebo capsules are administered double-masked . Participants will be examined and receive intervention instruction four times yearly for 4 years counted from the date of their r and omization . All groups were comparable with regard to distribution of school district , sex , and race and with respect to baseline physical characteristics . Results from this study will provide information about the feasibility and effect of dietary intervention during childhood and adolescence on the prevention of essential hypertension The authors evaluated the effectiveness of a videotaped behavioral treatment program in reducing dental anxiety . They compared patients who witnessed the intervention videotape with patients who saw a placebo program and with a no-treatment control group . The subjects were 66 patients who visited a dentistry clinic for prophylaxis and general dental treatment . Groups were balanced for gender and level of preference for information as measured by the Krantz Health Opinion Survey -- Information subscale . Self-report , physiological , and observed behavioral measures were assessed at specified times . Results demonstrated significant Group X Gender interaction effects during the different assessment periods , with men responding best to the treatment videotape , whereas women responded best to the placebo videotape . The level of information preference was found to a be a significant contributing factor at certain assessment periods . Overall , these results suggest that preparatory videotaped interventions are particularly effective in decreasing dental anxiety when patient characteristics are matched with characteristics of the intervention Blood-donation-related symptoms such as dizziness and weakness discourage people from participating in this important health-related activity . Four hundred sixty-seven young adult , French-speaking blood donors were r and omly assigned to ( a ) a condition in which they learned a possible preventive technique called applied tension and were asked to practice it from the time they got on the donation chair until they were just about to get up , ( b ) a placebo condition in which they learned applied tension and were asked to practice it from the time they got on the chair until the insertion of the donation needle , or ( c ) a no-treatment control condition . Donors assigned to the treatment condition reported significantly fewer blood-donation-related symptoms than did donors assigned to the other conditions and rated their likelihood of returning to give blood again as greater than did those in the no treatment condition . Among donors whose chairs were not reclined , participants in the treatment condition had significantly smaller heart rate reactions to blood donation than did those in the other conditions It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect , as suggested by the gate control theory . Electrical stimulation ( by way of Interferential Current ) applied at the pain area ( segmental ) was administered to 4 groups of patients with osteoarthritis ( OA ) knee pain . Two groups were administered with noxious stimulation ( 30 % above pain threshold ) and two with innocuous stimulation ( 30 % below pain threshold ) . In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived . Group 5 and 6 received sham stimulation and no treatment , respectively . The outcome measures were : chronic pain intensity , morning stiffness , range of motion ( ROM ) , pain threshold and % pain reduction . Both noxious and innocuous stimulation significantly decreased chronic pain ( P<0.001 ) and morning stiffness ( P<0.01 ) and significantly increased pain threshold ( P<0.001 ) and ROM ( P<0.001 ) compared with the control groups . Nevertheless , noxious stimulation decreased pain intensity ( P<0.05 ) and increased pain threshold ( P<0.001 ) significantly more than innocuous stimulation . No differences in treatment outcomes were found between adjusted and unadjusted stimulation . ( a ) Interferential current is very effective for chronic OA knee pain , ( b ) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation , ( c ) the fading of sensation during treatment , does not decrease the analgesic effect . Possible mechanisms explaining the findings are discussed A double-blind study was carried out in 18 patients with biliary and pancreatic disease to assess the use of pinaverium bromide in premedication for endoscopic retro grade cholangio-pancreatography and its effects on motor activity of the sphincter of Oddi . Patients were divided at r and om into three groups . One group received 100 mg pinaverium bromide twice daily for 3 days before and then 100 mg 1 hour before the examination , the second group received placebo , and the third had no medication . All patients received 10 to 20 mg diazepam intravenously 10 minutes before endoscopy . Assessment s were made of the transit time of various endoscopic phases and patients ' tolerance of the procedure . The effects of treatment on the sphincter of Oddi were estimated by means of endoscopic manometry . The results showed that pinaverium bromide allowed transit time reduction in endoscopic procedure , a greater tolerance on the part of the patient and marked reduction in the amplitude and duration of the phasic activity of the sphincter This experiment examined the efficacy of an acustimulation wrist b and for the relief of chemotherapy-induced nausea using a r and omized three-arm clinical trial ( active acustimulation , sham acustimulation , and no acustimulation ) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment . Five outcomes related to wrist b and efficacy ( acute nausea , delayed nausea , vomiting , QOL , and total amount of antiemetic medication used ) were examined . The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea . There were no significant differences in any of these study measures among the three treatment conditions ( P>0.1 for all ) . Study results do not support the hypothesis that acustimulation b and s are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients OBJECTIVES We sought to determine the efficacy of coaching Latino adolescents with latent tuberculosis infection to adhere to isoniazid treatment . METHODS Participants ( n = 286 ) were r and omly assigned to adherence coaching , attention control , or usual care groups . Adherence was measured via interviews and vali date d with urine assays . RESULTS Coaching result ed in significant increases in adherence compared with attention and usual care groups . Bicultural adolescents were more likely to be adherent than those most or least acculturated . Age and risk behavior were negatively related to adherence . CONCLUSIONS Coaching can increase Latino adolescents ' adherence to treatment for latent tuberculosis infection and should contribute to tuberculosis control for adolescents at high risk of contracting the disease OBJECTIVE Synergy has been proposed between modalities operating at different levels of action . Acupuncture and craniosacral therapy are two very different modalities for which synergy has been proposed . This study sought to test for such synergy and to determine if complementary therapies would improve pulmonary function and quality of life for people suffering from asthma , as well as reducing anxiety , depression , and medication usage . DESIGN Subjects were r and omly assignment to one of five groups : acupuncture , craniosacral therapy , acupuncture and craniosacral , attention control , and waiting list control . METHODS Subjects received 12 sessions of equal length with pretreatment and posttreatment assessment of pulmonary function , asthma quality of life , depression , and anxiety . Medication use was also assessed . RESULTS Synergy was not demonstrated . When treatment was compared with the control group , statistically treatment was significantly better than the control group in improving asthma quality of life , whereas reducing medication use with pulmonary function test results remained the same . However , the combination of acupuncture and craniosacral treatment was not superior to each therapy alone . In fact , although all active patients received 12 treatment sessions , those who received all treatments from one practitioner had statistically significant reductions in anxiety when compared with those receiving the same number of treatments from multiple practitioners . No effects on depression were found . CONCLUSIONS Acupuncture and /or craniosacral therapy are potentially useful adjuncts to the conventional care of adults with asthma , but the combination of the two does not provide additional benefit over each therapy alone The effectiveness of various tension-reducing techniques was investigated . Sixty-three subjects were r and omly assigned to four treatment groups ( EMG feedback , finger temperature feedback , EMG plus finger temperature feedback , autogenic training ) , a placebo control group , and a waiting-list control group . Physiological as well as a variety of cognitive measures were used to monitor changes in tension . The results showed no significant difference in effectiveness between the six groups . On virtually all cognitive measures there were significant decreases in tension , but not on the physiological measures . The decreases in tension on the cognitive measures were interpreted to be the results of non-specific ( placebo ) effects . These non-specific effects were not short-term , but did persist for at least three months after completion of treatment Objective To investigate whether placebo effects can experimentally be separated into the response to three components— assessment and observation , a therapeutic ritual ( placebo treatment ) , and a supportive patient-practitioner relationship— and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome . To assess the relative magnitude of these components . Design A six week single blind three arm r and omised controlled trial . Setting Academic medical centre . Participants 262 adults ( 76 % women ) , mean ( SD ) age 39 ( 14 ) , diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale . Interventions For three weeks either waiting list ( observation ) , placebo acupuncture alone ( “ limited ” ) , or placebo acupuncture with a patient-practitioner relationship augmented by warmth , attention , and confidence ( “ augmented ” ) . At three weeks , half of the patients were r and omly assigned to continue in their originally assigned group for an additional three weeks . Main outcome measures Global improvement scale ( range 1 - 7 ) , adequate relief of symptoms , symptom severity score , and quality of life . Results At three weeks , scores on the global improvement scale were 3.8 ( SD 1.0 ) v 4.3 ( SD 1.4 ) v 5.0 ( SD 1.3 ) for waiting list versus “ limited ” versus “ augmented , ” respectively ( P<0.001 for trend ) . The proportion of patients reporting adequate relief showed a similar pattern : 28 % on waiting list , 44 % in limited group , and 62 % in augmented group ( P<0.001 for trend ) . The same trend in response existed in symptom severity score ( 30 ( 63 ) v 42 ( 67 ) v 82 ( 89 ) , P<0.001 ) and quality of life ( 3.6 ( 8.1 ) v 4.1 ( 9.4 ) v 9.3 ( 14.0 ) , P<0.001 ) . All pairwise comparisons between augmented and limited patient-practitioner relationship were significant : global improvement scale ( P<0.001 ) , adequate relief of symptoms ( P<0.001 ) , symptom severity score ( P=0.007 ) , quality of life ( P=0.01 ) . Results were similar at six week follow-up . Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a grade d dose escalation of component parts . Non-specific effects can produce statistically and clinical ly significant outcomes and the patient-practitioner relationship is the most robust component . Trial registration Clinical Trials NCT00065403 We tested the hypothesis that antihistamine-decongestant combinations cause no clinical ly significant relief of the symptoms of upper respiratory tract infections in young children by r and omly assigning 96 children to one of three treatment groups : antihistamine-decongestant , placebo , and no treatment . There were no differences among the three study groups in the proportion of children considered " better " overall by the parent 48 hours after the initial assessment ( drug , 67 % ; placebo , 71 % ; no treatment , 57 % ; p = 0.53 ) . There were no differences among groups in individual or composite symptom score changes . Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms . In the proportion of parents believing that their child needed medicine , there was no difference between those who consented to participate and those who refused . Parents who wanted medicine at the initial visit reported more improvement at follow-up , regardless of whether the child received drug , placebo , or no treatment . We conclude that there is no clinical ly significant improvement in symptoms of upper respiratory tract infection , including no significant placebo effect , in young children for whom an antihistamine-decongestant is prescribed Background : Acupuncture and acupressure have previously been reported to possess antiemetic effect . We wanted to investigate the “ true ” and placebo effect of acupressure in prevention of postoperative nausea and vomiting ( PONV ) Rhinorrhea , nasal congestion , and sneezing are the cardinal symptoms of common colds . The pathogenesis of these symptoms is incompletely understood , and currently available therapies are largely ineffective in ameliorating rhinorrhea [ 1 ] . Because histologic studies have indicated that rhinoviral infection causes little direct damage to the nasal mucosa , it has been hypothesized that the pathogenesis of cold symptoms is related to host responses and involves the release of inflammatory mediators and neurogenic reflexes [ 2 - 5 ] . The rhinorrhea associated with common colds is multifactorial and involves both transudation of plasma proteins and increased secretion by the submucosal gl and s of the nose [ 6 ] ; secretion by the submucosal gl and s increases after the intranasal application of cholinergic agents [ 7 ] and through parasympathetic nervous system reflex mechanisms . The intranasal administration of anticholinergic agents , particularly ipratropium bromide and atropine methonitrate , has been associated with reduced nasal mucus production during experimentally induced rhinovirus colds [ 8 - 10 ] . In addition , methacholine-induced rhinorrhea can be prevented by the topical application of ipratropium [ 11 ] or atropine [ 12 ] . Initial clinical trials [ 13 , 14 ] found that intranasal sprays of ipratropium bromide ( 84 g per nostril three or four times daily ) also reduced the rhinorrhea associated with naturally occurring colds . However , excessive drying related to the topical application of anticholinergic agents may worsen certain symptoms , such as nasal obstruction , without providing an overall clinical benefit . Consequently , we did this study to determine the efficacy and tolerability of intranasal ipratropium bromide for the treatment of common colds with regard to the effect of this therapy on the patient 's overall perception of well-being and on subjective and objective measures of rhinorrhea . Methods Study Design This was a multicenter , double-blind , r and omized , placebo-controlled trial . For the purpose s of comparison , it incorporated a group of untreated patients that was monitored in the same way as the ipratropium and control groups . The trial involved 411 persons who had self-diagnosed common colds and were enrolled at one of three study centers . To avoid the autumn and spring allergy seasons , patients were enrolled between 1 November 1993 and 29 March 1994 . Study Participants Patients were recruited by advertisement and were compensated for participation . Male and female patients 12 to 70 years of age who had had rhinorrhea associated with a common cold for no more than 36 hours were eligible . The rhinorrhea had to be scored as at least moderate in severity ( a score of 5 or more on a visual analogue scale ) , and the severity had to be confirmed by the recovery of at least 1.5 g of nasal discharge over a 1-hour baseline observation period . For each participant , a medical history was taken and nasal and limited physical assessment s , which included measurement of vital signs , were done at the time of study entry . Persons with a history of asthma or chronic respiratory disease , allergic or perennial rhinitis , nasal polyps , seasonal allergic rhinitis with allergen in season , or frequent complications associated with upper respiratory infections ( such as sinusitis or bronchitis ) were excluded , as were pregnant and lactating women . Patients with a positive result on a streptococcal antigen screening test ( Q-Test-Strep , Becton-Dickinson , Cockeysville , Maryl and ) , signs of lower respiratory tract disease , or an oral temperature greater than 102 F were also excluded from participation . Written informed consent was obtained from each patient in a form approved by the institutional review board of each study institution . Treatment Administration Patients who met the entrance criteria were r and omly assigned by a computer-generated r and omization sequence to one of three groups : that receiving ipratropium bromide nasal spray 0.06 % in a buffered salt solution ( two sprays per nostril , administered with a metered pump spray bottle design ed to deliver a total dose of 84 g per nostril ) ; that receiving control nasal spray , which contained the same excipients as the ipratropium bromide spray but did not contain ipratropium bromide ; or that receiving no treatment . The patients were instructed to clear their noses and administer two sprays in each nostril three times daily for 4 days at equally spaced intervals during waking hours . The protocol allowed patients to use their medication four times daily if rhinorrhea was not adequately controlled or fewer than three times daily if nasal dryness occurred . The patients were consecutively enrolled at each study center , and r and omization was done in blocks of six . The treatments were administered under double-blind conditions ; the untreated group was not blinded . The ipratropium and control spray bottles were identical in appearance . To minimize unintentional bias in assigning patients to receive no treatment , empty bottles were used as place holders for these patients . The bottles were placed in sequence with the filled bottles and were labeled Do Not Dispense to Patient . Throughout the study , patients were instructed to take no other medications ( such as antihistamines , decongestants , nasal decongestants or steroids , or saline nose drops ) to relieve their nasal symptoms . Analgesics ( including acetaminophen , aspirin , and ibuprofen ) and antitussives ( Robitussin or Robitussin-DM ; A.H. Robbins Co. , Richmond , Virginia ) were allowed for the relief of disabling symptoms . Clinical Monitoring After baseline monitoring and the administration of the first nasal spray treatment , patients remained at the study center for 6 hours . During this period , they provided hourly evaluations of the severity of their rhinorrhea and hourly collection s of expelled nasal mucus . A visual analogue scale was used to evaluate symptom severity . This scale ranged from 0 to 10 and included five descriptions of severity : very mild ( doubtful , trivial , or just noticeable ) , mild ( present but not uncomfortable ) , moderate ( present and somewhat uncomfortable or annoying ) , severe ( present and definitely uncomfortable or annoying ) , and unbearable ( necessitating additional treatment ) . On study day 2 , the patients returned to the study center before taking their first dose of medication or at least 4 hours after taking any dose . After receiving ipratropium , control spray , or no treatment , they evaluated the severity of their rhinorrhea and provided expelled nasal mucus every hour for 3 hours . On the evenings of study days 1 through 4 , all patients completed daily symptom record forms evaluating the overall severity of runny nose , nasal congestion , and sneezing for that day . On each of the 2 testing days , the patients were asked a single global question : Compared to when you came into the clinic this morning , how was your cold over today 's testing period ? One of four categorical responses ( much better , better , no difference , or worse ) was recorded . On study days 3 and 4 , the patients continued their treatment on an outpatient basis and then returned to the study center on study day 5 for follow-up examination , collection of study records and spray devices , and completion of final global assessment s. On study day 5 , patients were asked , Overall , how do you think being in this study helped your cold ? and Overall , how was this treatment in the relief of your symptoms ? Data Analysis The data for all patients who were r and omly assigned to treatment groups and who received at least one dose of their treatment were included in the analysis [ 410 of 411 patients ] . The primary end point used to determine efficacy was the patient 's global assessment of overall improvement obtained on study days 1 , 2 , and 5 . Secondary measures of efficacy included 1 ) quantitation of nasal discharge weights and subjective assessment s of rhinorrhea severity on the first 2 study days and 2 ) assessment of the severity of cold symptoms made using the visual analogue scale on the evening of each of the first 4 study days . The distribution of responses to each global question by study group was assessed . The stratified Wilcoxon test was the primary method of analysis used for the global assessment s. To assess rhinorrhea using the visual analogue scale , we subtracted the hourly scores after treatment from the baseline values and determined the hourly average change from baseline . The end points were the average change from baseline for each of the first two study days and the average change from baseline for the first 3 hours on each of these 2 days combined . These data were analyzed using an analysis of variance that incorporated the centers and treatment-by-center interactions as factors . Baseline nasal mucus weights were used as a covariate in the analysis of discharge weights . The daily visual analogue scale assessment s of rhinorrhea , nasal congestion , and sneezing were analyzed in a similar way but without a baseline covariate . Adverse events were recorded as they occurred , but we did not specifically ask about them . Staff members asked each patient how he or she had felt since the previous visit . Nasal examinations were done and vital signs were obtained on study day 1 and at the final study visit . The sample size for this trial was determined on the basis of global assessment s that required the patients to choose one of four ordinal categories ( much better , better , no difference , or worse ) to describe the amelioration or lack of amelioration of their cold . By comparing the percentage of patients in the ipratropium group who chose either much better or better with the percentage of patients in the control group who chose these responses , we determined that a sample size of 130 patients per group would be sufficient to detect 20 % differences in proportions ranging from 20 % versus 40 % to 70 % versus 90 % between the control and ipratropium groups , respectively , with a 90 % Postoperative nausea and vomiting ( PONV ) is one of the most common postoperative complications . Aside from pharmacological interventions , other complementary healing modalities have been introduced to assist patients in decreasing PONV and improving postoperative outcomes . This study examined acupressure as a potentially holistic and safe complement to the more traditional approach of using drugs to prevent and /or relieve nausea and vomiting in the postoperative patient . Acupressure involves constant pressure ( without puncture of the skin ) on the Nei Guan acupuncture points through the use of a British product called Sea-B and s ( Sea B and UK Ltd , Leics , Engl and ) . These b and s are made of elasticated fabric , with a small round plastic button inside . A quasi-experimental research design was used to examine the effects of unilateral and bilateral application of acupressure on 157 patients who are prone to PONV : postgynecological , postplastic , and posturological surgery patients . The incidence of PONV was determined through retrospective chart review s. The hypothesis was that there would be a difference in the incidence of PONV between 5 groups : group 1 ( Sea-B and s with acupressure on both wrists ) , group 2 ( Sea-B and s with acupressure on one wrist ) , group 3 ( wristb and without acupressure on both wrists ) , group 4 ( wristb and without acupressure on one wrist ) , and group 5 ( no wristb and ) . This hypothesis was examined by using a one-way analysis of variance ( ANOVA ) ; it was not supported . Neither unilateral nor bilateral application of acupressure significantly affected the incidence of nausea and vomiting . These findings must be viewed with caution , however , because power analysis showed low effect sizes and an inadequate sample size . Further research is recommended with a larger sample size . This study has made perianesthesia nurses more aware of other complementary modalities to assist patients with nausea and vomiting Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives ( mean age 38 + /- 10 yrs , 13 males and 9 females ) . After the first baseline monitoring , the patients were r and omised , according to a cross-over design , to one of the following sequences : no therapy to placebo or placebo to no therapy . At the end of each period , noninvasive ambulatory monitoring was performed . Mean + /- SE 24 h systolic ( SBP ) and diastolic ( DBP ) pressures recorded at the first monitoring were 129.2 + /- 3.5 mmHg and 81.7 + /- 2.3 mmHg respectively . At the second and third monitorings , mean 24 h BP differences versus baseline levels were -2.9 + /- 1.8 and -4.7 + /- 1.7 mmHg for SBP , and -2.0 + /- 1.1 and -2.7 + /- 1.5 mmHg for DBP . Both SBP and DBP differences at repeated monitorings were significant by analysis of variance ( P less than 0.05 ) . No significant effects on BP of treatment sequence or of placebo administration were found . Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences ( SBP : beta = -0.260 , DBP : beta = -0.124 ) . ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours . Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of ' white coat'-induced BP increase only for DBP ( P = 0.022 ) . For both 24 h SBP and DBP , however , a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed . It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect . Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different The results of a clinical outcome study ( N = 57 ) comparing behavior therapy directed at panic disorder ( panic control treatment [ PCT ] ) with alprazolam were reported . These conditions were compared with a medication placebo and a waiting-list control group . Patterns of results on measures of panic attacks , generalized anxiety , and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures . The alprazolam group differed significantly from neither PCT nor placebo . The percentage of clients completing the study who were free of panic attacks following PCT was 87 % , compared with 50 % for alprazolam , 36 % for placebo , and 33 % for the waiting-list group . Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment , these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder 45 patients suffering from severe chronic intermittent headaches were divided into 3 groups matched for sex , and assigned to a double-blind 5-week cross-over design with 3 X 1 g/d metamizole -- a mild analgesic of the pyrazolone type -- a placebo , or a no-treatment control condition . For each of the 6 sessions ( t0-t5 ) signal detection theory parameters d ' and log beta for assessment of electrical pain perception and headache ratings on the preceding treatment period were obtained . At t0 all patients were examined via a personality inventory . There were no significant drug effects on headache and signal detection theory parameters , but a clear decrease of the discrimination index d ' and of clinical pain over time , regardless of the mode of treatment . No relationship between pathological and experimentally induced pain could be demonstrated . There was no significant negative correlation between response bias of judgement of stimulus intensity ( log beta ) and neuroticism The relationship between past medical experience and children 's response to preparation for medical examinations was investigated in 79 pediatric out patients aged 3 to 12 years . Children were r and omly assigned to one of five preparation conditions prior to receiving a medical examination and a throat culture : sensory information about the exam , training in coping skills ( deep breathing and positive self-talk ) , combined sensory information and coping skills training , attention control , and no-treatment control . The results indicated that children with previous negative medical experiences demonstrated more behavioral distress during a throat culture examination that did children with previous positive or neutral medical experiences . In addition , the attention control condition appeared to increase the distress of children with previous negative medical experiences . Amount of past exposure to the specific medical procedure was not related to observed distress . The implication s of these findings for the preparation of children for medical procedures are discussed Previous studies show that uridine 5'-triphosphate ( UTP ) , a P2Y(2 ) receptor agonist , is effective at acutely enhancing mucociliary clearance in healthy , nonsmoking adults . UTP solution for inhalation is being developed by Inspire Pharmaceuticals under the compound number INS316 . In a double-blind , r and omized , crossover , placebo-controlled study we tested the single-dose effect of UTP in chronic smokers with mild chronic bronchitis ( n = 15 ) by measuring the clearance of (99m)Tc-Fe(2)O(3 ) particles ( 4.0 microm mass median aerodynamic diameter [ MMAD ] ) after inhalation of nebulized placebo ( 0.9 % saline ) and two doses of UTP ( 20 and 100 mg in the nebulizer ) . On each study day , gamma camera scanning was performed over a 2-h period . After an initial deposition scan , subjects inhaled placebo or UTP during the first 20 min of scanning . Analysis of whole lung clearance showed that the retention-time curves for each day were biphasic and that the earliest break point in the average curves occurred at 50 min . Mean particle clearance rate ( Clr in % /min ) through 50 min for placebo treatment was Clr = 0.65 + /- 0.27 whereas treatment with UTP showed Clr significantly increased to 0.95 + /- 0.48 and 0.93 + /- 0.44 for the 20-mg and 100-mg dose respectively , p < 0.005 for both as compared with placebo . These data show that mucociliary clearance associated with mild chronic bronchitis is acutely improved with minimal doses of aerosolized UTP , presumably because of its stimulation of ciliary beating and hydration of airway secretions BACKGROUND Cardiorespiratory events during colonoscopy are common . The effect of sedative premedication on cardiorespiratory parameters during colonoscopy has not been studied in controlled , prospect i ve trials . METHODS One hundred eighty patients undergoing colonoscopy were divided into 3 groups : ( 1 ) sedation with intravenous midazolam ( midazolam group ) ; ( 2 ) sedation with intravenous saline ( placebo group ) ; and ( 3 ) no intravenous cannula ( control group ) . Arterial oxygen saturation ( SaO(2 ) ) , systolic and diastolic blood pressure and continuous electrocardiogram were recorded prior to , during and after the endoscopic procedure . RESULTS Midazolam produced lower SaO(2 ) values during colonoscopy compared with placebo or control groups ( p < 0.001 , repeated measures analysis of variance ) . Systolic and diastolic blood pressure during colonoscopy were lower in the midazolam group than in the placebo group ( p < 0.01 and p < 0.05 , respectively ) , but no difference was found between the midazolam and the control groups . Hypotension ( systolic blood pressure less than 100 mm Hg ) occurred more frequently in the midazolam group ( 19 % ) than in the placebo ( 3 % ; p < 0.01 ) or control groups ( 7 % ; p < 0.05 ) . ST-segment depression developed in 7 % of patients during the recording with no difference between the groups . In 75 % of cases ST-depression appeared prior to the endoscopic procedure . CONCLUSIONS Premedication with midazolam induced a statistically significant decrease in arterial oxygen saturation and increased the risk for hypotension . However , colonoscopy proved to be a safe procedure both with and without sedation & NA ; The purpose of this study was to investigate whether placebo analgesia is mediated by the release of beta‐endorphin . In addition to subjective pain reports , we included an objective physiological parameter of nociception reflected by the opioid sensitive nociceptive R‐III reflex . Placebo consisted of strong suggestions of pain relief and an intravenous injection of saline . Forty minutes after placebo , either the opioid antagonist naloxone or saline was administered intravenously without subjects noticing ( hidden ) . Sixty healthy males , aged 18–30 years , voluntarily participated in this study . Subjects were r and omized into one of four groups : group 1 received placebo and hidden naloxone , group 2 received hidden naloxone only , group 3 received placebo and hidden saline and group 4 received hidden saline only . Pain was induced by electrical stimulation of the sural nerve and evaluated with a visual analogue scale ( VAS ) . In addition , changes in the magnitude of the nociceptive R‐III reflex activity were assessed . We determined to what extent R‐III reflex activity and subjective pain reports were decreased by placebo and we investigated whether these placebo‐induced changes in reflex activity and subjective pain reports were naloxone reversible . Furthermore , we measured the degree of association between pain relief as measured on VAS and changes in R‐III reflex activity . Finally , the role of beta‐endorphin was assessed by measuring plasma endorphin levels before and after the administration of placebo . This study could not demonstrate a placebo effect as measured on VAS and R‐III responses . The administration of placebo did not appear to have an effect on the release of beta‐endorphins . Consistently , the antagonizing effects of naloxone were negligible . A subgroup analysis of those who did show a placebo response as indicated on the VAS did not support the supposition that beta‐endorphin is released due to placebo suggestion . It is suggested that intensified stimuli and a more effective procedure to induce placebo analgesia ( e.g. conditioning ) may produce a proper placebo effect A 4 week , double blind clinical trial was conducted to assess the antiplaque/anticalculus activity of test dentifrices containing varying levels of zinc citrate . Subjects were divided into 6 groups , 4 experimental , 1 positive control and a placebo group . All subjects only brushed at home using the placebo control during study weeks 1 and 3 . Plaque and calculus were collected at the end of study weeks 2 and 4 on mylar strips worn on lower incisor teeth . Dentifrice efficacy was assessed by comparing group dry and ash weight decrements . While there were no significant differences between the test and control groups , there was a demonstrable trend toward greater inhibition with higher zinc citrate levels , especially among subjects with high levels of plaque and calculus at baseline OBJECTIVE To establish the short term clinical and urodynamic effect of transurethral microwave thermotherapy ( TUMT ) in men with symptomatic uncomplicated benign prostatic hyperplasia ( BPH ) using a r and omized controlled trial comparing the treatment with both ' placebo-like ' and untreated control groups . PATIENTS AND METHODS The study comprised 120 symptomatic patients with BPH who were c and i date s for transurethral resection and TUMT . They were r and omized to one of three groups : group 1 underwent a st and ard TUMT , group 2 underwent a simulated treatment identical to group 1 but with no emission of microwaves and group 3 received no treatment . The treatment of the first two groups was ' double-blind ' and the heat experienced by the patients during treatment was simulated in both . Patients were assessed on entry to the study and 6 months after treatment using an identical protocol to measure the American Urological Association ( AUA ) symptom score , maximum urinary flow rate ( Qmax ) , post-void residual urine volume ( PVR ) , minimum urethral opening pressure ( Pmuo ) and maximum detrusor pressure ( Pdet max ) . RESULTS In the untreated group there were no clinical ly or statistically significant changes in the median AUA symptom score , Qmax , PVR , Pmuo and Pdet max . In group 1 the AUA score changed significantly , from 19 to 9.5 , but the Qmax , PVR , Pmuo and Pdet max did not . In group 2 , the AUA score also changed significantly , from 17.5 to 9.5 , but Qmax , PVR , Pmuo and Pdet max did not . CONCLUSION The untreated control group showed no clinical ly relevant deterioration or improvement . The st and ard and simulated TUMT groups showed little clinical ly relevant improvement in ' objective ' variables , while the clinical ly significant symptom improvement was of a similar magnitude in both groups We evaluated whether , among hyperactive children who required maintenance stimulant treatment , cognitive training enhanced academic performance ; improved the functioning of youngsters who had only a partial behavioral response to medication ; facilitated withdrawal of stimulant treatment ; and enhanced maintenance effects of academic gains following termination of stimulants . A 16-week cognitive training program that emphasized reflective problem-solving strategies and social problem-solving skills was compared with an attention control treatment and with no training . There was virtually no evidence of efficacy of cognitive training . No significant treatment effects were obtained on academic , behavioral , and cognitive measures . Cognitive training did not improve behavior among children with residual problems , nor did it facilitate the withdrawal of medication . With placebo substitution , the overwhelming majority of children required remedication , regardless of previous exposure to cognitive training Sedating children safely and effectively for minor laceration repair is a well-recognized clinical problem . A r and omized , double-blind , and controlled study was conducted to evaluate the efficacy of intranasal midazolam for reducing stress during the suturing of lacerations in preschool children . Fifty-nine children with simple lacerations that required suturing were r and omly assigned to one of three groups . Group 1 received intranasal midazolam , 0.4 mg/kg , prior to suturing . Group 2 received an equivalent volume of normal saline intranasally prior to suturing as a placebo . Group 3 was the control group and received no intervention prior to suturing . Heart rate , respiratory rate , blood pressure , and pulse oximetry were monitored at 5-minute intervals throughout the procedure . Subjective variables were also measured at 5-minute intervals and included a cry score , a motion score , and a struggle score . Parent satisfaction was measured via a short telephone interview the following day . There were no significant differences in outcome between the placebo group and the control group . Their results were pooled and compared with the results for the midazolam group . The midazolam group showed significant reductions for mean heart rate , maximum heart rate , and maximum systolic blood pressure when compared with the placebo/control group . Scores for two of the three subjective variables , cry and struggle , were significantly reduced for the midazolam group . The papoose board was considered unnecessary in retrospect for more than half of patients in the midazolam group compared with only one fifth of patients in the placebo/control group . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Approximately 80 % of nursing home residents who suffer from Alzheimer 's disease and related dementia develop behavioral symptoms of dementia . Given the deleterious side effects of pharmacologic therapy in this population there is an urgent need for clinical trials of nonpharmacologic interventions . OBJECTIVE To examine the effect of therapeutic touch on the frequency and intensity of behavioral symptoms of dementia . METHOD A r and omized , double-blind , three-group experimental study : experimental ( therapeutic touch ) , placebo ( placebo therapeutic touch ) , and control ( usual care ) . Fifty-seven residents , aged 67 to 93 years , exhibiting behavioral symptoms of dementia , were r and omized to one of the three groups within each of three Special Care Units within three Long-Term Care facilities in a western Canadian province . Behavioral observation was completed every 20 minutes from 8:00AM to 6:00PM for three days pre-intervention and for three days post-intervention by trained observers who were blind to group assignment . The intervention consisted of therapeutic touch given twice daily for 5 - 7 minutes for three days between 10:00AM and 11:30PM and between 3:00PM and 4:30PM ( N = 57 ) . The main outcome variable was overall behavioral symptoms of dementia , consisting of six categories of behaviors : manual manipulation ( restlessness ) , escape restraints , search ing and w and ering , tapping and banging , pacing and walking , and vocalization . RESULTS Analysis of variance ( ANOVA ) ( F = 3.331 , P = .033 ) and the Kruskal-Wallis test ( chi2 = 6.661 , P = .036 ) indicated a significant difference in overall behavioral symptoms of dementia , manual manipulation and vocalization when the experimental group was compared to the placebo and control groups . The experimental ( significant ) was more effective in decreasing behavioral symptoms of dementia than usual care , while the placebo group indicated a decreasing trend in behavioral symptoms of dementia compared to usual care . CONCLUSIONS Therapeutic touch offers a nonpharmacological , clinical ly relevant modality that could be used to decrease behavioral symptoms of dementia , specifically manual manipulation ( restlessness ) and vocalization , two prevalent behaviors An exercise for medical students was design ed to illustrate one method of setting up a clinical trial and incidentally to demonstrate some effects of placebos . Twelve groups of four students participated : one in each group was the " recorder " , the other three ( volunteers ) were r and omly assigned to the treatment A , treatment B , or untreated groups . Subjects performed seven psychomotor or mental tests before taking medication and 30 and 60 minutes after medication . The time taken for the tests and the errors made were recorded . Treatment A was one green and yellow gelatin capsule filled with lactose , taken with water ; treatment B was a red and white capsule containing lactose ; untreated subjects received a drink of water . No large changes in performance occurred and no evidence of fatigue or learning was noted , although the B 's took significantly longer to perform the arithmetic test after medication than before . Treated subjects were instructed to check any of 29 listed side effects that they experienced . A total of 44 side effects was reported : 8 of 12 in A group and 10 of 12 in B checked one or more symptoms . Indications are that the results of the trial will not soon be forgotten Exposure to high allergen levels in early life is a risk factor for the development of allergy . We previously reported limited effects of mite allergen impermeable mattress covers in the prevention and incidence of asthma and mite allergy ( PIAMA ) cohort at the age of 1 and 2 yr . We now present the results of follow-up at 4 yr objectives . To examine the effects of early reduction of house dust mite ( HDM ) allergen exposure by means of mattress covers on the incidence of allergy and asthma symptoms in the PIAMA birth cohort at the age of 4 yr . High-risk children ( allergic mother ) were prenatally recruited and r and omly allocated to three groups ; receiving mite allergen impermeable mattress covers ( n = 416 ) , placebo covers ( n = 394 ) or no intervention ( n = 472 ) . At 4 yr of age , atopy was assessed by question naire ; specific Immunoglobulin E ( IgE ) to inhalant and food allergens was measured in serum . Dust sample s collected from the children 's mattresses were analysed for mite allergens . Dermatophagoides farinae1 allergen ( Der f 1 ) levels in dust were reduced in the active group . However , Dermatophagoides pteronissinus 1 ( Der p 1 ) levels , sensitization and atopic symptoms were similar in all groups . We found no effect of mite allergen impermeable mattress covers on sensitization and atopy at 4 yr . Moreover , the allergen reducing effects of the covers had disappeared for one of the two mite allergens that were measured OBJECTIVE To evaluate the effectiveness of h and warming biofeedback ( HWB ) and stress management training in comparison to attention ( h and cooling , HCB ) and wait-list control groups . Thermal biofeedback has been used in many pediatric migraine treatment studies and has demonstrated a consistent therapeutic effect . No published studies to date have compared this treatment modality with credible attention control using biofeedback technology . METHODS Thirty-six children and adolescents ( mean age : 12.8 years ) , as well as the mothers and fathers of these children enrolled in the study , were r and omly assigned to the three groups . Thirty-four children completed treatment . Both treatment groups received four sessions of biofeedback training and a portable biofeedback device for home practice . Ratings of treatment credibility showed that the children rated the two treatments as equally credible . Assessment included anxiety and depression question naires for the children and both of their parents . RESULTS Children who had been assigned to the HWB group were more likely to achieve clinical improvement in migraine after treatment than the children in the HCB group . Treatment gains were maintained up to 6 months after treatment . Home practice data reflected a general increase in temperature in the HWB group and a decrease in temperature for the HCB group . CONCLUSIONS The results of this study confirm the findings of earlier pediatric migraine biofeedback treatment studies and also provide support for the specific effect of treatments including stress management and HWB . Future studies with larger sample sizes will aid in delineating the appropriateness of HCB as a control treatment We conducted a controlled , blinded , multicenter study of disulfiram treatment of alcoholism in 605 men r and omly assigned to 250 mg of disulfiram ( 202 men ) ; 1 mg of disulfiram ( 204 men ) , a control for the threat of the disulfiram-ethanol reaction ; or no disulfiram ( 199 men ) , a control for the counseling that all received . Bimonthly treatment assessment s were done for one year . Relative/friend interviews and blood and urine ethanol analyses were used to corroborate patients ' reports . There were no significant differences among the groups in total abstinence , time to first drink , employment , or social stability . Among the patients who drank and had a complete set of assessment interviews , those in the 250-mg disulfiram group reported significantly fewer drinking days ( 49.0 + /- 8.4 ) than those in the 1-mg ( 75.4 + /- 11.9 ) or the no-disulfiram ( 86.5 + /- 13.6 ) groups . There was a significant relationship between adherence to drug regimen and complete abstinence in all groups . We conclude that disulfiram may help reduce drinking frequency after relapse , but does not enhance counseling in aiding alcoholic patients to sustain continuous abstinence or delay the resumption of drinking Untreated pain during the transportation of patients after minor trauma is a common problem in emergency medicine . Because paramedics usually are not allowed to perform invasive procedures or to give drugs for pain treatment , a noninvasive , nondrug-based method would be helpful . Acupressure is a traditional Chinese treatment for pain that is based on pain relief followed by a short mechanical stimulation of specific points . Consequently , we tested the hypothesis that effective pain therapy is possible by paramedics who are trained in acupressure . In a double-blinded trial we included 60 trauma patients . We r and omly assigned them into three groups ( “ true points , ” “ sham-points , ” and “ no acupressure ” ) . An independent observer , blinded to the treatment assignment , recorded vital variables and visual analog scales for pain and anxiety before and after treatment . At the end of transport , we asked for ratings of overall satisfaction . For statistical evaluation , one-way analysis of variance and the Scheffé F test were used . P < 0.05 was considered statistically significant . Morphometric and demographic data and potential confounding factors such as age , sex , pain , anxiety , blood pressure , and heart rate before treatment did not differ among the groups . At the end of transport we found significantly less pain , anxiety , and heart rate and a greater satisfaction in the “ true points ” groups ( P < 0.01 ) . Our results show that acupressure is an effective and simple-to-learn treatment of pain in emergency trauma care and leads to an improvement of the quality of care in emergency transport . We suggest that this technique is easy to learn and risk free and may improve paramedic-based rescue systems Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer 's disease ( AD ) , there is no convincing proof of a causal link for aluminium in disease progression . We have completed a two year , single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator , desferrioxamine . 48 patients with probable AD were r and omly assigned to receive desferrioxamine ( 125 mg intramuscularly twice daily , 5 days per week , for 24 months ) , oral placebo ( lecithin ) , or no treatment . No significant differences in baseline measures of intelligence , memory , or speech ability existed between groups . Activities of daily living were assessed and videorecorded at 6 , 12 , 18 , and 24 month intervals . There were no differences in the rate of deterioration of patients receiving either placebo or no treatment . Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means ( p = 0.03 ) and variances ( p less than 0.04 ) . The mean rate of decline was twice as rapid for the no-treatment group . Appetite ( n = 4 ) and weight ( n = 1 ) loss were the only reported side-effects . We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD BACKGROUND Elderly people often suffer from disturbed sleep . Because traditional Chinese medicine indicates that acupressure therapy may induce sedation , testing the effectiveness of acupressure in enhancing the quality of sleep of institutionalized residents with a well- design ed scientific study is needed . METHODS A r and omized block experimental design was used . The Pittsburgh Sleep Quality Index ( PSQI ) question naire was used as a screening tool to select subjects with sleep disturbance . By matching the effects of hypertension , hypnosis , naps , and exercise , subjects were r and omly assigned to an acupressure group , a sham acupressure group , and a control group . Each group had 28 subjects for a total of 84 subjects . The same massage routine was used in the acupressure group and the sham acupressure group , whereas only conversation was employed in the control group . RESULTS There were significant differences in PSQI subscale scores of the quality , latency , duration , efficiency , disturbances of sleep , and global PSQI scores among subjects in the three groups before and after interventions . Furthermore , there was a significant reduction in the frequencies of nocturnal awakening and night wakeful time in the acupressure group compared to the other two groups . CONCLUSIONS This study confirmed the effectiveness of acupressure in improving the quality of sleep of elderly people and offered a nonpharmacological therapy method for sleep-disturbed elderly people The objective of this study was to assess whether nicotine replacement therapy , administered in a real-life situation , could reduce cigarette consumption in smokers who were not prepared to quit smoking . Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and r and omly assigned to either a 6-month treatment of nicotine ( choice among a 15-mg nicotine patch , a 4-mg nicotine gum , a 10-mg nicotine inhaler , or a combination of these , N = 265 ) , matching placebo products ( N = 269 ) , or no intervention ( N = 389 ) . Products were sent to participants by mail . Education was limited to a booklet . Of 923 participants , 879 ( 95 % ) were followed up after 6 months . Mean baseline consumption was 30 cigarettes per day in all groups . At 6 months , cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group , 7.5 in the placebo group , and 2.5 among controls ( p < 0.04 for all pair-wise comparisons ) . Smoking cessation rates were low ( 2%–4 % ) and did not differ significantly between groups . Quit attempts were less frequent among controls ( 21 % ) than among the nicotine ( 28 % , p = 0.04 ) and placebo ( 27 % , p = 0.08 ) subjects . In conclusion , nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months , but a large part of this reduction was attributable to a placebo effect . Nicotine treatment for smoking reduction had no detectable impact on smoking cessation The influence of four variables ( status of communicator of drug effects , attitude of dentist , attitude of dental technician , and message of drug effects ) on the obtainment of placebo effects in an oral surgery clinic was investigated . Dependent variables were ( 1 ) rating of pain experienced from m and ibular-block injection , ( 2 ) pre-post placebo state anxiety , and ( 3 ) pre-postplacebo fear of injection . Enthusiastic messages of drug effects produced statistically and clinical ly significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic . Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive , only the attitude factors obtained statistical significance . The status of the communicator accounted for very small portions of the variance A study was design ed to document and quantify the changes in lens clarity over 6 and 24 months in 2 groups of 49 volunteers ( 76 eyes ) with an average age of 65.3 + /- 7.0 enrolled at the time of diagnosis of senile cataracts of minimal to advanced opacification . The patients received N-acetylcarnosine , 1 % sol ( NAC ) ( 26 patients , 41 eyes = Group II ) , placebo composition ( 13 patients , 21 eyes ) topically ( two drops , twice daily ) to the conjunctival sac , or were untreated ( 10 patients , 14 eyes ) ; the placebo and untreated groups were combined into the control ( reference ) Group I. Patients were evaluated upon entry , at 2-month ( Trial 1 ) and 6-month ( Trial 2)-intervals for best corrected visual acuity ( b/c VA ) , by ophthalmoscopy and the original techniques of glare test ( for Trial 1 ) , stereocinematographic slit-image and retro-illumination photography with subsequent scanning of the lens . The computerized interactive digital analysis of obtained images displayed the light scattering/absorbing centers of the lens into 2-D and 3-D scales . The intra-reader reproducibility of measuring techniques for cataractous changes was good , with the overall average of correlation coefficients for the image analytical data 0.830 and the glare test readings 0.998 . Compared with the baseline examination , over 6 months 41.5 % of the eyes treated with NAC presented a significant improvement of the gross transmissivity degree of lenses computed from the images , 90.0 % of the eyes showed a gradual improvement in b/c VA to 7 - 100 % and 88.9 % of the eyes ranged a 27 - 100 % improvement in glare sensitivity . Topographic studies demonstrated less density and corresponding areas of opacification in posterior subcapsular and cortical morphological regions of the lens consistent with VA up to 0.3 . The total study period over 24 months revealed that the beneficial effect of NAC is sustainable . No cases result ed in a worsening of VA and image analytical readings of lenses in the NAC-treated group of patients . In most of the patients drug tolerance was good . Group I of patients demonstrated the variability in the densitometric readings of the lens cloudings , negative advance in glare sensitivity over 6 months and gradual deterioration of VA and gross transmissivity of lenses over 24 months compared with the baseline and 6-month follow-up examinations . Statistical analysis revealed the significant differences over 6 and 24 months in cumulative positive changes of overall characteristics of cataracts in the NAC-treated Group II from the control Group I. The N-acetylated form of natural dipeptide L-carnosine appears to be suitable and physiologically acceptable for nonsurgical treatment for senile cataracts & NA ; Response expectancies have been proposed as the major determinant of placebo effects . Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice . Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days , together with a basal intravenous infusion of saline solution . However , the symbolic meaning of this basal infusion was changed in three different groups of patients . The first group was told nothing about any analgesic effect ( natural history ) . The second group was told that the basal infusion was either a powerful painkiller or a placebo ( classic double‐blind administration ) . The third group was told that the basal infusion was a potent painkiller ( deceptive administration ) . Therefore , whereas the analgesic treatment was exactly the same in the three groups , the verbal instructions about the basal infusion differed . The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three‐days treatment . We found that the double‐blind group showed a reduction of buprenorphine requests compared to the natural history group . However , this reduction was even larger in the deceptive administration group . Overall , after 3 days of placebo infusion , the first group received 11.55 mg of buprenorphine , the second group 9.15 mg , and the third group 7.65 mg . Despite these dose differences , analgesia was the same in the three groups . These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects , which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake In a multicenter r and omized controlled trial involving 220 women with retained placenta no beneficial effects could be established of intraumbilical vein administration of 10 IU of oxytocin in 20 ml of saline solution . A reduction was not gained in the rate of manual removal of the placenta and there was no decrease in the amount of blood loss . Oxytocin only induced a minor shortening of the median time interval from administration to the spontaneous expulsion of the placenta as compared with a placebo injection . Maternal serum alpha-fetoprotein levels before and after intraumbilical vein injection did not show evidence of fetomaternal transfusion Patients usually fear fiberoptic bronchoscopy ( FBS ) and they report a low level of satisfaction after this examination . We evaluated the efficacy of acupuncture in decreasing patient anxiety before diagnostic FBS and in improving tolerance to the examination . In a prospect i ve double-blind study , we enrolled 48 patients scheduled to undergo diagnostic FBS . Patients were r and omly assigned to one of three groups . Group A ( 16 patients ): st and ard FBS , with airway topic anesthesia ; Group B ( 16 patients ): st and ard FBS , with airway topic anesthesia and acupuncture treatment ; Group C ( 16 patients ): st and ard FBS , with airway topic anesthesia and sham acupuncture . EKG , non-invasive arterial pressure , and pulse oximetry were monitored on a routine basis . We evaluated patient anxiety before and after acupuncture and , at the end of FBS , the discomfort suffered during the examination by a 100-mm Visual Analog Scale ( VAS ) . Patient satisfaction in Group A was 50 % worse than in Group B ( p = 0.04 ) . We observed a strong , even if not statistically significant , tendency toward a lower pre-FBS anxiety in Group B. Patients in group C had values very close to those recorded in group A. We observed no adverse event and no differences in cardio-respiratory parameters in these three groups ; in particular , we did not observe a respiratory depression in Group B. Acupuncture seems an effective re source for a Thoracic Endoscopic Room to improve patient tolerance to FBS BACKGROUND / AIMS Gastroscopic procedure causes nausea and retching in many patients . Recently , alternative methods have been employed in an effort to reduce these symptoms . The Neiguan point ( P6 ) is an acupuncture point that has been used for approximately 3,000 years to overcome gastric symptoms including nausea and retching . The aim of this study was to investigate the effects of the stimulation of the P6 acupoint on swallowing , nausea and retching during the gastroscopic procedure . METHODS Three hundred and twenty-seven patients who visited the gastroenterology unit for dyspeptic complaints were included in the study . A portable transcutaneous electrical nerve stimulation device ( Reliefb and ; Maven Lab , Yuba City , CA ) was used for acustimulation . The device was attached 15 minutes before the endoscopic procedure and no sedation was applied . The device was turned on in 78 patients ( Group 1 ) . The device was attached but not turned on in another 79 patients ( Group 2 ) . In Group 3 , the device was attached to the Sham point ( n : 79 ) . In Group 4 the procedure was performed with no attachments ( n : 77 ) . Fourteen patients dropped out of the study because esophagogastroduodenoscopy could not be completed due to patient intolerance or to obstruction in the upper gastrointestinal tract . After the procedure , each patient 's opinion about the severity of nausea and retching was measured on a visual analogue scale . Distress in swallowing and the impression of the endoscopist during the procedure were scored from 1 to 4 . Patients were queried regarding their willingness to undergo re-endoscopy . RESULTS Groups were compared regarding their distress in swallowing the endoscope , nausea and retching , the impression of the endoscopist during the procedure and their acceptance of re-endoscopy . Groups 1 , 2 , 3 and 4 were compared using the chi-square test , and no significant difference was observed between the groups ( p>0.05 ) . CONCLUSIONS Acustimulation of the Neiguan ( P6 ) acupoint does not relieve patients of the nausea observed during gastroscopy , and its application does not facilitate the procedure Objective : To determine the safety of a vaginal microbicide , COL-1492 , containing 52.5 mg nonoxynol-9 , applied once daily for 14 days among healthy volunteers . Methods : A r and omized , double-blind controlled trial with three arms , COL-1492 gel versus placebo gel versus no-treatment controls , was conducted . Outcomes of interest were reported genital symptoms , incidence of gynaecological signs , and incidence of genital lesions revealed by colposcopy . Participants were enrolled in four centres ( Belgium , The Netherl and s , and two in Thail and ) . Results : A total of 534 women participated in the study : 179 used COL-1492 , 178 used placebo , and 177 were no-treatment controls . Study visits were scheduled 1 week prior to enrolment ( day −7 ) , day 0 ( enrolment ) , day 8 and day 14 . The most frequently reported genital symptom was vaginal discharge in both the COL-1492 and placebo groups . This appeared to be related to leakage of the product out of the vagina . The incidence of lesions associated with epithelial disruption ( ulcers and abrasions ) was very low ( < 2 % ) and there was no statistically significant difference between the three groups . Of the lesions observed by colposcopy that did not involve epithelial disruption , petechial haemorrhage was the most frequently detected , with an incidence of 20.1 , 9.0 and 7.3 % in the COL-1492 , placebo and control groups , respectively . COL-1492 users had a higher incidence of erythema ( 8.4 versus 2 % in the other groups ) . Conclusion : COL-1492 showed minimal toxicity when applied once daily . A Phase III trial to assess the product 's effectiveness in HIV prevention is currently ongoing The purpose of the study was to determine the effect of ethyl vinyl chloride vapocoolant spray on pain reported by children undergoing intravenous cannulation . A r and omized , double-blinded , placebo-controlled trial was conducted on eligible children between the ages of 9 and 18 years seen in a pediatric emergency department and requiring intravenous cannulation . Informed consent was obtained , and children were r and omized to receive ethyl vinyl chloride spray , isopropyl alcohol spray , or no spray ( control group ) . Patient demographics and information pertaining to each intravenous cannulation were recorded . Children indicated the degree of pain associated with intravenous cannulation on a 100-mm visual analog scale ( VAS ) compared to a baseline pain score of “ zero . ” Statistical analysis was performed by using Stata version 7 . One hundred twenty-seven subjects were enrolled : 37 received ethyl vinyl chloride vapocoolant spray , 48 received isopropyl alcohol spray ( placebo ) , and 42 received no pretreatment . Mean VAS scores for pain experienced during cannulation were 34 , 33 , and 31 mL for each group , respectively . Ethyl vinyl chloride vapocoolant spray failed to measurably reduce pain associated with intravenous cannulation when compared to those pretreated with isopropyl alcohol spray or receiving no intervention We report clinical data on the efficacy of acupuncture for alcohol dependence . 503 patients whose primary substance of abuse was alcohol participated in this r and omized , single blind , placebo controlled trial . Patients were assigned to either specific acupuncture , nonspecific acupuncture , symptom based acupuncture or convention treatment alone . Alcohol use was assessed , along with depression , anxiety , functional status , and preference for therapy . This article will focus on results pertaining to alcohol use . Significant improvement was shown on nearly all measures . There were few differences associated with treatment assignment and there were no treatment differences on alcohol use measures , although 49 % of subjects reported acupuncture reduced their desire for alcohol . The placebo and preference for treatment measures did not material ly effect the results . Generally , acupuncture was not found to make a significant contribution over and above that achieved by conventional treatment alone in reduction of alcohol use BACKGROUND Frequent blood glucose ( BG ) monitoring is a critical component of diabetes management , yet many barriers exist to consistent monitoring . METHODS In this r and omized controlled trial , we sought to determine if an educational manual , the Blood Sugar Monitoring Owner 's Manual ( BGMOM ) , could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results . The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes ( hemoglobin A(1C ) > or=8.0 % ) ; 35 % had type 1 diabetes mellitus . Participants were r and omized to 1 of 3 groups : BGMOM intervention ( BGM+ ) , attention control ( BG meter only [ MT ] ) , or st and ard care ( SC ) . The BGM+ and MT groups received BG meters and meter education ; the BGM+ group also received BGMOM booklets . The SC group received usual care . Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C ) measurement . RESULTS Monitoring frequency increased significantly in the BGM+ group ( 1.9 + /- 1.3 to 2.8 + /- 1.5 times daily , P<.001 ) but only slightly in the MT group ( 1.7 + /- 1.3 to 2.0 + /- 1.3 times daily ) . The BGM+ group experienced the greatest improvement in hemoglobin A(1C ) level ( BGM+ : -0.13 + /- 1.28 ; MT : -0.04 + /- 1.31 ; SC : 0.04 + /- 1.10 ) . Further , a higher percentage of those in the BGM+ group ( 61 % ) improved their glycemic control compared with the other groups ( 44 % ; P = .05 ) . Finally , the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C ) ( P = .04 ) and reported the least amount of negative affect about out-of-range BG monitoring results ( P = .03 ) . CONCLUSION As an adjunct to st and ard diabetes education and support , a manual such as the BGMOM can help optimize BG monitoring and glycemic control OBJECTIVE To assess the effectiveness of sucrose as an analgesic agent during routine immunization injections for infants ( age range , 2 weeks to 18 months ) . STUDY DESIGN Double-blind , r and omized control trial . SETTING Ambulatory care clinic of a large tertiary care center . PARTICIPANTS A consecutive sample of 285 infants were r and omly assigned to one of three treatment groups . INTERVENTION Subjects received either no intervention or drank 2 mL of sterile water or 2 mL or a 12 % sucrose solution 2 minutes before administration of the immunization . MAIN OUTCOME MEASURE Infants were videotaped during immunization for later interval recording of pain-induced vocalizations . RESULTS Results were analyzed by using two-way repeated measure analyses of variance . Two-week-old infants who received either the sterile water or sucrose solution cried significantly less than infants who received no intervention ( F=5.92,P<.005 ) . For older infants , those who received water or sucrose cried significantly less only if they were administered one injection rather than two injections ( F=3.36,P<.05 ) . CONCLUSIONS We found that when infants drank sucrose or sterile water , significantly fewer pain vocalizations were produced , but only for 2-week-old infants . For older infants , differences were found only when the number of injections was included in the analysis . We exp and on previous findings by demonstrating that both the age of the child and the number of painful exposures can attenuate calming effects . In addition , the results suggest that in the absence of nonnutritive sucking , the actual analgesic effects of sucrose may be nonspecific . Further study is needed of the possible analgesic effects of sucrose OBJECTIVE To evaluate the effect of vaginal disinfection with chlorhexidine gel during labor on vertical transmission of group B streptococcus , as a method to prevent vertical transmission and subsequent neonatal early onset group B streptococcal disease . STUDY DESIGN A prospect i ve study with r and omization of 1020 parturients to one of three groups as soon as labor started . In all parturients , anus , introitus and cervix were cultured semiquantitatively . Two groups were treated double-blindly with 10 ml of either a 0.3 % chlorhexidine gel or a placebo gel , applicated around the portio and into the fornices . If labor still continued , a second application was given after 10 h. The third group received no treatment . Ear , pharynx and umbilicus of all newborns were also cultured semiquantitatively . RESULTS Nine hundred and eighty one women were evaluated . The overall incidence of group B streptococcal carriership was 19.4 % . Vertical transmission was 52.4 % in the chlorhexidine group , 71.4 % in the placebo group and 66.7 % in the control group ( P = 0.069 ) . When testing the transmission rates for the chlorhexidine versus the combined placebo plus control group ( 69.3 % ) , the difference was 16.9 % ( P = 0.026 ) . CONCLUSION Vaginal disinfection with a chlorhexidine gel during labor modestly reduces group B streptococcal vertical transmission . Because the method is cheap , simple and safe , it should be considered for routine use . Our results indicate that it may reduce the incidence of early onset group B streptococcal sepsis by 2 - 32 % Women with orgasmic difficulties are commonly taught pubococcygeal ( PC ) muscle exercises which , practice d regularly , are said to have both specific and nonspecific beneficial effects on sexual enjoyment . The hypothesis tested was that women practicing these exercises over a 12-week period , would be more likely to become orgasmic than women practicing relaxation exercises , or than women in an attention-control group . Forty-six women were allocated to one of three groups , PC exercise , relaxation or control . PC muscle tone was measured and question naires about sexual response were completed over a 12-week period with a 6-month follow-up assessment . Results indicated that there was no difference in orgasmic outcome for the three groups during the experimental period . This was taken to imply that PC exercises are not of specific value for women with normal muscle tone . It remains possible that women with poor muscle tone are helped by the exercises and further research is considered necessary in this area OBJECTIVE This r and omized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia ( FM ) syndrome . We hypothesized that the combination of group education with cognitive treatment aim ed at developing pain coping skills would be more effective than group education alone . METHODS 131 patients with FM were r and omly assigned to 3 conditions : an experimental condition , which was the combined cognitive/educational intervention ( ECO ) ; an attention control condition consisting of group education plus group discussion ( EDI ) ; and a waiting list control ( WLC ) . For the treatment conditions ECO and EDI , assessment s were made 2 weeks before treatment , at start of treatment , at post-treatment , and at 6 and 12 mo followup . WLC patients received only 3 assessment s. RESULTS There were no pretreatment differences between the groups , or between dropouts and patients who remained in the study . At post-treatment , and compared with the WLC , the ECO patients improved in knowledge about FM ( p = 0.007 ) and pain coping ( p < 0.001 ) . EDI patients improved on pain coping ( p = 0.005 ) and pain control ( p = 0.002 ) . EDI patients reported significantly less fear than ECO patients ( p = 0.005 ) . There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup . Based on the reliability of change index for clinical significance , the relative short term success rates are 6.4 and 18.4 % for ECO and EDI , respectively . CONCLUSION The surplus value of a highly structured , 12 session group cognitive treatment added to group education can not be supported by our study . In EDI , fear reduction might have enhanced pain coping and pain control , while poor compliance , the difficulty of homework assignments , and lack of individual support may have limited the effectiveness of ECO OBJECTIVE : To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements . METHOD : Thirty-four essential hypertensive out patients were r and omly allocated after a 4-week pre selection period in two groups in a cross-over study design . One group received placebo for 4 weeks while the other formed the control group ( reproducibility ) , then the treatments were exchanged for another 4 weeks . Clinic and ambulatory blood pressures were measured at three different times for each patient , namely bnefore the r and om allocation to groups and at the end of each period , using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring . RESULTS : Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures ( by 3.4+/-13 and 3.6+/-8 mmHg , respectively ) , but not in 24 h , daytime and night-time blood pressures . Circadian hourly blood pressure and heart rate curves were virtually superimposable . In the 13 placebo responder patients selected on the basis of clinic blood pressure , placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures , mainly during the day period ( by 5.2+/-6.2 and 4.89+/-7.8 mmHg , respectively ) . This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference . To characterize at baseline the placebo responder patients , comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group . CONCLUSION : The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo ( placebo responders ) ; the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis . This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs The childhood diarrhoea-management guidelines of the World Health Organization/United Nations Children 's Fund ( WHO/UNICEF ) now include zinc treatment , 20 mg per day for 10 days . To determine if a dispersible zinc sulphate tablet formulation is associated with increased risk of vomiting or regurgitation following the initial , first treatment dose , a double-blind , placebo-controlled r and omized clinical trial was carried out in the Dhaka hospital of ICDDR , B : Centre for Health and Population Research ( n=800 ) and in an adjacent NGO outpatient clinic ( n=800 ) . Children were r and omized to one of three groups : no treatment , placebo , or zinc sulphate tablet ( 20 mg ) . They were then observed for 60 minutes , and all vomiting or regurgitation episodes were recorded . When compared with placebo , zinc treatment result ed in an attributable risk increase of 14 % for vomiting and 5.2 % for regurgitation . The median time to vomiting among those receiving zinc was 9.6 minutes and was limited to one episode in 91.2 % of the cases . Overall , the proportion of 60-minute post-treatment vomiting attributable to zinc , placebo , and the illness episode was estimated to be 40 % , 26 % , and 34 % respectively . The dispersible zinc sulphate tablet formulation at a dose of 20 mg is associated with increased risks of vomiting and regurgitation . Both are transient side-effects The present study evaluated the efficacy of group cognitive-behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients . Twenty-seven out patients were r and omly assigned to one of three groups : Cognitive-Behavior Therapy , Supportive Counseling ( attention-placebo control ) , and Waiting list ( no treatment control ) . The major outcome measures used were : patient 's , neurologist 's , and therapist 's global ratings of psychological adjustment , patient 's target complaints and weekly seizure frequency , patient 's and neurologist 's ratings of seizure control , the Minnesota Multiphasic Personality Inventory , the Washington Psychosocial Seizure Inventory , and the Beck Depression Inventory . No significant differences were found among the three groups on these measures except for therapist 's global ratings of psychological adjustment , on which both the Cognitive-Behavior Therapy and Supportive Counseling groups improved significantly after therapy , but the Waiting List control group did not . Overall , little support was found for the efficacy of group cognitive behavior therapy ( eight 2-h weekly sessions ) for the reduction of psychosocial difficulties or seizures . Implication s of the present findings are discussed , with the need for further controlled outcome research stressed OBJECTIVE To design and evaluate an office-based intervention aim ed at maintaining parent-adolescent teamwork in diabetes management tasks without increasing diabetes-related family conflict . RESEARCH DESIGN AND METHODS There were 85 patients ( aged 10 - 15 years , mean 12.6 years ) with type 1 diabetes ( mean duration 5.5 years ; mean HbA1c 8.5 % ) who were r and omly assigned to one of three study groups -- teamwork , attention control , and st and ard care-- and followed for 24 months . At each visit , parent involvement in insulin administration and blood glucose monitoring was assessed . The teamwork and attention control interventions were integrated into routine ambulatory visits over the first 12 months ( four medical visits ) . Measures of diabetes-related family conflict were collected at baseline and after 12 months . All patients were followed for an additional 12 months with respect to glycemic control . RESULTS In the teamwork group , there was no major deterioration ( 0 % ) in parent involvement in insulin administration , in contrast to 16 % major deterioration in the combined comparison ( attention control and st and ard care ) group ( P < 0.03 ) . Similarly , no teamwork families showed major deterioration in parent involvement with blood glucose monitoring versus 11 % in the comparison group ( P < 0.07 ) . On both the Diabetes Family Conflict Scale and the Diabetes Family Behavior Checklist , teamwork families reported significantly less conflict at 12 months . An analysis of HbA1c over the 12- to 24-month follow-up period indicated that more adolescents in the teamwork group ( 68 % ) than in the comparison group ( 47 % ) improved their HbA1c ( P < 0.07 ) . CONCLUSIONS The data demonstrate that parent involvement in diabetes management tasks can be strengthened through a low-intensity intervention integrated into routine follow-up diabetes care . Moreover , despite increased engagement between teen and parent centered around diabetes tasks , the teamwork families showed decreased diabetes-related family conflict . Within the context of a broader cultural recognition of the protective function of parent involvement in the lives of adolescents , the findings of this study reinforce the potential value of a parent-adolescent partnership in managing chronic disease & NA ; The effect of treatment with ultrasound , massage and exercises on myofascial trigger‐points ( MTrP ) in the neck and shoulder was assessed in a r and omised controlled trial . The outcome measures were pain at rest and on daily function ( Visual Analogue Scale , VAS ) , analgesic usage , global preference and index of MTrP. Long‐term effect for treatment and control groups was assessed after 6 months using a question naire . The patients were r and omised to three groups . The first group was treated with ultrasound , massage and exercise ( A ) , the second group with sham‐ultrasound , massage and exercise ( B ) , while the third group was a control group ( C ) . The duration of the study was 6 weeks . Treatment was given twice a week from the second to the fifth week . The number and index of MTrPs were recorded at each treatment session in groups A and B but only at entry as well as end of study in group C. VAS and analgesic usage was recorded in all three groups throughout the study period . Six months after the last treatment session a question naire was send to the patients . A total of 67 patients were included . Nine patients dropped‐out during the study , which left 58 patients that could be included in the final analysis . Twenty patients were r and omised to group A , 18 to group B and 18 to group C. A significant reduction in index were found between treatment groups ( A and B ) and control group ( C ) , but no difference between group A and B. VAS scores , analgesic usage or global preference showed no difference between group A , B or C. The patients in the group C were offered treatment ( ultrasound , massage , exercise ) after the 6 weeks treatment period . At the question naire after 6 month 44 ( 87 % ) of the 52 patients from all three groups who had treatment responded . Sixty‐four percent answered that they had had good or some effects , 68 percent were still doing the exercise programme and 17 percent had received other forms of therapy after they had completed the study . No difference between groups given ultrasound or sham ultrasound were found . It is concluded that US give no pain reduction , but apparently massage and exercise reduces the number and intensity of MTrP. The impact of this reduction on neck and shoulder pain is weak Pharmacologic studies in hypertension often describe blood pressure ( BP ) reductions in placebo control groups . This placebo effect is currently debated , as it seems to be related to BP measurement methods and as a regression to the mean phenomenon may lead to misinterpretation . Furthermore , data on pulse pressure are lacking . This study was design ed to evaluate the placebo effect on BP and to differentiate it from regression to the mean . According to a crossover design , 26 mild-to-moderate hypertensive patients who were treated with placebo or given no treatment were followed-up for 1 month . Clinic and ambulatory BP was assessed at baseline and at the end of each 1-month period . Placebo administration result ed in significant reductions in clinic systolic , diastolic , and mean BP ( P < .01 ) , ambulatory 24-h SBP ( P < .05 ) , and daytime systolic , diastolic , and mean BP ( P < .01 , P < .05 , P < .01 , respectively ) . No significant differences were noted for pulse pressure and heart rate or between BP values measured at baseline and after 1 month without treatment . Despite a significant correlation between changes in clinic and ambulatory BP , the scatter of individual data suggests that the placebo response observed with one method can not be systematic ally extrapolated to the other method . This study conclusively shows the effect of placebo in mild-to-moderate hypertension on both clinic and ambulatory systolic , diastolic , and mean BP , in which it has been shown to differ from the regression to the mean phenomenon . This effect was not observed for pulse pressure or heart rate CONTEXT Substantial evidence suggests that acupuncture-point stimulation may be effective in controlling side effects of chemotherapy . OBJECTIVE To examine the efficacy of an acustimulation wristb and for the relief of chemotherapy-induced nausea . DESIGN R and omized clinical trial using a 3-level crossover design . SETTING Three outpatient oncology clinics in the northeastern United States . PARTICIPANTS Twenty-five women and 2 men who experienced moderate or more severe nausea following their first chemotherapy treatment . INTERVENTION We compared active acustimulation of the Pericardium 6 ( PC-6 ) point on the ventral surface of the wrist with sham acustimulation ( a corresponding point on the posterior surface of the wrist ) . A control group received no acustimulation . OUTCOME MEASURES Severity of nausea and quantity of antiemetic medication used . RESULTS No statistically significant differences in average severity of nausea were observed between the 3 interventions . However , the data showed a difference close to statistical significance in the severity of delayed nausea reported during active acustimulation compared to no acustimulation ( P < .06 ) . In addition , patients took fewer antinausea pills during the active-acustimulation cycle of this experiment compared to the no-acustimulation phase ( P < .05 ) . CONCLUSION Findings on the efficacy of an acustimulation b and for the control of chemotherapy-induced nausea are positive but not conclusive . These findings provide ample justification for further study of acustimulation in clinical oncology Purpose To investigate the effect of sensory stimulation of the P6 point on postoperative nausea and vomiting ( PONV ) after gynecological surgery in the everyday clinical setting ( effectiveness study ) . Methods Four hundred and ten women undergoing general anesthesia for elective gynecological surgery were included in a prospect i ve , consecutive , r and omized , multicentre , placebo-controlled , double-blind clinical trial with a reference group . One group was given bilateral P6 acupressure ( n = 135 ) , a second group similar pressure on bilateral non-acupressure points ( n = 139 ) , and a third group ( n = 136 ) served as reference group . Nausea ( scale 0–6 ) , vomiting , pain , and satisfaction with the treatment were recorded . Primary outcome was complete response , i.e. , no nausea , vomiting or rescue medication for 24 hr . Results were analyzed by applying logistic regression with indicators of treatments , type of operation and risk score for PONV as explanatory variables . Results Complete response was more frequent in the P6 acupressure group than in the reference group ( P = 0.0194 ) Conversely , the incidence of PONV was 46 % in the reference group , 38 % after pressure on a non-acupoint and 33 % after P6 acupressure . The decrease from 46 % to 33 % was statistically significant . When considering vaginal cases separately , the decrease in PONV was from 36 % to 20 % ( P = 0.0168 ) . The corresponding decrease from 59 % to 55 % in the laparoscopic surgery group was not statistically significant . Conclusion P6 acupressure is a non-invasive method that may have a place as prophylactic antiemetic therapy during gynecological surgery . RésuméObjectifRechercher l’effet d’une stimulation sensorielle acupressive en P6 sur les nausées et vomissements postopératoires ( NVPO ) à la suite d’une intervention chirurgicale gynécologique dans un cadre clinique normal ( étude d’efficacité).MéthodeUn essai clinique prospect if , r and omisé , multicentrique , en double aveugle contre placebo et comportant un groupe de référence a été réalisé auprès de 410 femmes qui se sont présentées successivement pour une intervention gynécologique non urgente sous anesthésie générale . Les patientes d’un premier groupe ont reçu de l’acupression en P6 ( n = 135 ) , celles d’un second groupe ont reçu une pression semblable sur des points bilatéraux , non d’acupression , ( n = 139 ) et un troisième groupe ( n = 136 ) a servi de référence . Les nausées ( échelle de 0–6 ) , les vomissements , la douleur et la satisfaction face au traitement ont été notés . Le premier résultat était une réponse complète , donc absence de nausées , de vomissements ou de médication de secours pendant 24 h. Les résultats ont été analysés par régression logistique avec des indicateurs de traitements , le type d’intervention et le taux de risque de NVPO comme variables explicatives . RésultatsLa réponse complète a été plus fréquente avec l’acupression en P6 que chez les patientes témoins ( P = 0,0194 ) . Inversement , l’incidence de NVPO a été de 46 % dans le groupe de référence , 38 % après une pression de points non acupresseurs et 33 % après l’acupression en P6 . La diminution de 46 % à 33 % était significative . L’examen séparé des cas d’intervention vaginale indique une baisse des NVPO de 36 % à 20 % ( P = 0,0168 ) . La baisse correspondante de 59 % à 55 % dans les cas d’intervention laparoscopique n’était pas significative . Conclusion L’acupression en P6 représente une méthode non effractive de traitement antiémétique prophylactique qui peut avoir sa place pendant une intervention gynécologique Background Disruptive behaviors are prevalent in nursing home residents with dementia and often have negative consequences for the resident , caregiver , and others in the environment . Behavioral interventions might ameliorate them and have a positive effect on residents ’ mood ( affect ) . Objectives This study tested two interventions —an activities of daily living and a psychosocial activity intervention— and a combination of the two to determine their efficacy in reducing disruptive behaviors and improving affect in nursing home residents with dementia . Methods The study had three treatment groups ( activities of daily living , psychosocial activity , and a combination ) and two control groups ( placebo and no intervention ) . Nursing assistants hired specifically for this study enacted the interventions under the direction of a master ’s prepared gerontological clinical nurse specialist . Nursing assistants employed at the nursing homes recorded the occurrence of disruptive behaviors . Raters analyzed videotapes filmed during the study to determine the interventions ’ influence on affect . Results Findings indicated significantly more positive affect but not reduced disruptive behaviors in treatment groups compared to control groups . Conclusions The treatments did not specifically address the factors that may have been triggering disruptive behaviors . Interventions much more precisely design ed than those employed in this study require development to quell disruptive behaviors . Nontargeted interventions might increase positive affect . Treatments that produce even a brief improvement in affect indicate improved quality of mental health as m and ated by federal law The local analgesic efficacy of a cream formulation of lidocaine and prilocaine ( EMLA ® ) in reducing pain at venous cannulation was investigated in children scheduled for elective surgery . Forty children participated in a double‐blind , r and omized comparison between EMLA and inactive placebo cream . Another group of 18 children without any local treatment was studied as an additional control material . Subjective pain scores , expressed with a visual analogue scale , were significantly lower in the EMLA group compared with both the group treated with placebo cream ( P<0.001 ) and the open control group ( no cream ; P<0.01 ) . Local pallor and slight oedema were the only side‐effects , registered in both cream‐treated groups . A preliminary study was also carried out with 10 children ( five with EMLA and five without ) in order to determine whether catecholamine and vasopressin levels in venous blood are affected by the stress and anxiety associated with venepuncture in children premedicated with oral flunitrazepam . No significant hormone responses were , however , detected . The lidocaine concentrations measured in venous blood taken from the application site of EMLA cream were low , and there were no measurable levels of lidocaine in simultaneous blood sample s from the opposite extremity . In our opinion EMLA cream is safe and alleviates effectively the pain associated with venepuncture , and thus deserves a place in the routine premedication of children OBJECTIVE Our aim was to find out whether intravenous fentanyl was effective in reducing the pain of first-trimester abortion . STUDY DESIGN This r and omized controlled trial included 825 women attending a nonhospital abortion facility . Some women chose st and ard care . Women who did not choose st and ard care were r and omly assigned to receive either 50 to 100 microg of fentanyl , a placebo , or no intervention . With SAS software and a mixed effects analysis of variance model with covariates , we compared mean pain scores of the fentanyl and placebo groups to detect a difference of at least 1 point on an 11-point pain scale . RESULTS The mean pain score of the fentanyl group was 1.0 point less than that of the placebo group ( 95 % confidence interval , 3.7 - 4.3 ) and 0.9 point less than that of the observational group ( 95 % confidence interval , 4.7 - 5.1 ) . This pain reduction was statistically significant , but the women who were studied wanted a 2-point reduction from fentanyl . CONCLUSION Fentanyl , when compared with the placebo , reduced abortion pain by 1.0 point on an 11-point scale . This reduction was of question able clinical significance and was less than desired by the women included in the study OBJECTIVE To compare the antiemetic effect of acupressure at the Neiguan point ( P6 ) in a group of healthy women with normal pregnancy and nausea and vomiting during pregnancy ( NVP ) with a similar group receiving acupressure at a placebo point and another , similar group not receiving any treatment . STUDY DESIGN A r and omized , placebo-controlled , pilot study involving 60 women . RESULTS It is possible to reduce NVP significantly with acupressure at P6 as compared to acupressure at a placebo point or no treatment at all in healthy women with normal pregnancies . Relief from nausea appeared one day after starting treatment in both the P6 and placebo groups but lasted for only six days in the placebo group . The P6 group , however , experienced significantly less nausea after 14 days as compared to the other two groups . CONCLUSION This study involved 60 healthy women with normal pregnancy and suffering from NVP . According to the results , in healthy women with normal pregnancy it is possible to reduce NVP significantly at P6 as compared to acupressure at a placebo point and to no treatment BACKGROUND Conventional dentoalveolar osseous reconstruction often involves the use of grafting material s with or without barrier membranes . The purpose of this study was to evaluate the efficacy of bone induction for the placement of dental implants by two concentrations of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) delivered on a bioabsorbable collagen sponge ( ACS ) compared to placebo ( ACS alone ) and no treatment in a human buccal wall defect model following tooth extraction . METHODS Eighty patients requiring local alveolar ridge augmentation for buccal wall defects ( > or = 50 % buccal bone loss of the extraction socket ) of the maxillary teeth ( bicuspids forward ) immediately following tooth extraction were enrolled . Two sequential cohorts of 40 patients each were r and omized in a double-masked manner to receive 0.75 mg/ml or 1.50 mg/ml rhBMP-2/ACS , placebo ( ACS alone ) , or no treatment in a 2:1:1 ratio . Efficacy was assessed by evaluating the amount of bone induction , the adequacy of the alveolar bone volume to support an endosseous dental implant , and the need for a secondary augmentation . RESULTS Assessment of the alveolar bone indicated that patients treated with 1.50 mg/ml rhBMP-2/ACS had significantly greater bone augmentation compared to controls ( P < or = 0.05 ) . The adequacy of bone for the placement of a dental implant was approximately twice as great in the rhBMP-2/ACS groups compared to no treatment or placebo . In addition , bone density and histology revealed no differences between newly induced and native bone . CONCLUSION The data from this r and omized , masked , placebo-controlled multicenter clinical study demonstrated that the novel combination of rhBMP-2 and a commonly utilized collagen sponge had a striking effect on de novo osseous formation for the placement of dental implants This study evaluated the effectiveness of a videotaped behavioral treatment program in reducing dental anxiety in emergency oral surgery patients . It compared a videotaped placebo program and a no-treatment control condition . Anxiety , measured for two periods during the study ( an anticipatory phase just before oral surgery and a post oral surgery phase ) , was evaluated by means of self-report , physiological , and behavioral observation measures . Results revealed significant treatment group as well as Group X Sex interaction effects for the heart rate index of physiological arousal . Results also revealed that the treatment program was reported by subjects to be significantly more helpful than the placebo program . Overall , these results suggest that a short , videotaped behavioral intervention can have a positive effect on the oral surgery patient , and that the sex of the subject may be an important variable to be incorporated in evaluating the effectiveness of this type of treatment program We analyzed the efficacy of a single daily dose of labetalol ( 300 mg ) administered at 9 a.m. in six in patients suffering from medium-severe hypertension . The study was conducted on 3 consecutive days , during which the patients were on labetalol , placebo , and non-treatment ( control ) according to a trial design of the Latin square type , balanced for residual effects . The hypotensive effect of labetalol manifests itself between hours 1 and 2 after administration of the drug . The systolic and diastolic blood pressure values always proved lower after labetalol as compared to placebo and non-treatment ( control ) as well as to the average of the latter two values ( placebo + control ) divided by 2 . No side effects were detected We undertook a r and omized , double-blind , placebo-controlled study to investigate the therapeutic effect of vitamin B6 on carpal tunnel syndrome . After ten weeks in the study , ten of 15 patients improved ( this included patients given placebo and those given no treatment ) . Vitamin B6 seems to have no advantage over conservative therapy for carpal tunnel syndrome . This study also suggests that repeat electrodiagnostic testing is no more useful than clinical symptoms in deciding on surgical intervention after unsuccessful conservative therapy OBJECTIVE To evaluate the use of oral iron replacement therapy as an effective treatment for acute surgically induced anemia . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Perioperative acute care hospital and a surgery clinic for a single cardiothoracic physician group . PATIENTS One hundred twenty-eight men and postmenopausal women , 50 years of age or older , admitted for elective coronary artery bypass surgery over a consecutive 8-month period . OUTCOME MEASURES Before surgery : serum iron , serum ferritin , hemoglobin and hematocrit . Six days after surgery : hemoglobin and hematocrit . Mean of 59 days after surgery : serum iron , serum ferritin , hemoglobin and hematocrit . INTERVENTION Patients were r and omized to one of four groups : control group ; placebo group ; low-dose group , 50 mg elemental iron + 60 mg ascorbic acid in a multi-vitamin daily ; and usual-dose group , 200 mg elemental iron daily . RESULTS One hundred twenty-one subjects completed the study : 100 men ( 82.6 % ) mean age 64.5 years and 21 women ( 17.4 % ) , mean age 65.7 years . There were no statistically significant age or gender differences among groups . Statistical analysis revealed , except for side effects , no differences between or among groups for any variable measured during the last two time intervals . The mean hemoglobin and hematocrit of the entire sample at 6 days was 9.5 + /- 1.2 gm/dl and 28 % + /- 2.3 % , respectively . At a mean of 59 days later these values increased equally for all groups to a mean for the cohort of 13.6 + /- 1 gm/dl for hemoglobin and 40.6 % + /- 3 for hematocrit . Serum iron and ferritin were within the normal range . The 200 mg group experienced significantly more side effects ( p < 0.01 ) . CONCLUSION Thus the use of oral iron supplements for the treatment of acute blood loss anemia after uncomplicated coronary artery bypass surgery did not assist in restoring red blood cell mass or help maintain total body iron stores The effectiveness of acupuncture in managing the pain of primary dysmenorrhea was investigated in a r and omized and controlled prospect i ve clinical study . Forty-three women were followed for one year in one of four groups : the Real Acupuncture group was given appropriate acupuncture and the Placebo Acupuncture group was given r and om point acupuncture on a weekly basis for three menstrual cycles ; the St and ard Control group was followed without medical or acupuncture intervention ; the Visitation Control group had monthly nonacupuncture visits with the project physician for three cycles . In the Real Acupuncture group , 10 of 11 ( 90.9 % ) women showed improvement ; in the Placebo Acupuncture group , 4 of 11 ( 36.4 % ) ; in the St and ard Control group , 2 of 11 ( 18.2 % ) ; and in the Visitation Control group 1 of 10 ( 10 % ) . There was a 41 % reduction of analgesis medication used by the women in the Real Acupuncture group after their treatment series , and no change or increased use of medication seen in the other groups Study Design . A r and omized controlled trial was conducted . Objective . To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain . Summary of Background Data . Osteopathic manipulative treatment may be useful for acute or subacute low back pain . However , its role in chronic low back pain is unclear . Methods . This trial was conducted in a university-based clinic from 2000 through 2001 . Of the 199 subjects who responded to recruitment procedures , 91 met the eligibility criteria . They were r and omized , with 82 patients completing the 1-month follow-up evaluation , 71 completing the 3-month evaluation , and 66 completing the 6-month evaluation . The subjects were r and omized to osteopathic manipulative treatment , sham manipulation , or a no-intervention control group , and they were allowed to continue their usual care for low back pain . The main outcomes included the SF-36 Health Survey , a 10-cm visual analog scale for overall back pain , the Rol and –Morris Disability Question naire , lost work or school days because of back pain , and satisfaction with back care . Results . As compared with the no-intervention control subjects , the patients who received osteopathic manipulative treatment reported greater improvements in back pain , greater satisfaction with back care throughout the trial , better physical functioning and mental health at 1 month , and fewer cotreatments at 6 months . The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects . There were no significant benefits with osteopathic manipulative treatment , as compared with sham manipulation . Conclusions . Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain . It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment , such as range of motion activities or time spent interacting with patients , which may represent placebo effects Accumulating research has shown that some cognitive deficits in recently abstinent alcoholics ( e.g. , cognitive flexibility , acquisition of novel skills ) improve only with remediation in contrast to the spontaneous , time-dependent rebound seen for other tasks . In principle , this facilitated or experience-dependent recovery should enhance acquisition of the content of alcoholism treatment programs , but this relationship has yet to be tested empirically ; previous research assessed recovery using only neuropsychological tasks presented by an experimenter . The current investigation focused on treatment-relevant remediation ( acquisition of the content of a relapse-prevention [ RP ] program ) using tasks administered by self-guided workbooks . Four groups of male alcoholics received pre- and posttesting . Between the two testing sessions , the groups received neuropsychological remediation tasks ( n = 15 ) , ecologically relevant tasks ( n = 15 ) , attention-placebo tasks ( n = 16 ) , or no intervention ( n = 15 ) . Results showed that exposure to both types of remediation produced significant cognitive recovery , with skills transferring to posttest neuropsychological measures and RP acquisition . Hence , cognitive remediation may facilitate alcoholism treatment OBJECTIVES To evaluate the efficacy of transcutaneous electrical nerve stimulation ( TENS ) as analgesia during colonoscopy . DESIGN In a r and omised controlled trial , patients undergoing diagnostic colonoscopy were assigned to one of three groups : st and ard medication only ( midazolam ) ; active TENS plus st and ard medication ; or non-functioning TENS and st and ard medication . Efficacy of TENS was determined using numerical rating scores for pain and the post-procedural evaluation question naire . SETTING Patients undergoing diagnostic colonoscopy in a teaching hospital . MAIN OUTCOME There was no statistically significant differences between the three groups . However in the active TENS group there was a greater variation in “ physical discomfort ” and “ psychological distress ” , suggesting TENS may be effective in subgroup of patients Sixty-three episodes of genital herpetic infection in 55 men and 45 episodes in 42 women were r and omly assigned to topical treatment with 3 % adenine arabinoside , topical treatment with placebo ointment , or no therapy . In addition , 10 episodes in women who were not r and omly assigned to therapy were evaluated and followed . Clinical evaluation and viral cultures were done on day 3 , day 8 , and weekly thereafter until the lesions had healed . The natural clinical course of genital herpetic infection was defined in patients given placebo or no therapy . Patients with a history of previous genital herpetic infection had significantly less pain , few lesions , and shorter duration of illness and viral shedding than patients who had no history of previous genital infection with Herpesvirus . An unexpected finding was that 87 % of women experiencing their first episode of genital herpetic infection had cervical cultures positive for Herpesvirus hominis , whereas only 4 % of women with recurrent herpetic infection had a positive cervical culture . Treatment with 3 % adenine arabinoside did not influence the course of either primary or recurrent genital infection with Herpesvirus 5 % Amlexanox oral paste ( Aphthasol ) was studied in four vehicle-controlled , r and omized , double-blind , parallel group , multicenter , clinical studies involving 1335 subjects who had 1 to 3 aphthous ulcers less than 48 hours old at enrollment . Subjects applied study pastes directly to ulcers four times a day until ulcers healed or for the duration of the study , whichever occurred first . Ulcer size was measured by the investigator and pain was evaluated by the subject ; the primary determinant of efficacy was the percentage of subjects with complete healing of ulcers and complete resolution of ulcer pain . The vehicle had marginal beneficial effects as would be expected from a covering material , but statistical significance over no treatment was inconsistent . However , these studies , both individually and collectively , clearly demonstrated in a highly significant and consistent manner that in comparison to both Vehicle and No Treatment 5 % Amlexanox oral paste accelerates the resolution of pain and healing of aphthous ulcers OBJECTIVE To test effectiveness of static magnetic fields of two different configurations , produced by magnetic sleep pads , as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia . DESIGN R and omized , placebo-controlled , 6-month trial conducted from November 1997 through December 1998 . SETTING AND SUBJECTS Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic . INTERVENTIONS Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low , uniform static magnetic field of negative polarity . Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity . Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets ; these groups were combined for analysis . Subjects in the Usual Care group continued with their established treatment regimens . OUTCOME MEASURES Primary outcomes were the change scores at 6 months in the following measures : functional status ( Fibromyalgia Impact Question naire ) , pain intensity ratings , tender point count , and a tender point pain intensity score . RESULTS There was a significant difference among groups in pain intensity ratings ( p = 0.03 ) , with Functional Pad A group showing the greatest reduction from baseline at 6 months . All four groups showed a decline in number of tender points , but differences among the groups were not significant ( p = 0.72 ) . The functional pad groups showed the largest decline in total tender point pain intensity , but overall differences were not significant ( p = 0.25 ) . Improvement in functional status was greatest in the functional pad groups , but differences among groups were not significant ( p = 0.23 ) . CONCLUSIONS Although the functional pad groups showed improvements in functional status , pain intensity level , tender point count , and tender point intensity after 6 months of treatment , with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group The purpose of the study is to investigate the effectiveness of acupressure on fatigue in patients with end-stage renal-disease ( ESRD ) . The study was a r and omized control trial ; qualified patients were r and omly assigned into acupressure group , sham group or control group . A total of 106 participants were included in the study . The measures included the revised Piper Fatigue Scale ( PFS ) , VAS of Fatigue , the Pittsburgh Sleep Quality Index and the Beck Depression Inventory . Data of fatigue measures were collected at pretreatment and a week following treatment . Sleep quality and depression were collected during post-test only . The statistical methods included the descriptive statistics , one-way ANOVA , ANCOVA , and repeated- measures ANOVA . ANCOVA that adjusted for differences in baseline fatigue scores ( PFS ) , post-test of depression and sleep quality , result was significant , F(2,100)=3.99 , p=0.02 . Post-hoc tests revealed that patients in the acupressure group were significantly having lower scores of fatigue than patients in the control group . ANCOVA results also significant for VAS of Fatigue among groups , F(2,100)=5.63 , p=0.003 . Comparisons indicated that there were significant differences between the acupressure group and the control group ( p=0.01 ) and between the sham group and control group ( p=0.003 ) . Predialysis fatigue was assessed routinely by using a rating of 0 - 10 . Repeated- measures ANOVA results demonstrate the group main effect was significant in the perceived fatigue ( F(2,88)=19.46 , p<0.001 ) . Follow-up tests indicated there were significant differences between the acupressure group and the control group ( p<0.001 ) and between the sham group and control group ( p<0.001 ) . The study provided an alternative method for health care providers to managing ESRD patients with fatigue 67 adult women with a history of recurrent lower urinary tract infection ( UTI ) were r and omized for acupuncture treatment , sham acupuncture , or no treatment . The incidence rate of UTI over the following six months was noted . In the acupuncture group a total of 85 % was free of cystitis during the six-month observational period , as compared to 58 % in the sham group ( p < 0.05 ) , and 36 % in the control group ( p < 0.01 ) . Compared to the acupuncture group , twice as many incidents of cytitis occurred in the sham group , and three times as many in the control group ( p < 0.05 ) . Acupuncture seems a worthwhile alternative in the prevention of frequently recurring cystitis in women Two hundred and ten subjects entered a trial to test the use of a chewing gum containing nicotine as an aid to stopping smoking . They were divided into three groups : nicotine chewing gum , placebo chewing gum , and control . The trial was double blind between the two chewing gum groups . After 1 month the percentage of confirmed non-smokers in the nicotine gum group was 34 % , in placebo chewing gum group 37 % and the control group 24 % . By 6 months most of the non-smokers had relapsed , but the nicotine gum group ( 23 % ) was more successful than the placebo ( 5 % or the control group ( 14 % ) Abstract A study by Turner and Ascher ( 1978 ) compared the efficacy of progressive relaxation , stimulus control , and paradoxical intention in ameliorating sleep onset insomnia . Results indicated that the three were equally effective . The present study is a partial replication of Turner and Ascher ( 1978 ) and focuses on the use of paradoxical intention in reducing sleep difficulties . Twenty-five individuals complaining of sleep discomfort were r and omly assigned to three groups : paradoxical intention , placebo control , no treatment control . Clients in the paradoxical intention group were instructed to remain awake while lying in bed in a darkened room . The complete rationale for such a prescription was provided . Those in the placebo group received a pseudo systematic desensitization program . Results indicated that subjects exposed to the paradoxical intention procedure reported significant improvement on several measures of sleep behavior when compared with reports of subjects in either placebo or no-treatment control groups Enhancing hope in people with a first recurrence of cancer Research ers and clinicians have identified the need for well-defined intervention studies to test the efficacy of interventions design ed to strengthen hope . This quasi-experimental study sought to determine if a specific nursing intervention program design ed to enhance hope would positively influence levels of hope and quality -of-life ( QOL ) in a convenience sample of 115 people with a first recurrence of cancer who were r and omly assigned to one of three groups : treatment group ( hope ) , attention control group ( informational ) , or control group ( usual treatment ) . The Herth Hope Index ( HHI ) and the Cancer Rehabilitation and Evaluation Systems , Short Form ( CARES-SF ) were administered prior to intervention , immediately after intervention and at 3 , 6 , and 9-month intervals . Treatment and control groups differed significantly with regard to level of hope ( P=0.02 ) and QOL ( P=0.03 ) . Both the level of hope and QOL were significantly increased ( P=0.03 ) immediately after intervention and across time ( 3 , 6 and 9 months ) . This study was a preliminary attempt to design , implement , and evaluate a theory-driven hope intervention program . Knowledge about the effectiveness of specific interventions design ed to enhance hope is vital if nurses are to significantly influence hope in those whom are in their care Self-referred subjects ( N = 227 ) thought to be at increased risk of developing diabetes who had fasting plasma glucose ( FPG ) values in the range of 5.5 to 7.7 mmol . L-1 on two consecutive occasions 2 weeks apart were r and omized to sulfonylurea therapy ( gliclazide , < or = 160 mg.d-1 ) or to a control group allocated either to double-blind placebo or to no tablets . Subjects were r and omly allocated also to reinforced or basic healthy-living advice in a factorial design . A total of 201 subjects have been evaluated for 1 year in three English and two French hospital outpatient centers . Those allocated to sulfonylurea had a significant ( P < .001 ) reduction in median FPG compared with the control group ( 6.0 mmol . L-1 to 5.6 mmol . L-1 , P < .001 , v 6.0 mmol . L-1 to 6.0 mmol . L-1 , NS ) . Median hemoglobin A1c ( HbA1c ) also improved ( P < .0002 ; 5.8 % to 5.6 % , P < .001 , v 5.7 % to 5.6 % , NS ) , as did mean beta-cell function ( 62 % to 70 % , P < .01 , v 62 % to 61 % , NS ) . Mean body weight was unchanged in subjects allocated to sulfonylurea ( 81.7 kg to 82.4 kg , NS ) , but decreased in the control group ( 81.6 kg to 80.4 kg , P < .01 ) . More subjects in the sulfonylurea group versus the control group reported one or more minor symptoms of hypoglycemia over 1 year ( 50 % v 24 % , P < .0001 ) . Only two subjects reported major hypoglycemic episodes requiring assistance , both of whom were taking sulfonylurea . Insulin sensitivity did not change between groups . Sulfonylurea therapy with gliclazide improved glycemic control and beta-cell function significantly in subjects with increased but not diabetic FPG levels . The study is being extended to determine whether sulfonylurea therapy prevents progression to non-insulin-dependent diabetes mellitus ( NIDDM ) This prospect i ve controlled trial investigated the efficacy of a manual-based clinical hypnosis intervention in alleviating pain in 80 pediatric cancer patients ( 6–16 years of age ) undergoing regular lumbar punctures . Patients were r and omly assigned to 1 of 4 groups : direct hypnosis with st and ard medical treatment , indirect hypnosis with st and ard medical treatment , attention control with st and ard medical treatment , and st and ard medical treatment alone . Patients in the hypnosis groups reported less pain and anxiety and were rated as demonstrating less behavioral distress than those in the control groups . Direct and indirect suggestions were equally effective , and the level of hypnotizability was significantly associated with treatment benefit in the hypnosis groups . Therapeutic benefit de grade d when patients were switched to self-hypnosis . The study indicates that hypnosis is effective in preparing pediatric oncology patients for lumbar puncture , but the presence of the therapist may be critical OBJECTIVE To examine the effects of stress-management training on clinical outcomes in persons with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 141 ) were r and omly assigned to 1 of 3 groups : a stress management group , an attention control group , or a st and ard care control group . The stress management and the attention control groups received a 10-week intervention followed by an additional 15-month maintenance phase . RESULTS The stress management group showed statistically significant improvements on measures of helplessness , self-efficacy , coping , pain , and health status . Selected beneficial effects were still detectable at the 15-month followup evaluation . CONCLUSION The data indicated that stress management interventions are capable of producing important clinical benefits for persons with RA BACKGROUND Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment . There is now in vivo evidence for increased epidermal hydrogen peroxide ( H(2)O(2 ) ) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy ( FT Raman ) . Epidermal H(2)O(2 ) can be removed with a topical application of narrow b and UVB activated pseudocatalase cream ( PC-KUS ) . ( Mn/EDTA-bicarbonate complex , patent No. EPO 58471 1 A ) , yielding initiation of repigmentation . Dead Sea climatotherapy is another successful treatment modality for vitiligo , but the mode of action has escaped definition so far . METHODS Epidermal hydrogen peroxide ( H(2)O(2 ) ) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy . The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream ( PC-KUS ) as well as Dead Sea climatotherapy/placebo cream . Clinical repigmentation was documented by st and ardized black/white photography using non-UV coated bulbs as flashlight and by color photography . RESULTS This study on 59 patients who had vitiligo for an average time of 17 years ( range 3 - 53 years ) confirmed in vivo H(2)O(2 ) accumulation in mM concentrations in the epidermis of untreated patients . Furthermore , we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing , but the decrease of epidermal H(2)O(2 ) levels was significantly less compared to narrowb and UVB activated pseudocatalase cream ( PC-KUS ) . Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy ( 8 - 14 weeks ) and Dead Sea climatotherapy alone ( 5 - 6 weeks ) . CONCLUSION The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy ( 21 days ) at the Dead Sea in combination with a pseudocatalase cream ( PC-KUS ) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy . This combined therapy is significantly faster in repigmentation than narrowb and UVB activated pseudocatalase cream ( PC-KUS ) treatment alone . The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo & NA ; A total of 104 men who were heavy smokers ( minimum of a pack , and averaging 35 cigarettes a day ) participated in a 10‐week program to break the habit . The majority ( N=83 ) received group therapy , and the remainder were seen individually . Each S was r and omly assigned to one of the following drug conditions : no pills , placebo , lobeline , dextroamphetamine and imipramine . Pretesting established each S as a good ( N=67 ) or poor ( N=37 ) risk to stop smoking . Results indicated that , both at the end of treatment and at followup 3 months later , group was superior to individual therapy , treatment without drugs was more effective than taking medication ( especially for high risk cases ) , and low‐risk did better than high‐risk Ss . Successful Ss stayed in treatment longer than did failures . Relapse was associated with life situations of loneliness , passivity , boredom , tension and personal tragedy . The best predictor of resistance to relapse was the abrupt and complete breaking of the habit during the first 2 weeks of the program ( " cold turkey " ) The value of therapeutic ultrasound ( US ) for reducing inflammation was tested in a double-blind controlled study in 150 patients following surgical removal of impacted lower third molars . Facial swelling , trismus , pain and serum C-reactive protein ( CRP ) were significantly reduced in the US-treated groups and in a placebo group ( ' mock ' US ) compared with an untreated control group . The majority of the anti-inflammatory activity was attributable to the placebo effect , and the highest intensity of US ( 1.5 W.cm-2 ) was consistently less beneficial than the lower intensities ( 0.1 and 0.5 W.cm-2 ) and the mock US The involvement of the microcirculation in diabetic microangiopathy ( DM ) causes of severe incapacitation and ulceration . DM is characterized by a diffuse increase in flux , reduction in venoarteriolar response , associated with increased permeability result ing in edema and altered function of microlymphatics . In DM , skin PO2 is decreased and CO2 increased . In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers . The aim of this r and omized , placebo-controlled study was to evaluate the effect of local ( foot ) treatment with Essaven gel ( EG ) in 35 subjects with DM and neuropathy and localized , small ( < 0.5 cm in maximum diameter ) ulcers treated for 2 weeks . Measurements of laser Doppler ( LDF ) flux , PO 2 , and PCO2 in st and ardized conditions showed positive microcir culatory changes ( a significant decrease of the abnormally increased flux and CO2 white PO 2 increased ) in the active EG group . Changes in the control group were not significant . In the placebo group variations were limited ( mainly associated with skin manipulation and gel appli cation ) . In conclusion , local treatment for 2 weeks with st and ardized application of EG acutely improves the microcirculation in subjects with DM and small ulceration The antiemetic action of stimulation of the P6 ( Neiguan ) acupuncture ( ACP ) point has been studied in women , premedicated with nalbuphine 10 mg , undergoing minor gynaecological operations under methohexitone-nitrous oxide-oxygen anaesthesia . Invasive ACP -- manual or electrical at 10 Hz -- applied for 5 min at the time of administration of the premedication markedly reduced the incidence of vomiting and nausea in the first 6 h after operation , compared with untreated controls . This did not occur with stimulation of a " dummy " ACP point outside the recognized ACP meridians . Non-invasive methods ( stimulation via a conducting stud or by pressure ) were equally as effective as invasive ACP during the early postoperative period . However , both these non-invasive approaches were less effective than invasive ACP in the 1 - 6 h postoperative period , although each was as effective as two st and ard antiemetics ( cyclizine 50 mg , metoclopramide 10 mg ) . In view of the total absence of any side effects in more than 500 ACP procedures , the clinical applications of this finding are worthy of further study This paper summarises findings from a study of maintenance treatment in predominantly neurotic depressive responding to initial treatment with amitriptyline . Patients were continued on amitriptyline for eight months , withdrawn double-blind to placebo after two months , or withdrawn overtly to no medication , with and without individual psychotherapy from social workers in the factorial design . Continuation significantly reduced early relapse and symptom return , compared with either condition of early withdrawal . Psychotherapy improved social adjustment after eight months in patients who did not relapse , without any significant interactions . Side effects were minimal , except for carbohydrate craving . These findings suggest that tricyclic antidepressants should be routinely continued for several months after drug-induced remission BACKGROUND Acupuncture has traditionally been used in China in the treatment of bronchial asthma and is being increasingly applied in Western countries . Although there are many published studies on acupuncture and asthma , few meet the scientific criteria necessary to prove the effectiveness of acupuncture . OBJECTIVE To examine the short- and long-term effects of real versus sham or no acupuncture in patients with bronchial asthma . DESIGN R and omized partially blinded study with three parallel groups . SUBJECTS Sixty-six ( 66 ) patients of both genders ( mean age , 39 years ) with mild-to-moderate persistent bronchial asthma . INTERVENTIONS After 2 weeks of run-in , the patients with asthma were r and omized to receive either real ( 23 patients ) or sham acupuncture ( 23 patients ) or no acupuncture ( 20 patients ) . Two acupuncture periods ( each 4 weeks ) within the first 4 months were followed by a 6-month observation . MEASUREMENTS Primary outcome was the change of peak expiratory flow ( PEF ) variability at the end of the two treatment periods . Secondary outcomes were changes in forced expiratory volume in 1 second ( FEV1 ) , airway responsiveness , symptoms of asthma , the use of asthma drugs , and patients ' well-being . Moreover , the effect of the intervention on eosinophils and eosinophil cationic protein ( ECP ) in blood and sputum was assessed . RESULTS PEF variability decreased in all groups . In a subgroup of patients whose asthma medication remained fairly unchanged , PEF variability decreased significantly after needling of real as well as sham points at month 4 and 5 compared to controls ( p < or = 0.005 ) . However , there was no difference in the decrease of PEF variability between patients who had the blinded treatment with real or sham acupuncture . Most of the other functional and clinical variables did not differ from those obtained in controls . Eosinophils and ECP in blood and sputum decreased in all groups , but the only significant differences were found in blood eosinophil count at 4 months between sham acupuncture and the control group ( p < 0.05 ) and at 10 months between real and sham acupuncture ( p < 0.05 ) suggesting a possible effect on eosinophilic inflammation . CONCLUSIONS In view of the fact that the effects after real and sham acupuncture compared to controls who had no needling at all were small , in all likelihood clinical ly irrelevant , our data do not seem to support the use of acupuncture in the management of pharmacologically well-treated patients with mild-to-moderate persistent asthma Transcutaneous electrical nerve stimulation ( TENS ) was assessed for its effect on periodontal pain associated with orthodontic separation . Forty-five adult subjects were r and omly assigned to a TENS group , a placebo TENS group , and a control group . They were further subdivided into intraoral and extraoral electrode placement , and 1- , 2- , and 3-day treatment duration groups . In each patient orthodontic separators were placed mesial and distal to the upper first molars , bilaterally . Subjects were asked to rate their discomfort every 12 hours for 4 days with a 10 cm visual analogue scale . The results showed a significant decrease in reported pain for those subjects in the TENS group at the 24- , 36- , and 48-hour assessment periods as compared to either the placebo or control group . In the control group postseparation discomfort continued through the 60-hour assessment period . The present study suggests that TENS is an effective nonpharmacologic method of controlling postadjustment tooth pain OBJECTIVE To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis ( RA ) . METHODS Subjects ( n = 54 ) with confirmed diagnoses of both major depression and RA were r and omly assigned to 1 of 3 groups : 1 ) cognitive-behavioral/pharmacologic group ( CB-PHARM ) , 2 ) attention-control/pharmacologic group , or 3 ) pharmacologic control group . Measures of depression , psychosocial status , health status , pain , and disease activity were collected at baseline , posttreatment ( 10 weeks ) , 6-month followup , and 15-month followup . Data were analyzed to compare the treatment effectiveness of the groups ; data also were aggregated to examine the effects of antidepressive medication over time . Lastly , a no-treatment control group was defined from a cohort of persons who declined participation . RESULTS Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education ; baseline scores on dependent measures also were entered as covariates . Analyses of covariance revealed no statistically significant group differences at postintervention , 6-month followup , or 15-month followup , except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup . In the longitudinal analyses of the effects of antidepressive medication , significant improvement in psychological status and health status were found at posttreatment , 6-month followup , and 15-month followup , but no significant improvements were shown for pain or disease activity . In addition , the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication . CONCLUSION In persons with RA , cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone , but antidepressant intervention was superior to no treatment A double-blind r and omly controlled trial of one particular laxative , Senokot , used in moderate dosage , was carried out on a group of 40 children with severe and persistent soiling and often with a history of faecal retention . Significant improvement occurred following three months of outpatient treatment using a behavioural approach and either Senokot , placebo or no medication . However , there was no evidence either during the trial or subsequently when Senokot was employed to supplement behavioural treatment in every child who continued with therapy that this laxative contributed in any way to relieving the problem in this group of cases OBJECTIVE In several large , well- design ed , r and omized , double-blind studies , the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence . Specifically , when combined with certain psychosocial therapies , naltrexone reduces the number of drinking days , heavy drinking , and time to relapse to alcohol use in alcohol-dependent individuals . Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established . METHODS A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were r and omized to receive naltrexone 50 mg daily plus usual program treatment ( n = 54 ) , placebo plus usual treatment ( n = 43 ) , or usual treatment alone ( n = 48 ) for 12 week . A total of 133 participants had at least one follow-up visit . Primary outcome measures included percent days drinking , average drinks per drinking day , average drinks per day , heavy drinking days ( four or more for women and six or more for men ) , and time to first heavy drinking day . Secondary measures included changes in serum biological markers ( alkaline phosphatase , alanine transaminase , aspartate transaminase , and gamma-glutamyltransferase ) , craving , and psychosocial functioning . RESULTS In the intention-to-treat analysis , there were no between-group differences for any of the primary drinking outcomes at 12 weeks . In post hoc exploratory analyses , the entire sample of participants was divided into two new groups : ( 1 ) people who drank during the 2 weeks before the start of medication ( entry drinkers ) and ( 2 ) people who did not drink during this interval ( entry abstainers ) . Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment . Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking , average drinks per drinking day , average drinks per day , heavy drinking days , and time to first heavy drinking day . Participants in any of the r and omized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures . The abstainer groups that were r and omized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups . However , for the naltrexone-treated group , entry drinkers and entry abstainers had similar improvement in drinking-related outcomes . CONCLUSIONS These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry Little is known about placebo effects with scientific precision . Poor methodology has confounded our underst and ing of the magnitude and even the existence of the placebo effect . Investigating placebo effects presents special research challenges including : the design of appropriate controls for study ing placebo effects including separating such effects from natural history and regression to the mean , the need for large sample sizes to capture expected small effects , and the need to underst and such potential effects from a patient 's perspective . This article summarizes the methodology of an ongoing NIH-funded r and omized controlled trial aim ed at investigating whether the placebo effect in irritable bowel syndrome ( IBS ) exists and whether the magnitude of such an effect can be manipulated to vary in a manner analogous to " dose dependence . " The trial also uses an innovative combination of quantitative and qualitative methods The purpose of the study is to test the effectiveness of acupressure on sleep quality of end-stage renal disease patients . The study was a r and omized controlled trial ; qualified patients in the dialysis centers of four major hospitals were r and omly assigned into an acupressure group , a sham acupressure group , and a control group . A total of 98 participants were included in the study . The main outcomes measured were the Pittsburgh sleep quality index ( PSQI ) and the sleep log . Data were collected at pretreatment and following treatment . Primary statistical analysis was by means of Analysis of Covariance , the Kruskal-Wallis Test and repeated measure ANOVA . The results indicated that PSQI scores of the acupressure group have a significantly greater improvement ( p < 0.01 ) than the control group . However , there were no differences between the acupressure group and the sham group or the sham group and the control group ( p > 0.05 ) . Subscales of PSQI were further analyzed . Results demonstrated significant differences between the acupressure group and the control group in subjective sleep quality ( p = 0.009 ) , sleep duration ( p = 0.004 ) , habitual sleep efficiency ( p = 0.001 ) , and sleep sufficiency ( p = 0.004 ) . Significant differences in the subscale of subjective sleep quality ( p = 0.003 ) between the sham acupressure group and the control group were also observed . Sleep log data showed that the acupressure group significantly decreased awake time and improved quality of sleep over time more than the control group ( p < 0.01 ) . The improvement could be seen as soon as the acupoints massage was implemented , and it was maintained through the post intervention Thirty-one patients receiving medical treatment for essential hypertension were r and omly distributed into three groups : ( 1 ) relaxation therapy , ( 2 ) nonspecific therapy , and ( 3 ) medical treatment only . The nonspecific therapy group spent the same amount of time with the therapists as the relaxation group but was not given a specific therapy . Blood pressures were measured at a different time and in a different place from the behavioral treatments . The relaxation therapy group showed a significant reduction in blood pressure postreatment compared with the nonspecific therapy and medical treatment only groups , even when those patients whose medication was increased were excluded from the data analysis . At follow-up six months post-treatment , the relaxation group showed a slight decrement in treatment effects , while both the nonspecific therapy and medical treatment only groups showed continued improvement ; thus , there was not a significant difference between groups A single-blind , r and omized clinical trial of 56 female subjects was conducted to determine whether decreased consumption of caffeine decreases breast pain/tenderness or nodularity in patients with suspected benign proliferative breast disease . The subjects were r and omly assigned to one of three groups -- a control group ( no dietary restrictions ) , a placebo group ( cholesterol-free diet ) , and an experimental group ( caffeine-free diet ) . At the initial examination , the subjects reported on the presence of breast pain , the degree to which pain affects daily activities , the frequency of pain , the degree of pain associated with breast examinations , and the degree of pain associated with close-fitting clothing . Subjects were then examined and the four quadrants of each breast were rated on a scale of 0 to 3 ( 0 = normal , fatty tissue , 1 = little seedy bumps or fine nodularity , 2 = discrete nodules or ropy tissue , 3 = confluent areas , hard or soft masses ) . Subjects in all three groups returned for 2- and 4-month follow-up examinations . Total nodularity scores , degree of pain/tenderness , and compliance with dietary restrictions were analyzed . The data showed that decreased caffeine consumption did not result in a significant reduction of palpable breast nodules or in a lessening of breast pain/tenderness & NA ; The present study describes a 16‐week trial of the use of a combination of biofeedback and relaxation techniques for the treatment of hypertension . Twenty‐two hypertensive patients were r and omly allocated to one of three groups : ( 1 ) diastolic blood pressure feedback , electromyographic feedback , and verbal relaxation ; ( 2 ) sham blood pressure feedback ; and ( 3 ) no treatment . For the 14 patients completing active treatment during an initial or crossover period , the average changes in blood pressure as measured outside the laboratory were minimal ( 0/−1 and + 1/0 mm Hg , supine and st and ing , respectively ) . Average blood pressure reduction in the laboratory was no greater with active than with sham blood pressure feedback ( −3/−2 vs. −5/−2 mm Hg ) . One subject , however , after showing no change in blood pressure during sham feedback , achieved pronounced and prolonged improvement following active treatment . Overall results do not support the usefulness of these techniques as primary therapy in most hypertensives The role of mycoplasmas in infertility was studied in 120 couples . During the twelve months of the study 27 couples ( 22 - 5 % ) conceived . T mycoplasmas were isolated from 63 % of these couples , and Mycoplasma hominis from 18 % , compared with 56 % and 13 % , respectively , in those who did not conceive . 88 , with primary infertility of unascertained cause , took part in a controlled trial with doxycycline . The couples in the trial were allocated r and omly to three groups : 30 received doxycycline , 28 received a placebo , and 30 couples were untreated . Although a twenty-eight-day course of doxycycline eradicated M. hominis and T-strain mycoplasmas from 27 ( 96 % ) of the 28 couples harbouring them , the rate of conception was no higher in those treated with the drug than in control groups . It is concluded that mycoplasmas are not associated with primary infertility and that , although doxycycline eradicates them , this drug is of no benefit in the treatment of primary infertility of unascertained cause PURPOSE To evaluate the effects of r and omly assigning smokers who have early chronic obstructive pulmonary disease ( COPD ) to a smoking-cessation intervention on the symptoms of chronic cough , chronic phlegm production , wheezing and shortness of breath , and to determine the effects of quitting smoking on these symptoms . SUBJECTS AND METHODS A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [ defined as a forced expiratory volume in the first second ( FEV1 ) of 55 % to 90 % of predicted and FEV1/forced vital capacity ( FVC ) < 0.70 ] were enrolled in a 5-year clinical trial . Two-thirds of participants were r and omly assigned to smoking-intervention groups and one-third to a usual-care group . The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum . One intervention group was treated with ipratropium bromide by inhaler ; the other intervention group received placebo inhalers . The usual-care group was advised to stop smoking . All participants were followed annually . Smoking status was biochemically vali date d by salivary cotinine measurements or exhaled carbon monoxide values . RESULTS Vali date d 5-year sustained smoking cessation occurred in 22 % of participants in the intervention compared with only 5 % of participants in the usual-care group . At the end of the study , the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group ( P < 0.0001 ) . For example , among participants who did not report cough at baseline , 15 % of those in the intervention groups had cough at least 3 months during the year , compared with 23 % of those in usual care . Sustained quitters had the lowest prevalence of all four symptoms , whereas continuous smokers had the greatest prevalence of these symptoms . Changes in symptoms occurred primarily in the first year after smoking cessation . Respiratory symptoms were associated with greater declines in FEV1 during the study ( P < 0.001 ) . Ipratropium bromide had no long-term effects on respiratory symptoms . CONCLUSIONS In this prospect i ve r and omized trial using an intention-to-treat analysis , smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up BACKGROUND An important parallel exists between patients with seasonal affective disorder and institutionalized older adults . Many older patients , as a result of global physical decline and immobility , are confined to their rooms , experiencing little natural sunlight . Thus , institutionalized older adults are at risk for chronic light deprivation . Testing the hypothesis that chronic light deprivation might be responsible , at least in part , for some depression among institutionalized older adults , the aim of this study was to investigate the efficacy of morning bright light treatment on depression among older adults residing in a long-term care facility . METHODS In a placebo controlled , crossover design , participants ( N = 10 , six women and four men ; M age = 83.8 ) received each of the following : ( i ) 1 week ( 5 days ) of 10,000 lux ( therapeutic dose ) ; ( ii ) 1 week ( 5 days ) of 300 lux ( placebo ) ; or 1 week of no treatment ( control ) . Each week of light treatment was 5 consecutive days , 30 minutes daily , with a wash-out period consisting of 1 week between conditions . RESULTS Geriatric Depression Scale ( GDS ) scores at baseline during all treatment conditions were positively correlated ( r = .81 , p < .01 ) with months of institutionalization , where participants with higher GDS scores experienced more time institutionalized . Scores on the GDS remained unchanged during the placebo and control conditions , but depression scores decreased significantly during the 10,000 lux treatment ( pretest GDS M = 15 vs posttest GDS M = 11 , p < .01 ) . After the 10,000 lux treatment , 50 % of the participants no longer scored in the depressed range . Improvement during the 10,000 lux condition was positively correlated ( r = .62 , p < .05 ) to baseline GDS scores , where participants with higher GDS scores experienced greater improvement following the 10,000 lux treatment . CONCLUSIONS The results of the present study suggest that bright light treatment may be effective among institutionalized older adults , providing nonpharmacological intervention in the treatment of depression . Furthermore , the length of institutionalization may play an important role in determining the efficacy of bright light treatment for older adults in the nursing-home setting AIM Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy . METHODS A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers ( Heidelberg , Frankfurt , Nijmegen ) were treated in this double-blind split-mouth study . In each patient , 3 different treatment modalities were assigned r and omly to 3 test teeth : scaling and root planing alone ( SRP ) , SRP with subgingival vehicle control ( VEH ) , and SRP with subgingival application of a newly developed biodegradable 15 % doxycycline gel ( DOXI ) . At baseline , clinical parameters were measured at all single rooted teeth using a reference splint : PlI , PPD , relative attachment level ( RAL-V ) , GI . 3 strata were generated according to baseline PPD : ( i ) 5 - 6 mm , ( ii ) 7 - 8 mm , ( iii ) > or = 9 mm . Not more than 50 % active smokers were allowed to each stratum . 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites . The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to Huynh & Feldt . The comparison of SRP versus DOXI was considered as the main study question . RESULTS 110 patients finished the 3 months and 108 the 6 months examination . The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel . DOXI provided statistically significantly more favorable PPD reduction ( SRP : -2.4+/-1.4 mm , VEH : -2.7+/-1.6 mm , DOXI : -3.1+/-1.2 mm ; SRP versus DOXI p=0.0001 , VEH versus DOXI p=0.0066 ) and RAL-V gain ( SRP : 1.6+/-1.9 mm , VEH : 1.6+/-2.2 mm , DOXI : 2.0+/-1.7 mm ; SRP versus DOXI p=0.027 , VEH versus DOXI p=0.038 ) than SRP and VEH after 6 months . CONCLUSIONS Adjunctive topical subgingival application of a biodegradable 15 % doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH . Thus , by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets A cognitive remediation intervention was tested for its effect on functional outcomes of older care recipients with the diagnosis of dementia of the Alzbeimer 's type . The 78 community-dwelling care recipients were assessed on cognitive and behavioral functioning and r and omly assigned to one of three conditions . Care recipients were expected to benefit most from active cognitive stimulation training as compared to placebo ( passive ) activity or wait-list control conditions . Following each weekly instruction session , the intervention was executed in the home by the family caregiver . Care recipients in the experimental group improved in cognitive and behavioral performance with treatment , but returned to former level of functioning by the 9th month . In contrast , the control group declined , while the placebo group remained static on these variables . These findings support the viability of remediation interventions in dementia despite the trajectory of cognitive decline AIMS Homeopathic medicines are frequently purchased over the counter ( OTC ) . Respiratory complaints are the most frequent reason for such purchases . Children with upper respiratory tract infection ( URTI ) are frequent users of homeopathy . This study investigates the effect of self treatment with one of three self selected ultramolecular homeopathic medicines for the prevention of childhood URTI . METHODS A double-blind r and omized parallel group placebo controlled trial was carried out in 251 children below the age of 10 years , recruited by post from those previously diagnosed with URTI when attending a casualty department . The children were r and omly assigned to receive either placebo or ultramolecular homeopathic medicines in C-30 potency ( diluted 10(-60 ) ) administered twice weekly for 12 weeks . Parents chose the medicine based on simplified constitutional indications for the three medicines most frequently prescribed by Norwegian homeopaths for this group of patients . The main outcome measure relates to the prevention of new episodes of URTI measured with median total symptom score over 12 weeks . RESULTS There was no difference in the predefined primary outcome between the two groups ( P = 0.733 ) . Median URTI scores over 12 weeks in the homeopathic medicine group were 26.0 ( 95 % confidence interval ( CI ) 16.3 , 43.7 ) and for placebo 25.0 ( 95 % CI 14.2 , 38.4 ) . There was no statistical difference between the two groups in median number of days with URTI symptoms or in the use of conventional medication/care . CONCLUSIONS In this study there was no effect over placebo for self treatment with one of three self selected , ultramolecular homeopathic medicines in preventing childhood URTI . This can be due to the lack of effect of the highly diluted homeopathic medicines or the process of selection and type of medicines OBJECTIVES To study the effect of single-needle acupuncture in suppressing gag-reflex in transesophageal echocardiography ( TEE ) . DESIGN Prospect i ve , blinded trial . Setting s/locations : Patients with ischemic stroke or transient ischemic attack undergoing TEE because of presumed cardioembolic origin in a specialized stroke unit of the Johann Wolfgang Goethe-University , Frankfurt/Main , Germany . Subjects/ Study interventions : Forty-one ( 41 ) patients were studied . Patients received single-needle acupuncture with a 0.2 x 13 mm disposable acupuncture needle ( Suzhou Medical Appliances , China ) , 10-mm deep either at Chengjiang ( midline between lower lip and chin ) or superficially at a sham point ( tip of the chin ) during TEE or no acupuncture for alleviating gag reflex . OUTCOME MEASURES Severity of gagging was rated on a visual-analogue scale . RESULTS The acupuncture group experienced significantly less gagging than the sham group ( p = 0.037 ) or the nonacupuncture group ( p = 0.013 ) . CONCLUSIONS Acupuncture of CV24 is an easy to apply and effective method to reduce gag reflex during TEE Fifty patients recruited with ragweed allergic rhinitis were studied . Twenty-three of these patients had asthma . On the basis of cutaneous end point titration to ragweed , patients were r and omly assigned to polymerized ragweed ( PRW ) , placebo , or untreated groups . PRW patients received the equivalent of 1200 micrograms AgE in 15 weekly injections . All patients were followed through the ragweed season with daily rhinitis symptom-medication diaries . All patients had determinations of IgE against AgE and total ( blocking ) antibody to AgE before and after the injection series . In these patients selected for allergic rhinitis , the presence or absence of asthma did not significantly influence rhinitis symptom-medication scores or the values of immunologic parameters . Moreover , whether or not patients had asthma , those who received PRW had an increase in total AgE binding with no increase in IgE-a-AgE and significantly lower rhinitis scores than those who did not Investigated the effects of psychologically preparing patients for minor gynaecological surgery . A total of 59 women who were undergoing elective laparoscopy were assigned r and omly to three experimental conditions : Preparation , in which an informative preoperative interview was conducted ; placebo , in which a reassuring preoperative interview was held ; and control , in which no contact was made prior to surgery . The women were assessed postoperatively in terms of pain , anxiety and attitudes and required to complete a follow-up question naire that followed a 3-week interval , which assessed subjective report of recovery rate . The results showed similar levels of pain report for all groups , although significantly fewer prepared patients requested postoperative analgesia . No differences in pain reports emerged at follow-up , although there was a tread for prepared patients to report a more rapid return to full health . The results are considered in the context of explanatory models that have been proposed to account for the effects of psychological preparation Two consecutive studies were undertaken to evaluate the effectiveness of acupuncture as an antiemetic used in addition to premedication with opioids in patients undergoing minor gynaecological operations . In the first study 25 of the 50 patients underwent acupuncture immediately after premedication with 100 mg meptazinol , the rest receiving the drug alone , and in the second 75 patients were allocated r and omly to one of three groups : a group receiving 10 mg nalbuphine and acupuncture , a group receiving premedication and dummy acupuncture , and a group receiving premedication alone . Manual needling for five minutes at the P6 acupuncture point ( Neiguan ) result ed in a significant reduction in perioperative nausea and vomiting in the 50 patients who underwent acupuncture compared with the 75 patients who received no acupuncture . These findings can not be explained , but it is recommended that the use of acupuncture as an antiemetic should be explored further The recently completed long-term maintenance trial of full-dose imipramine for recurrent unipolar disorder provided an opportunity to examine the extent to which such doses ( 200 - 300 mg daily ) are associated with persistent and adverse side effects , particularly weight change . In 115 patients we monitored weight change during the three-year maintenance treatment phase to the point of trial completion , recurrence or termination . No differences were noted between individuals receiving active medication ( average gain of 5.8 lbs . during an average treatment period of 725 days ) versus those r and omized to the ' no-drug ' cells ( average gain of 2.8 lbs . during an average treatment period of 422 days ) . Numerous other factors such as body mass index , previous weight gain and gender did not play a differential role in establishing why some individuals gained weight during long-term treatment of depression regardless of specific treatment Most studies dealing with spina bifida children concentrate on medical or physical factors , largely ignoring any psychosocial and educational consequences . The present study assessed the effect of a remedial program on visual-motor perception in spina bifida children . Thirty-six spina bifida boys and girls ( mean age 82.87 months ) with a myelomeningocele and an associated hydrocephalus were assigned r and omly to either a control , attention-placebo , or experimental group . Following the administration of the Frostig Program for the Development of Visual Perception , the experimental group significantly improved on a global index of visual perception and the five subtests of Frostig 's Development Test of Visual Perception ; at a maintenance test two months later , all treatment gains ( except on the visual spatial perception subtest ) were still evident . These results are discussed in terms of the provision of remedial education for spina bifida children , and a possible cognitive mechanism mediating the behavioral change in the experimental group OBJECTIVE To evaluate the cost-effectiveness of two types of advice ( usual and intensive ) to lower cardiovascular risk , with or without pharmacological medication aim ed at lowering cholesterol levels . DESIGN Prospect i ve , r and omized , controlled clinical study of 18 months ' duration . SETTING Thirty-two primary health care centres in Sweden . SUBJECTS A total of 384 males , aged 30 - 59 years , with at least one cardiovascular risk factor in addition to moderate primary hyperlipidaemia ; of these , 355 completed the 18-month follow-up . INTERVENTIONS Intensive advice consisted of group sessions led by a health care professional ; the usual level of advice was given at follow-up visits . The pharmacological intervention consisted of pravastatin . The goal was to achieve a 15 % reduction in cholesterol . MAIN OUTCOME MEASURES Cost per life-year gained based on the change in serum cholesterol and the net intervention cost of the four treatment options . RESULTS The usual level of advice and intensive advice in combination with pharmacological treatment achieved no incremental effects and were not considered in the cost-effectiveness analysis . The cost per life-year gained of pharmacological treatment compared with intensive advice decreased . The cost per life-year gained of pharmacological treatment compared with no treatment was about $ 61,000 , if no adverse consequences on noncardiovascular mortality were assumed . CONCLUSIONS According to the results of the CELL trial , intensive advice is not a cost-effective strategy compared with lipid-lowering drug treatment . However , it is also doubtful whether drug treatment as primary prevention is cost-effective compared with no treatment in the studied patient population The increase in forced expiratory volume in one second ( FEV1 ) seen in asthmatics after inhalation of isotonic saline was studied in a blind , cross-over investigation of 24 consecutive out- patients presenting with reversible chronic airway obstruction . Forced expiratory manoeuvres allowing the measurement of FEV1 and forced vital capacity ( FVC ) were performed at six time intervals during a period of one hour according to the following regimes : inhalation of terbutaline by means of a Pari-inhalier Boy for 10 min ; inhalation of isotonic saline under the same conditions ; inhalation of ambient air under the same conditions ( placebo with noisy nebulizer ) ; inhalation of air without the nebulizer ( non-treatment ) in order to determine whether the impact of treatment by a nebulizer influences the measured lung function . A statistically significant increase in FEV1 was observed after each of the four regimes . The increase was large following terbutaline inhalation . After the other three regimes , it was significantly smaller and of about the same magnitude in each case . The increase in FEV1 after the non-treatment regime was unexpected and could possibly be due to the repeated dynamic spirometry . The increase in FEV1 after isotonic saline and ambient air ( noisy nebulizer ) did not differ from the increase after the non-treatment regime . We conclude that neither isotonic saline nor the impact of treatment with a noisy nebulizer have a measurable effect on lung function Conventional treatments for Major Depression , although reasonably effective , leave many without lasting relief . Alternative approaches would therefore be welcome for both short- and long-term treatment of depression . Thirty-eight women were r and omized to one of three treatment conditions in a double-blind r and omized controlled trial of acupuncture in depression . All participants eventually received eight weeks of acupuncture treatment specifically for depression . From among the 33 women who completed treatment , 26 ( 79 % ) were intertiewed at six-month follow-up . Relapse rates were comparable to those of established treatments , with four of the 17 women ( 24 % ) who achieved full remission at the conclusion of treatment experiencing a relapse six months later . Compared to other empirically vali date d treatments , acupuncture design ed specifically to treat major depression produces results that are comparable in terms of rates of response and of relapse or recurrence . These results suggest a larger trial of acupuncture in the acute- and maintenance-phase treatment of depression is warranted The effect of guar gum ( 15 g/day ) on serum lipids and body weight of middle-aged hypercholesterolemic females was studied in a double-blind controlled trial . No consistent changes were observed in serum cholesterol , triglycerides or HDL cholesterol in patients taking guar gum , placebo or no medication at all . A highly significant decrease in body weight ( 62.9 + /- 2.1 vs. 60.4 + /- 2.2 kg , p < 0.0005 , paired comparison ) was seen in subjects receiving guar gum , whereas body weight remained constant in the other two groups . It is concluded that the daily ingestion of 15 g of guar gum results in a permanent weight loss , but does not influence serum lipids in females with hypercholesterolemia To assess the efficacy of exercise therapy for acute low back pain , a r and omized , placebo-controlled trial was performed in 40 Dutch general practice s. Patients received either exercise instruction with advice for daily life by a physiotherapist ; placebo ultrasound therapy by a physiotherapist ; or usual care by the general practitioner . All patients received analgesic agents and information on low back pain before r and omization . Four hundred seventy-three patients were included . No differences in number of recurrences , functional health status , or medical care usage could be found among the three groups . In the exercise group , duration of recurrences was shorter and patients were less tired during the first 3 months than in the usual care group , but no differences were found between the exercise and placebo groups . It was concluded that exercise therapy for patients with acute low back pain has no advantage over usual care from the general practitioner A prospect i ve r and omised trial was carried out to see whether paranormal healing by laying on of h and s might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal , psychological , or placebo factor . Patients were r and omised to three treatment groups : paranormal healing by laying on of h and s ( n=40 ) , paranormal healing at a distance ( n=37 ) , and no paranormal healing ( controls ; n=38 ) . Healing at a distance and no paranormal healing were investigated double blind . Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 ( mean reduction ( 95 % confidence interval ) 17·1 ( 14·0 to 20·2)/8·3 ( 6·6 to 10·0 ) mm Hg ) . Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different . Each week diastolic pressure was consistently lower ( average 1·9 mm Hg ) after healing at a distance compared with control , but on paired comparison these differences were not significant . Probably week to week variations among the groups accounted for any differences noted . In this study no treatment was consistently better than another and the data can not therefore be taken as evidence of a paranormal effect on blood pressure . Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself Oral immunotherapy ( IT ) was evaluated in a pilot study in two centres in children aged 8–15 years with allergic rhinoconjunctivitis . High doses ( up to 20 × 106 BU monthly ) of a defined freeze‐dried birch pollen extract administered in enteric‐coated gelatine capsules were given either daily for seven consecutive days every month or once weekly . Symptom scores , as assessed by sneezing , dripping and blockage of the nose , and redness , itching and swelling of the eyes , were significantly lower in treated patients compared to untreated , or placebo treated controls after 3 to 5 months of therapy . In all the 16 treated , but only in three of eight untreated patients , the scores were lower during the pollen season 1982 than during the pollen season preceding the treatment period , despite comparable pollen counts during the two seasons . One year after beginning treatment the reactivity in conjunctival provocation tests was decreased about 10‐fold ( P < 0.001 ) in the patients receiving more than 2 × 105 BU monthly compared to about two‐fold in patients receiving lower doses , or placebo . Increased levels of IgE antibodies directed against birch pollen were recorded in the serum and saliva of most patients after 3–4 months of active IT . In contrast , IgG antibody responses were poor in most of the patients . Side effects , particularly from the gastrointestinal tract , appeared in all treated children . In one of t hem a systemic reaction occurred during IT . The study indicates that properly performed oral IT with a potent birch allergen extract in enteric‐coated capsules may be effective 63 pts affected by CIN of various degrees were r and omly divided into 3 groups in order to evaluate the pain experienced during laser vaporization of the lesion . All pts were premenopausal and ages ranged between 19 and 39 years . 21 pts received Naproxene Sodium ( 550 mg ) 30 minutes before surgery ; 21 pts received placebo and 21 pts received no drug . Laser vaporization was performed with a Coherent System 451 CO2 laser with a power setting of 28 W/cm2 and a spot size of 1.8 mm . The severity of pain was assessed by means of a Visual Analogue Scale . The mean VAS value was 19 for the group treated with Naproxene Sodium ; the mean VAS value was 20 for the placebo group and 23 for the group which received no pre-operative drug . Analysis of data from the 3 groups showed no statistically significant difference . Analgesia or anaesthesia before laser surgery for CIN is not a necessity OBJECTIVE To investigate whether individualised treatment by homeopaths is effective in preventing childhood upper respiratory tract infection ( URTI ) . METHODS Open , pragmatic , r and omised parallel-group trial with waiting-list group as control . One hundred and sixty-nine children below the age of 10 years , recruited by post from children previously diagnosed with URTI , were r and omly assigned to receive either pragmatic homeopathic care from one of five homeopaths for 12 weeks or to a waiting-list control using self-selected , conventional health care . RESULT There was a significant difference in median total symptom score in favour of homeopathic care ( 24 points ) compared to the control group ( 44 points ) ( p = 0.026 ) . The difference in the median number of days with URTI symptoms was statistically significant with 8 days in the homeopathic group and 13 days in the control group ( p = 0.006 ) . There was no statistical difference in the use of conventional medication or care between the two groups . CONCLUSION In this study , there was a clinical ly relevant effect of individualised homeopathic care in the prevention of URTI in children This study examined the effects of transcutaneous electrical neroe stimulation ( TENS ) on incisional pain caused by the procedure of cleaning and packing an abdominal surgical wound . Seventy-five subjects ( mean age 56.9 years ) were r and omly assigned to one of three intervention groups : TENS , placebo-TENS , or no-treatment control . The appropriate experimental treatment was administered during the routine dressing change which took place two mornings after surgery . Using an 11-point , visual analogue pain scale , subjects described pain experienced during the dressing change . Subjects who received TENS reported a significantly lower level of pain after dressing change than did those subjects who received either placebo-TENS or no-treatment . Drug administration variables did not contribute significantly to level of reported pain 90 schoolchildren aged twelve and thirteen years kept a dietary diary for three days . In most cases the average intake of vitamins was close to the recommended daily allowance , although for a minority the intake was low ; with minerals the recommended daily allowance was less commonly achieved . To examine the possibility that deficiency of dietary minerals and vitamins was preventing optimum psychological function , a multivitamin/mineral supplement or a placebo was administered double-blind for eight months to 60 of the children . The supplement group , but not the placebo group or the remaining 30 who took no tablets , showed a significant increase in non-verbal intelligence ABSTRACT The purpose of this research was to employ a double-blind placebo control design of ion-tophoretically administered lidocaine to assess the test-retest reliability and validity of a magnitude matching procedure using a pressure algometer . In studies in the literature on assessment of pain in temporom and ibular disorders ( TMD ) , the pressure algometer has been found to be a reliable means of measuring pressure-pain threshold and a sensitive measure of treatment-response in the laboratory . However , previous research with this apparatus has not employed more sophisticated psychophysics . This study employs a magnitude matching psychophysical protocol to obtain a multidimensional pain report . Test-retest reliability over two occasions , 3–8 days apart , was found to be moderate for discrim-inability ( $ = .71 , $ < .01 ) but poor for response bias ( r = .44 ) . The validity study used iontophoresis as an anesthetic in a double-blind placebo and no-treatment control design . Although it was hypothesized that subjects in the anesthesia group would demonstrate reduced discriminability as compared with the control groups , no differences were found among the three groups on this measure . However , differences in response bias were found , with both the placebo control and no-treatment control groups differing from the experimental group but not from each other . Possible explanations and the implication s of these findings are discussed Within 24 hours after abortion , 62 patients with a mean gestational age of 19 weeks , who had either induced ( n = 50 ) or spontaneous ( n = 12 ) abortions were r and omly allocated to three groups : Group 1 , bromocriptine 2.5 mg twice daily for 2 weeks ; Group 2 , placebo tablets 1 tablet twice daily for 2 weeks ; Group 3 , o treatment . Fifty‐two patients completed the study ( bromocriptine n = 18 , placebo n = 18 and no treatment n = 16 ) . Placebo had no apparent influence on breast symptoms . In both the placebo group and the untreated group , breast pain and milk secretion peaked on days 3 to 7 , and milk secretion often continued for 3 weeks . Only 3/34 ( 9 % ) of untreated and placebo treated patients were free of breast symptoms . Compared with placebo , bromocriptine caused a significant reduction in the objective assessment score of breast tenderness ( p < 0.05 ) and milk secretion ( p < 0.011 , in serum prolactin ( PRL ) ( p < 0.001 ) and in the subjective assessment score of breast pain ( p < 0.01 ) and milk secretion ( p < 0.01 ) . Alleviation of breast pain and prevention of milk secretion appears to be indicated after second‐trimester abortion , and treatment with bromocriptine is efficacious Given the inherent side effects associated with both opioid and nonopioid analgesic drugs , a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable . We design ed a shamcontrolled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation ( TAES ) on postoperative patient-controlled analgesia ( PCA ) requirement for hydromorphone ( HM ) , the incidence of opioid-related side effects , and the recovery profile after lower abdominal surgery . One hundred one healthy consenting women undergoing lower abdominal procedures with a st and ardized general anesthetic technique were r and omly assigned to one of four postoperative analgesic treatment regimens : Group I ( n = 26 ) PCA only ; Group II ( n = 25 ) , PCA + sham-TAES ( no electrical stimulation ) ; Group III ( n = 25 ) , PCA + low-TAES ( 4 - 5 mA of electrical stimulation ) ; Group IV ( n = 25 ) , PCA + high-TAES ( 9 - 12 mA of electrical stimulation ) . The PCA device was programmed to deliver HM , 0.2 - 0.4 mg intravenously boluses " on dem and , " with a minimum lockout interval of 10 min . The TAES skin electrodes were placed at the Hegu acupoint on the nondominant h and and on both sides of the surgical incision . The TAES frequency was set in the dense- and -disperse mode , alternating at 2 Hz and 100 Hz every 3 s , with stimulation of the h and and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake . After discontinuation of PCA , oral pain medications were administered on dem and . The postoperative PCA-HM requirement , pain scores , opioid-related side effects , and requirements for antiemetic and antipruritic medication were recorded . High-TAES decreased the HM requirement by 65 % and reduced the duration of PCA therapy , as well as the incidence of nausea , dizziness , and pruritus . Low-TAES produced a 34 % decrease in the HM requirement compared with only 23 % in the " sham " TAES group . We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery . ( Anesth Analg 1997;85:406 - 13 The aim of this study was to evaluate the effect of nursing intervention on hope and quality of life in cancer patients . The sample consisted of 96 newly diagnosed Norwegian cancer patients ages 26 to 78 years , the majority of them women ( 71 % ) . Breast cancer was the predominant type of cancer in this sample . The study used an experimental design in which patients were r and omly allocated to three different groups . The first group was the experimental group , for which the intervention was design ed to increase hope . The second group ( attention control group ) participated in the " Learning to Live with Cancer " program . The last group was a control group . The Nowotny Hope Scale was used to measure hope , and the Ferrans and Powers Quality of Life Index and the Cancer Rehabilitation and Evaluation Systems , short form , were used to measure quality of life . The question naires were completed four times : twice before , then 2 weeks and finally 6 months after the intervention . The level of hope was significantly increased ( p = 0.020 ) for the members of the hope group just after the intervention , but not after 6 months . Despite the patients ' positive evaluation of the intervention , there was no impact on quality of life After an initial four-week baseline phase , during which daily records of headache frequency and intensity and daily medication records were kept , 30 patients with frequent ( at least one per month ) migraine headaches were r and omly assigned to three conditions : ( 1 ) temperature biofeedback , autogenic training , and regular home practice ; ( 2 ) progressive relaxation with regular home practice ; and ( 3 ) a waiting-list control condition . Comparisons of headache data from the four weeks of baseline and last two weeks of treatment showed that both the relaxation and biofeedback groups improved significantly on total headache activity , duration of headaches , and peak headache intensity and reduced consumption of analgesic medication , while the waiting list control group did not . All three groups showed significant decreases in headache frequency . Although the relaxation training was more effective than biofeedback training at the last week of treatment , follow-up data at one , two , and three months showed no differences between the two treated groups on any dependent measure & NA ; A 3 × 6 factorial design with a double blind and placebo control was employed to investigate the effect of TENS treatment on pain produced by venipuncture . The three treatment groups consisted of TENS , placebo‐TENS and control . Subjects were blocked into six 2‐year age groups ( ages : 5–17 years ) . During the period of the study , 896 children attending the outpatient laboratory of a general hospital were screened and 514 children completed the study . The data which were collected before venipuncture included expected pain and state anxiety . Following venipuncture , pain intensity was measured with a vertical visual analogue scale ( VAS ) and pain affect was assessed with McGrath 's faces scale . Significant main effects for treatment and age groups were obtained . Pain intensity and affect were lowest for the TENS group and highest for the control group . The pain scores were greatest for lower age groups and lowest for higher age groups . The results of this study support the use of TENS for children 's pain and the need for interventions for children 's procedural pain OBJECTIVES The sham control is widely used in acupuncture research , and its adequacy may be assessed by exploring the ' credibility ' of the intervention . We aim ed to examine the credibility of the study intervention , to quantify the size of the placebo response and effect of time in reducing nausea in early pregnancy . DESIGN Five hundred and ninety-three women with nausea or vomiting in early pregnancy volunteered to participate in a r and omised controlled trial , conducted at the Women 's and Children 's Hospital , South Australia . OUTCOME MEASURES Women completed the Rhodes Index of Nausea and Vomiting and the Credibility Rating Scale . RESULTS The credibility of the acupuncture and sham acupuncture interventions were not different . The relative change in nausea at the end of the first week of the study was estimated to be 28 % attributed to a time effect and 7 % to the placebo response . At the end of the third week , there was a further small increase in time effect ( 32 % ) and the placebo response ( 17 % ) . CONCLUSION Sham acupuncture is a credible control and allows assessment of the size of the placebo response OBJECTIVE To evaluate the efficacy of Simulated Presence , a personalized approach to enhance well-being among nursing home residents with Alzheimer 's disease and related dementia 's ( ADRD ) . DESIGN Latin-Square , double blinded , 3-factor design with restrictive r and omization of three treatments ( the study intervention , a placebo audio tape of a person reading the newspaper , and usual care ) . The three factors were treatment , time , and facility type . SETTING Nine nursing homes in Eastern Massachusetts and Southern New Hampshire . PARTICIPANTS Fifty-four subjects with documented ADRD who were aged 50 years or older , medically stable , had resided in their current nursing home for at least 3 months , and who had no planned discharge . All subjects had a history of agitated or withdrawn behaviors . INTERVENTION The purpose of Simulated Presence is to provide a personalized intervention for persons with moderate to severe cognitive impairment . Through a unique testing process , some of the best loved memories of the ADRD person 's lifetime are identified and then those memories are introduced to the patient in the format of a telephone conversation using a continuous play audio tape system . The intervention may be used for extended periods of time because each repetition is viewed as a fresh , live telephone call as a result of the short-term memory deficit of the person with ADRD . MEASUREMENTS Direct observations of outcomes included using a newly developed scale , the Scale for the Observation of Agitation in Persons with Dementia , an agitation visual analog scale , the Positive Affect Rating Scale ( mood and " interest " ) , a withdrawal visual analog scale , and facial diagrams of mood . Reported measures included daily staff observation logs of responses to interventions offered , and weekly staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the Multidimensional Observation Scale for Elderly Subjects ( mood and " interest " ) . Severity of dementia was assessed by the Mini-Mental State Exam , the Test for Severe Impairment , the Bedford Alzheimer 's Nursing Scale , and the ADL Self-Performance Scale . RESULTS Chi-square analysis of direct observations , using facial diagrams , revealed that Simulated Presence was equivalent to usual care ( P = .141 ) and superior to placebo for producing a happy facial expression ( P = .001 ) . A positive effect was also documented in nursing staff observation logs using Analysis of Variance techniques ( ANOVA ) for subjects during Simulated Presence phases compared with the placebo phases ( P < .001 ) and usual care phases ( P < .001 ) . According to ANOVA analyses of " interest " from weekly surveys , Simulated Presence was superior to both usual care ( P = .001 ) and placebo ( P = .008 ) . We were unable to find evidence of significant differences ( P < .05 ) among interventions for other direct observations and weekly reports of overall agitation or mood aspects of withdrawal . Subjects accepted the intervention most of the time , except for five subjects who refused it more than 50 % of the time . CONCLUSION This study provided evidence that Simulated Presence can be effective in enhancing well-being and decreasing problem behaviors in the nursing home setting as a substitute for or complement to usual care The expectation of pain is a statistically significant factor negatively affecting patient compliance with current screening flexible sigmoidoscopy recommendations . Numerous pain reduction modalities have been studied with limited success . Transcutaneous electrical nerve stimulation ( TENS ) has been used to treat pain of various origins . The purpose of this pilot study was to determine the efficacy of TENS in reducing discomfort experienced during screening flexible sigmoidoscopy . A double-blind study was conducted in which 90 subjects were r and omized to receive TENS , sham TENS , or control ( st and ard care ) . The same pulse frequency and intensity were used for all subjects in the TENS group . Subjects completed preprocedural and postprocedural question naires , and the endoscopist completed a postprocedural question naire . A slight , but statistically insignificant ( p = .526 ) reduction in the mean pain score reported by the TENS group was noted when compared with the sham TENS and control groups ( 2.00 , 2.27 , and 2.23 respectively ) . In light of the fact that only one pulse frequency and intensity of the TENS intervention were used in this study , further study with this safe and cost-effective modality is warranted Both disulfiram and placebo implant patients abstained longer and had more intense disulfiram-ethanol reactions than did two control groups BACKGROUND Unpleasant blood donation-related symptoms may discourage otherwise healthy , altruistic individuals from becoming repeat donors . This study examined a behavioral technique called applied muscle tension ( AMT ) that might reduce reactions . STUDY DESIGN AND METHODS A total of 605 donors at mobile clinics were assigned to either an AMT treatment condition , a no-treatment control condition , or a placebo control condition . AMT involves repeated tensing of major muscles and was taught using an instructional video . Participants in the placebo control group watched the same video but were told to practice the technique only from the time they got on the donation chair until insertion of the needle , without being told that reactions are unlikely during this period . RESULTS There were no differences between men assigned to the three conditions . Women donors assigned to the AMT condition reported significantly fewer donation-related symptoms , required less chair reclining for reactions , and were more likely to produce a full unit of blood than women in both the no-treatment and placebo control conditions . Women in the AMT condition also said they would be more likely to recommend it to a friend who was going to give blood , but there were no significant effects of AMT on the rated probability of giving blood again or blood pressure change . CONCLUSIONS Although it was not universally effective and the mechanisms of its effects are unclear , AMT is a simple behavioral technique that may be useful in reducing reactions to blood donation The authors compared the safety , efficacy , and effects on gastric volume and pH of oral transmucosal fentanyl citrate ( OTFC ) premedication and of placebo lollipop and no premedication in 55 children undergoing elective operations . The patients were r and omly assigned to receive no premedication ( group A , N = 18 ) ; OTFC containing 15–20 μg/kg of fentanyl citrate ( group B , N = 18 ) ; or a placebo lollipop ( group C , N = 19 ) . Activity ( sedation ) and anxiety scores , vital signs ( including systolic and diastolic arterial blood pressures , heart and respiratory rates ) , and pulse oximetry determined oxygen saturation were measured before and at 10-min intervals after premedication until the patients were taken to the operating room . Gastric contents were aspirated via an orogastric tube and analyzed for volume and pH after induction of anesthesia . Quality of induction and recovery were evaluated using scoring schedules ; recovery times were measured and side effects recorded . OTFC was readily accepted and provided levels of sedation and anxiolysis significantly greater after 10 min than after no premedication or the placebo lollipop . Arterial blood pressures , heart rate , and oxygen saturations were not different among the three groups . In patients given OTFC , respiratory rates were significantly lower after 10 min than they were in patients having no premedication . When compared to patients having no premedication , patients having OTFC had slightly increased gastric volumes ( 14.6 ± 10 vs 7.6 ± 5.3 mL , mean ± SD ) . Patients having a placebo lollipop had similar gastric volumes ( 15.6 ± 13.5 mL ) as those having OTFC . The three groups had similar gastric pH 's ( 1.69 ± 0.31 , 1.92 ± 0.53 and 1.72 ± 0.28 , mean ± SD , groups A , B , and C , respectively ) . Induction and recovery evaluations and recovery times were also similar in the three groups . OTFC was associated with a 50 % incidence of mild , nondisturbing , preoperative facial pruritus and a higher overall incidence of postoperative nausea ( 44 % ) than was premedication with the placebo lollipop ( 16 % ) or no premedication ( 0 % ) . The results demonstrate that OTFC is readily accepted , safe , and more effective than no premedication or premedication with a placebo lollipop , and does not affect gastric pH but does increase gastric volume One hundred twenty patients about to receive their first treatment with potentially nauseant cancer chemotherapy were r and omized to one of six antiemetic treatments : ( 1 ) no treatment ; ( 2 ) placebo ; ( 3 ) prochlorperazine ( PCPZ ) , 10 mg ; ( 4 ) delta 9-tetrahydrocannabinol ( THC ) , 5 mg ; ( 5 ) THC , 10 mg ; ( 6 ) THC , 15 mg . Four doses of each medication were given orally at 4-hour intervals starting 2 hours before chemotherapy . A study nurse was responsible for both objective ( nurse ) and subjective ( patient ) symptom question naires . Serum levels were obtained at intervals for cross-reacting cannabinoids . Physiologic measurements including intraocular pressure ( IOP ) , blood pressure , and pulmonary function were also recorded . In summary , the patients were remarkably free of adverse physiologic effects . All intraocular pressures before and after treatment were within the normal range , although a surprising statistically significant increase in IOP occurred in the group receiving 5 mg THC Abstract Forty-eight moderately intellectually-h and icapped , institutionalized adults were r and omly assigned to a behavioural social-skills training ( BSST ) , a cognitive social-problem-solving ( SPS ) , attention-placebo control ( APC ) or no-treatment control ( NTC ) group . Significant improvement in basic social-skill performance was found for the BSST group but not for the SPS , APC or NTC groups , whereas significant increases in the generation of alternative solutions were found for the cognitive SPS group but not the BSST , APC or NTC groups . Neither training approaches produced lasting benefits , nor were skill improvements associated with changes in global ratings of social competence made by staff . The implication s for future intervention with intellectually-h and icapped adults are discussed A single-blind , r and omized , placebo-controlled study was performed to evaluate auricular acupuncture ( AAc ) in the treatment of cocaine addiction . Two linked but concurrent studies were done . In Study 1 , residential clients ( N = 236 ) were r and omized to true acupuncture ( Ac ) , sham Ac , and conventional treatment without Ac . Treatment group subjects received Ac at three ear points considered to be specific for the treatment of substance abuse ( SA ) . Control subjects received three nonspecific ( sham ) points . In Study 2 , day treatment clients ( N = 202 ) were r and omized to one of three dose levels of true Ac ( 28 , 16 , or 8 treatments ) . Subjects received Ac at five , rather than three , specific ear points . Nonspecific ( sham ) points were not used in Study 2 . With rare exception , the data failed to identify significant treatment differences among the true and sham Ac , and psychosocial groups . Furthermore , no differences were observed among the three dose levels of true Ac This study explores the effect of positive and negative placebo suggestions on pain induced by h and exposures to ice water . Thirty-six participants were r and omly assigned to one of the following interventions : ( a ) positive placebo suggestion , ( b ) negative placebo suggestion , and ( c ) control . The positive placebo-suggestion participants were given favorable messages about the beneficial effects of ice-water h and immersion . The negative placebo-suggestion group was given messages depicting the negative effects of exposure to ice water . The control groups were given neutral messages about exposure to ice water . Participants rehearsed the messages and focused on them during their second h and exposures . Results indicate that both the positive and negative placebo-suggestion interventions significantly altered participants ' pain threshold , pain tolerance , and pain endurance . Participants exposed to a positive placebo condition tolerated pain better than a neutral condition . Participants exposed to a negative placebo did not tolerate pain as well as participants with a neutral condition OBJECTIVE The objectives of the Cost Effectiveness of Lipid Lowering ( CELL ) study were twofold : ( i ) to evaluate the effect on overall cardiovascular risk of two types of health care advice ( " usual ' and " intensive ' ) given in primary care , with or without pharmacological medication , with the target being to attain a moderate decrease in cholesterol ; ( ii ) to evaluate the ritual of daily medication on compliance with the health care advice . DESIGN A prospect i ve , double-blind , r and omized , controlled trial of 18 months ' duration . SETTING The study was carried out in 32 health centres ( out of a total of approximately 850 ) in Sweden . SUBJECTS In all , 681 subjects , aged 30 - 59 years , were r and omized . They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia ( total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL : HDL cholesterol ratio of more than 4.0 ) . Most ( 87 % ) of the subjects were males ; 626 subjects ( 92 % ) completed the 18-month follow-up . INTERVENTION Half the subjects were r and omized to ' intensive advice ' given in group sessions led by doctors and nurses in primary care . The other half received ' usual advice ' . In each of the two advice groups , one-third received an active lipid-lowering drug ( pravastatin ) , one-third placebo , and one-third no drug at all . The tablets were titrated to achieve a 15 % reduction in cholesterol . MAIN OUTCOME MEASURES Changes in the overall Framingham risk score , and the development of adverse events in each group . RESULTS The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication ( together with intensive advice -0.13 ; 95 % CI-0.20 , -0.06 , and together with usual advice -0.16 ; 95 % CI -0.23 , -0.09 ) . The other subjects receiving intensive advice tended to fare better than those on usual advice . Lifestyle was not influenced significantly over the study period . The ritual of daily medication did not affect the outcome . CONCLUSION As expected , lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease . There was no additive effect of intensive advice to these subjects . However , there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs . One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol . There was no benefit from the ritual of taking daily medication A prospect i ve study was design ed to test the efficacy of pressure at the P6 ( Neiguan ) acupuncture point , in preventing morning sickness . Three groups of patients in early pregnancy recorded the severity and frequency of sickness over a period of 4 consecutive days following daily pressure at P6 point , pressure at a point near the right elbow and with no treatment . Troublesome sickness was significantly less in both the genuine ( 23/119 ) and dummy ( 41/112 ) pressure groups as compared with the control series ( 67/119 ) . When the data are adversely ‘ weighted ’ to compensate for the lower incidence of fully completed returns in the active treatment groups , only the P6 group show a significant reduction in sickness . No side effects occurred in either group and while anticipation of benefit may offer a partial explanation for the findings , pressure at the Neiguan point appears to have a specific therapeutic effect Many asthmatic patients are reluctant to follow the medication schedule prescribed for them and turn to alternative treatment methods . The results of this study indicate that one such method , laser acupuncture , does not prevent exercise-induced asthma This study investigated the utility of cognitive retraining procedures in the treatment of schizophrenia . Twenty in- patients were matched on reaction time and assigned to one of three groups : experimental-treatment , attention-placebo and no-treatment control . Subjects participating in the experimental attention-training programme exhibited significantly greater reaction-time improvement than controls . The data suggest that practice on cognitive tasks can improve the attentional performance of chronic schizophrenic patients During a 5-month study , we examined the effects of the relaxation response on premenstrual syndrome in 46 women who were r and omly assigned to one of three groups : a charting group , a reading group , and a relaxation response group . The relaxation response group showed significantly greater improvement than the charting and the reading groups on physical symptoms ( P < .025 for both comparisons ) . There was a significant group-by-severity effect for charting versus relaxation response and for reading versus relaxation response on symptoms measured daily ( P < .01 for both comparisons ) , on emotional symptoms measured retrospectively ( P < .001 and P < .025 , respectively ) , and on symptoms of social withdrawal measured retrospectively ( P < .01 and P < .025 , respectively ) . Women with severe symptoms in the relaxation response group showed a 58.0 % improvement , compared with a 27.2 % improvement for the reading group and a 17.0 % improvement for the charting group . We conclude that regular elicitation of the relaxation response is an effective treatment for physical and emotional premenstrual symptoms , and is most effective in women with severe symptoms . ( Obstet Gynecol 75:649 , 1990 & NA ; Ultrasound ( US ) therapy is used to reduce pain and inflammation and to accelerate healing after soft tissue injury . However , there is little objective evidence of its effectiveness and the mechanisms which may cause these effects are unknown . In a placebo‐controlled double‐blind clinical trial we examined the contribution of placebo and massage effects in ultrasound therapy following bilateral surgical extraction of lower third molars . Four to 6 h after surgery the patients ( 25 per group ) received either no therapy , US ( 0.1 W/cm2 ) , ‘ mock ’ US with massage , ‘ mock ’ US without massage , or ‘ self‐massage ’ with a dummy applicator . Facial swelling , trismus , serum C‐reactive protein , serum cortisol , pain and anxiety were measured 24 h postoperatively . The results showed that the beneficial analgesic and anti‐inflammatory effects of US therapy were placebo‐mediated , with maximum effect in the placebo ( ‘ mock ’ US ) group without circular massaging with the applicator ) . Self‐massage by the patient produced no significant effect . This placebo action was independent of changes in serum cortisol or patient anxiety state . US therapy can significantly reduce postoperative morbidity , but by placebo‐mediated mechanisms which are unrelated to the US itself It has been reported that administration of prophylactic penicillin may prevent flare-ups or other undesirable posttreatment sequelae following root canal treatment . To test this hypothesis in a prospect i ve study , 80 patients with a diagnosis of pulp necrosis and chronic apical periodontitis were divided into three groups : group A ( prophylactic penicillin , AHA recommendation ) , group B ( placebo , same regimen ) , and group C ( no medication ) . Medications and evaluations were double-blinded . Patients reported their posttreatment events including incidence of flare-ups , incidence and severity of pain/swelling , and occurrence of adverse side effects . Differences in the three groups were determined statistically using chi-square tests . The outcome showed no significant difference ( p = 0.68 ) among the three groups . That is , administration/nonadministration of penicillin prophylactically was unrelated to posttreatment signs and symptoms following canal preparation . Incidence of flare-ups was very low ( 1 of 80 ) . Occurrence of pain in the mild-moderate levels was fairly high ( approximately 70 % overall ) , but was primarily in the mild category . Overall incidence of side effects was also very low ( 2 of 80 ) . Severe levels of pain/swelling and flare-up incidence were low with no difference between administration or nonadministration of antibiotics . Based on our data , using penicillin ( a potentially dangerous drug ) prophylactically to control posttreatment symptoms is not recommended in cases of pulp necrosis and asymptomatic periapical pathosis The authors describe a medical center-based r and omized trial aim ed at determining the feasibility and effectiveness of partnering patients and primary -care providers with an exercise health counselor . Study participants included 165 veterans age 70 years and older . The primary end point was change in physical activity at 3 and 6 months comparing patients receiving high-intensity physical activity counseling , attention control counseling , and usual care after receiving st and ardized clinic-based counseling . We noted a significant Group x Time interaction ( p = .041 ) for physical activity frequency and a similar effect for caloric expenditure ( p = .054 ) . Participants receiving high-intensity counseling and usual care increased physical activity over the short term , but those with usual care returned to baseline by the end of the study . The intervention was well received by practitioners and patients . We conclude that partnering primary -care providers with specialized exercise counselors for age- and health-appropriate physical activity counseling is effective & NA ; Although high‐frequency low‐intensity transcutaneous electric nerve stimulation ( TENS ) has been extensively used to relieve low back pain , experimental studies of its effectiveness have yielded contradictory findings mainly due to method ological problems in pain evaluation and placebo control . In the present study , separate visual analog scales ( VAS ) were used to measure the sensory‐discriminative and motivational‐affective components of low back pain . Forty‐two subjects were r and omly assigned to 1 of 3 groups : TENS , placebo‐TENS , and no treatment ( control ) . In order to measure the short‐term effect of TENS , VAS pain ratings were taken before and after each treatment session . Also , to measure long‐term effects , patients rated their pain at home every 2 h throughout a 3‐day period before and 1 week , 3 months and 6 months after the treatment sessions . In comparing the pain evaluations made immediately before and after each treatment session , TENS and placebo‐TENS significantly reduced both the intensity and unpleasantness of chronic low back pain . TENS was significantly more efficient than placebo‐TENS in reducing pain intensity but not pain unpleasantness . TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness . This additive effect was not found for placebo‐TENS . When evaluated at home , pain intensity was significantly reduced more by TENS than placebo‐TENS 1 week after the end of treatment , but not 3 months and 6 months later . At home evaluation of pain unpleasantness in the TENS group was never different from the placebo‐TENS group . These results suggest that TENS reduces both the sensory‐discriminative and motivational‐af‐fective components of low back pain in the short term but that much of the reduction in the affective component may be a placebo effect . We conclude that TENS should be used as a short‐term analgesic procedure in a multidisciplinary program for low back pain rather than as an exclusive or long‐term treatment BACKGROUND Transcutaneous electrical nerve stimulation ( TENS ) has been used extensively to control postoperative pain , but its effects are controversial . This is probably due to the different types of operations performed and , therefore , to the varying intensity of postoperative pain . Here we present an extensive study with TENS in 324 patients who underwent different types of thoracic surgical procedures : posterolateral thoracotomy , muscle-sparing thoracotomy , costotomy , sternotomy , and video-assisted thoracoscopy . METHODS Each patient cohort was r and omly subdivided into three treatment groups : TENS , placebo TENS and control . The effectiveness of TENS was assessed by two factors : the time from the beginning of treatment to the request for further analgesia and the total medication intake during the first 12 hours after operation . RESULTS Whereas posterolateral thoracotomy produced severe pain , muscle-sparing thoracotomy , costotomy , and sternotomy caused moderate pain , and video-assisted thoracoscopy caused only mild pain . The TENS treatment was not effective in the posterolateral thoracotomy group , but it was useful as an adjunct to other medications in the muscle-sparing thoracotomy , costotomy , and sternotomy groups . In contrast , representing the only pain control treatment with no adjunct drugs , it was very effective in patients having video-assisted thoracoscopy . CONCLUSIONS These findings show that TENS is useful after thoracic surgical procedures only when postoperative pain is mild to moderate ; it is uneffective for severe pain Objective To investigate the benefit of adding acupuncture to a course of advice and exercise delivered by physiotherapists for pain reduction in patients with osteoarthritis of the knee . Design Multicentre , r and omised controlled trial . Setting 37 physiotherapy centres accepting primary care patients referred from general practitioners in the Midl and s , United Kingdom . Participants 352 adults aged 50 or more with a clinical diagnosis of knee osteoarthritis . Interventions Advice and exercise ( n=116 ) , advice and exercise plus true acupuncture ( n=117 ) , and advice and exercise plus non-penetrating acupuncture ( n=119 ) . Main outcome measures The primary outcome was change in scores on the Western Ontario and McMaster Universities osteoarthritis index pain subscale at six months . Secondary outcomes included function , pain intensity , and unpleasantness of pain at two weeks , six weeks , six months , and 12 months . Results Follow-up rate at six months was 94 % . The mean ( SD ) baseline pain score was 9.2 ( 3.8 ) . At six months mean reductions in pain were 2.28 ( 3.8 ) for advice and exercise , 2.32 ( 3.6 ) for advice and exercise plus true acupuncture , and 2.53 ( 4.2 ) for advice and exercise plus non-penetrating acupuncture . Mean differences in change scores between advice and exercise alone and each acupuncture group were 0.08 ( 95 % confidence interval −1.0 to 0.9 ) for advice and exercise plus true acupuncture and 0.25 ( −0.8 to 1.3 ) for advice and exercise plus non-penetrating acupuncture . Similar non-significant differences were seen at other follow-up points . Compared with advice and exercise alone there were small , statistically significant improvements in pain intensity and unpleasantness at two and six weeks for true acupuncture and at all follow-up points for non-penetrating acupuncture . Conclusion The addition of acupuncture to a course of advice and exercise for osteoarthritis of the knee delivered by physiotherapists provided no additional improvement in pain scores . Small benefits in pain intensity and unpleasantness were observed in both acupuncture groups , making it unlikely that this was due to acupuncture needling effects . Trial registration Current Controlled Trials IS RCT N88597683 OBJECTIVE To determine the effect of chiropractic care on jet lag in Finnish junior elite athletes . SUBJECTS Fifteen Finnish junior elite athletes . METHODS Through use of a table of r and om numbers , each athlete was assigned by sex to one of 3 groups : chiropractic adjustment , sham adjustment , or control . As needed , the chiropractic adjustment group athletes ( n = 5 ) were adjusted on a daily basis by licensed chiropractors using a toggle/recoil procedure . The sham adjustment group athletes ( n = 5 ) received sham adjustments on a daily basis by licensed chiropractors . The control group athletes ( n = 5 ) were not adjusted or sham-adjusted but participated in all test protocol s. Sleep , jet lag , chiropractic , and mood data ( the last acquired through use of the Profile of Mood States ) were collected on a daily basis for 18 consecutive days . RESULTS Repeated- measures analyses of variance ( 3 x 2 ) of total mood disturbance scores and heart rate variables indicated that there were no significant ( .05 level ) between-group differences . Sleep data were analyzed through use of a 3 x 2 , repeated- measures multivariate analysis of variance . Pillai 's trace indicated that there were no between-group differences . Self- assessment of jet lag by participants after traveling to Georgia and after returning to Finl and showed no between-group differences . CONCLUSIONS It was concluded that chiropractic care did not reduce the effects of jet lag Sixty-six chronic low back pain sufferers were r and omly divided into three groups . Following individual assessment s consisting of psychological question naires , pain monitoring , and measurement of paraspinal electromyogram ( EMG ) , one group received paraspinal EMG biofeedback and another a placebo treatment . The third group received no intervention . Two further assessment s were carried out on all groups immediately after treatment and at a 3-month follow-up . All groups showed significant reduction in pain , anxiety , depression , and paraspinal EMG following treatment and at follow-up , but there were no differences between groups . A regression analysis failed to identify subjects ' characteristics that predicted positive outcome in the biofeedback group . However , high scores on the Evaluative scale of the McGill Pain Question naire and high hypnotizability were significant predictors of positive outcome for the placebo group . It is concluded that paraspinal EMG biofeedback is not a specific treatment for chronic low back pain in a nonhospitalized population Two experiments ( N=56 ) investigated the relationship between subjects ’ expectancies concerning the effect of caffeine on a motor skill , and the type of placebo response . Male subjects were assigned to four groups . Three groups expected to receive caffeine but received a placebo . Prior to the placebo , two of the groups received information about the effect of caffeine on a motor skill task which led one group E(+ ) to expect enhanced performance , and the other E(− ) to expect impairment . The third placebo group received no information E ( ? ) . A control group E(0 ) received no beverage , so neither caffeine nor any effect on performance was expected . The expected type of effect predicted the type of placebo response displayed . Group E(+ ) displayed greater improvement under placebo than did group E(0 ) , and group E(− ) performed more poorly than those in group E(0 ) . No placebo response was observed in group E ( ? ) . Placebo effects on mood were correlated with subjects ’ predictions about the effect of caffeine on mood . The role of expectancies in response to placebos and psychoactive drugs is discussed The efficacy of transcutaneous electrical nerve stimulation ( TENS ) as an adjunct to narcotic medications for the management of postoperative pain was assessed in a prospect i ve , r and omized , controlled study of patients following coronary artery bypass graft ( CABG ) surgery with the right or left internal thoracic artery ( ITA ) . Forty-five male patients ( mean age , 57 + /- 6 years ) were r and omly assigned to ( 1 ) TENS , ( 2 ) placebo TENS , or ( 3 ) control treatments ( n = 15 each ) , following extubation and during the 24- to 72-h postoperative period . Two-way analysis of variance tests indicated no significant differences among treatment groups for ( 1 ) pain with cough , ( 2 ) narcotic medication intake , ( 3 ) FVC , ( 4 ) FEV1 , and ( 5 ) PEFR ( p > 0.05 ) . However , pain at rest reported by the TENS group was significantly lower than that reported by the control group ( treatment main effect ; p < 0.04 ) , although no significant differences were observed between the TENS and placebo or between the placebo and control groups ( p > 0.05 ) . All six criterion measures were characterized by significant changes over time for the entire group ( n = 45 ; time main effect ; p < 0.01 ) , as follows : pain and medication intake were similar on days 1 and 2 , but were significantly less on day 3 , and pulmonary functions were significantly lower than preoperatively on day 1 , decreased further on day 2 , and despite an improvement on day 3 , remained significantly lower than preoperative values ( p < 0.01 ) . This study suggests that the addition of TENS , applied continuously during the immediate postoperative period following CABG with ITA , may not be advantageous in pain management or the prevention of pulmonary dysfunction One-hundred-sixteen patients suffering from vascular headache ( migraine or combined migraine and tension ) were , after 4 weeks of pretreatment baseline headache monitoring , r and omly assigned to one of four conditions : ( a ) thermal biofeedback with adjunctive relaxation training ( TBF ) ; ( b ) TBF plus cognitive therapy ; ( c ) pseudomediation as an ostensible attention-placebo control ; or ( d ) headache monitoring . The first three groups received 16 individual sessions over 8 weeks , while the fourth group continued to monitor headaches . All groups then monitored headaches for a 4-week posttreatment baseline . Analyses revealed that all treated groups improved significantly more than the headache monitoring group with no significant differences among the three treated groups . On a measure of clinical ly significant improvement , the two TBF groups had slightly higher ( 51 % ) degree of improvement than the meditation group ( 37.5 % ) . It is argued that the attention-placebo control became an active relaxation condition A r and omized controlled trial was used to evaluate the effectiveness of relaxation training in the treatment of paediatric migraine . Relaxation training was compared with-two control groups ( psychological placebo and ' own best efforts ' ) in a total of 99 children and adolescents with frequent migraine . Daily recording of the headaches following treatment , three months after treatment and at the one-year follow-up indicated that all three treatments were equally effective . The importance of the use of adequate control conditions which generate equivalent expectancies in pain treatment research was confirmed This study examined the effects of chiropractic adjustments of the thoracic spine ( T1-T5 ) on blood pressure and state anxiety in 21 patients with elevated blood pressure . Subjects were r and omly assigned to one of three treatment conditions : active treatment , placebo treatment , or no treatment control . The adjustments were performed by a mechanical chiropractic adjusting device . Dependent measures obtained pre- and post-treatment included systolic and diastolic blood pressure , and state anxiety . Results indicated that systolic and diastolic blood pressure decreased significantly in the active treatment condition , whereas no significant changes occurred in the placebo and control conditions . State anxiety significantly decreased in the active and control conditions . Results provide support for the hypothesis that blood pressure is reduced following chiropractic treatment . Further study is needed to examine the long-term effects of chiropractic treatment on blood pressure After conducting a r and omized , 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy , we asked those individuals who survived the 3-year trial receiving active medication ( with or without psychotherapy ) to continue in a 2-year additional r and omized trial of active medication vs placebo . The question was whether maintaining antidepressant medication at the dosage used to treat the acute episode beyond 3 years would continue to provide a significant prophylactic effect compared with medication discontinuation after the 3 years of effective maintenance treatment . Survival analysis demonstrated a highly significant continued prophylactic effect for active imipramine hydrochloride treatment maintained at an average dose of 200 mg . We conclude that active imipramine treatment is an effective means of preventing recurrence beyond 3 years and that patients with previous episodes less than 2 1/2 years apart , therefore , merit continued prophylaxis for at least 5 years & NA ; Sensitivity to painful thermal stimuli and willingness to report pain were studied in two experimental sessions . No treatment was given during the first session , but on the second session a placebo was administered as a potent , fast‐acting analgesic . The placebo failed to affect sensitivity to thermal stimulation , but significant decreases in willingness to report pain were observed . A side effects question naire showed that a significant number of side effects were reported by subjects on the placebo session BACKGROUND AND OBJECTIVE This study investigates ( 1 ) whether treatment by homeopaths is more efficacious than self-selected conventional health care and ( 2 ) whether self-treatment with self-selected homeopathic medicines is more efficacious than placebo in preventing childhood upper respiratory tract infections ( URTIs ) . DESIGN A four-arm r and omized controlled trial involving two independent investigations , one open and pragmatic ( evaluating the effect of treatment by homeopaths including homeopathic medicines ) and one double-blinded ( evaluating the effect of self-treatment with homeopathic medicine ) . PATIENTS The planned sample size is 420 children below the age of 10 , recruited by a postal invitation to all children diagnosed with URTIs when attending a casualty department in Trondheim , Norway . INTERVENTIONS The children are r and omly assigned to receive either ( 1 ) self-selected homeopathic medicine or placebo ( 270 patients ) , ( 2 ) treatment by one of four different homeopaths who could prescribe any homeopathic medicine ( 75 patients ) , or ( 3 ) waiting list control using self-selected conventional health care ( 75 patients ) . MAIN OUTCOME MEASURE Total URTI symptom scores from patients ' diary over 12 weeks . PLAN : The results of these two studies ( available at the end of 2004 ) have the potential to provide information about the efficacy of treatment by homeopaths independently from the efficacy of homeopathic medicines in children with URTIs A prospect i ve , controlled , double-blinded investigation was conducted to evaluate whether infants undergoing circumcisions with 1 % lidocaine dorsal penile nerve blocks experienced decreased stress as compared with those receiving saline solution injections or no injections . Stress was measured in terms of pulse rate and oxygen saturation on a pulse oximeter . A subjective grading scale was also developed to measure infant irritability . The total number in the study was 51 with 23 infants in the lidocaine group , 21 in the saline solution group , and 7 in the no injection group . The results of the study revealed an average increase of 28.8 % in the pulse rate above baseline for the control infants ( p less than 0.001 ) versus no significant change in the lidocaine group . The average oxygen saturation of the control groups decreased by 5.6 % from baseline ( p less than 0.001 ) , and that of the lidocaine group decreased by 1.0 % , which was not a significant change . The subjective data were gained by using a grading scale of 1 to 6 with 1 being the least irritable infant and 6 being the most irritable infant . The physician evaluation gave an average rating of 4.2 to the control group versus 2.4 for the lidocaine group ( p less than 0.001 ) . The nursing evaluation during the procedure gave an average rating of 4.2 to the control group versus 2.3 to the anesthetized group ( p less than 0.001 ) . The subjective evaluation of infants before and after the procedure was not significantly different . There were no major complications in any of the groups OBJECTIVE To quantitate pain relief associated with paracervical local anesthesia during transvaginal ultrasound-guided collection . DESIGN The study was a prospect i ve , r and omized , double-blinded , placebo-controlled , and no treatment-controlled investigation . Pain scores for vaginal pain associated with entry into the cul-de-sac and global assessment for the entire procedure were generated separately by patient and physician . Variables evaluated include duration of procedure , patient weight and age , total number of vaginal and ovarian " follicular " punctures , number of oocytes retrieved , and amount of IV medication . SETTING A private IVF-ET program . PATIENTS Women in an IVF-ET program who volunteered to join the study ( n = 101 ) . INTERVENTIONS Local anesthesia as a paracervical block compared with placebo or no injection during transvaginal oocyte retrieval , with all patients receiving IV sedation . RESULTS Both vaginal and global pain scores , whether patient or physician assessed were lower for paracervical block than placebo . Agreements between physician and patient assessment s of pain scores were close . Duration of the procedure was correlated with pain score . In general , a placebo effect on pain perception compared with no injection was not seen . CONCLUSION Paracervical local anesthesia compared with placebo injection was associated with lower pain scores for both vaginal puncture and global assessment of the oocyte retrieval process but was not significantly better than no injection for global evaluation The specific aim of this study was to investigate the efficacy of elicitation of the relaxation response for the treatment of menopausal hot flashes and concurrent psychological symptoms . The volunteer sample consisted of 33 women , between the ages of 44 and 66 years , who were in general good health , with a minimum of 6 months without a menstrual period , experiencing at least five hot flashes per 24-h , and not using hormone replacement therapy . The setting was an outpatient clinic in a tertiary care teaching hospital . The interventions used were relaxation response training and an attention-control group and a daily symptom diary measuring both the frequency and intensity of hot flashes , the Spielberger State-Trait Anxiety Inventory ( STAI ) , and the Profile of Mood Scale ( POMS ) were the measures used . This was a r and omized , controlled , prospect i ve study . Subjects were r and omly assigned to one of three groups ( relaxation response , reading , or control ) for the 10-week study . The first 3 weeks of baseline measurement of frequency and intensity of hot flash symptoms , and the preintervention psychological scores were compared with the final 3 weeks measurement of frequency and intensity and the postintervention psychological scores for symptomatic improvement . The relaxation response group demonstrated significant reductions in hot flash intensity ( p < 0.05 ) , tension-anxiety ( p < 0.05 ) and depression ( p < 0.05 ) . The reading group demonstrated significant reductions in trait-anxiety ( p < 0.05 ) and confusion-bewilderment ( p < 0.05 ) . There were no significant changes for the control group . Daily elicitation of the relaxation response leads to significant reductions in hot flash intensity and the concurrent psychological symptoms of tension-anxiety and depression Abstract The effectiveness of a package treatment for reducing nailbiting was studied . The package was composed of both positive procedures aim ed at teaching adaptive behavior to substitute for nailbiting and negative procedures aim ed at advancing skills for suppressing nailbiting . The design of the study permitted an analysis of the contributions of both positive and negative components of the package . Subjects assigned to combined , positive , negative and placebo groups received four weekly treatment sessions , and changes in their nailbiting behavior were compared with untreated controls . As in previous studies , nonspecific factors such as dem and and attention to ones nails were found to be important determinants of outcome . In addition , positive procedures were found to be substantially more important than negative procedures in the maintenance of reductions in nailbiting over a 4-month follow-up period CONTEXT Although the traditional treatment of headache has been pharmacological , there have been many attempts to treat headaches with other methods with mixed levels of success . OBJECTIVE To obtain preliminary data on the efficacy of the Trager approach in the treatment of chronic headache . DESIGN Small-scale r and omized controlled clinical trial . SETTING University-based clinic . PATIENTS Thirty-three volunteers with a self-reported history of chronic headache with at least one headache per week for at least 6 months . INTERVENTIONS Medication only control group , medication and attention control group , and medication and Trager treatment group . MAIN OUTCOME MEASURES Self-reported frequency , duration , and intensity of headache , medication usage and headache quality of life ( HQOL ) obtained at baseline and after a 6-week treatment period . RESULTS Analyses of variance demonstrated significant improvement in HQOL for the Trager and attention control groups , and reduction in medication usage for the Trager group ( P < 0.05 ) . Within-group analyses revealed that participants r and omized to Trager demonstrated a significant decrease in the frequency of headaches ( P = 0.045 ) , improvement in HQOL ( P = 0.045 ) , and a 44 % decrease in medication usage ( P = 0.03 ) . Participants r and omized to the attention control group demonstrated a significant improvement in HQOL ( P = 0.035 ) and a 19 % decrease in medication usage ( P = 0.15 ) . Participants r and omized to the no-treatment control group revealed a significant increase in headache duration ( P = 0.025 ) and intensity ( P = 0.025 ) , and a declination in HQOL ( P = 0.035 ) . CONCLUSIONS The Trager approach decreased headache frequency and medication usage . Trager and physician attention improved HQOL . A larger , multi-site study is recommended Twenty of sixty volunteers for smoking cessation were assigned to single-session hypnosis , 20 to a placebo control condition , and 20 to a no-treatment control condition . The single-session hypnosis group smoked significantly less cigarettes and were significantly more abstinent than a placebo control group and a no treatment control group at posttest , and 4-week , 12-week , 24-week and 48-week follow-ups Abstract A class experiment for medical students Summary was devised to demonstrate the influence of the placebo effect and non-drug factors on response to drugs . The subjects were conditioned to expect sedative or stimulant effects , but all received placebo in one or two blue or pink capsules . Predictions about the size and nature of the placebo response and influence of the non-drug factors were made before the experiment and discussed afterwards . Four of six predictions were fully confirmed . Drug- associated changes were reported by 30 % of the subjects and were severe in 1 or 2 individuals . Two capsules produced more noticeable changes than one , and blue capsules were associated with more sedative effects than pink capsules . Students rated the experiment highly both as a learning experience and for its relevance to their future practice of medicine Abstract Five hundred and fifty-eight cigarette smokers ( mean 31 cigarettes/day ) were r and omized in four groups : Acupuncture , Behaviour Therapy , Placebo Medication and Waiting-list Control . The life-table analysis of smoking cessation showed , at a 12-month follow-up , no difference between Acupuncture , Behaviour Therapy and Placebo . Differences appeared only in an analysis of the abstinent subjects at each data point . Behaviour Therapy and Acupuncture accounted for significantly more abstinent subjects than Placebo at the end of the 2-week therapeutic phase . However at 9 and 12 months Acupuncture had a statistically-significant greater number of abstinent subjects than Behaviour Therapy , but there was no difference between Acupuncture and Placebo . The percentage decrease in smoking from baseline appeared significantly greater at 12 months in the first three groups than in the Control conditions . However , as in most smoking-cessation studies , the overall effect was small and non-specific . The results reflect the importance of maintenance programmes and of the prevention of addiction OBJECTIVE The authors examined the effectiveness of unguided self-help as a first step in the treatment of bulimia nervosa . METHOD A total of 85 women with bulimia nervosa who were on a waiting list for treatment at a hospital-based clinic participated . The patients were r and omly assigned to receive one of two self-help manuals or to a waiting list control condition for 8 weeks . One of the self-help manuals addressed the specific symptoms of bulimia nervosa ( cognitive behavior self-help ) , while the other focused on self-assertion skills ( nonspecific self-help ) . RESULTS Twenty patients ( 23.5 % ) dropped out of the study . The data were analyzed with intention-to-treat analysis . Although the group-by-time interaction for binge eating and purging was not statistically significant , simple effects showed that there was a significant reduction in symptom frequency in both self-help conditions at posttreatment but not in the waiting list condition . There were no statistically significant changes in levels of dietary restraint , eating concerns , concerns about shape and weight , or general psychopathology . A greater proportion of patients in the cognitive behavior self-help ( 53.6 % ) and nonspecific self-help ( 50.0 % ) conditions reported at least a 50 % reduction in binge eating or purging at posttreatment , compared with the waiting list condition ( 31.0 % ) . A lower baseline knowledge about eating disorders , more problems with intimacy , and higher compulsivity scores predicted a better response . CONCLUSIONS The findings suggest that a subgroup of patients with bulimia nervosa may benefit from unguided self-help as a first step in their treatment . Cognitive behavior self-help and nonspecific self-help had equivalent effects & NA ; Although in most of the cases the placebo response appears to be unpredictable , several factors have been considered in order to explain the placebo analgesic effect . For example , it is widely recognized , albeit with little empirical evidence , that placebo analgesia is more likely to occur after a successful analgesic therapy . On the basis of this assumption , we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain . However , due to the high variability of opioid responsiveness , buprenorphine was effective in some patients and poorly effective in some others . Similarly , buprenorphine produced respiratory depression with a large variability , ranging from mild depression to no effect . We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day . Analogously , we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before , irrespective of the analgesic effectiveness . These specific effects suggest that ( 1 ) the placebo effect is experience‐dependent ; ( 2 ) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and , by considering the role of endogenous opioids in placebo analgesia , might involve different sub population s of opioid receptors The purpose of this study was to evaluate pain scores and plasma beta-endorphin levels following a single spinal adjustive manipulation in subjects with acute low back pain . Eighteen subjects were r and omly assigned to either a control group , which received no treatment ; a sham group , which received only light physical contact ( touch ) ; or an experimental group , which received an adjustive manipulation at a specific lumbar segment . Following a st and ard protocol , all subjects were administered visual analog pain scales and venous blood was drawn 5 min prior to , 5 min after , and 30 min after intervention . Analysis of the pain scores indicated that there was a slight , but significant , reduction of pain in the experimental group , but no similar reduction in the control or sham groups . Furthermore , this reduction of pain in the experimental group was not accompanied any significant change in the plasma beta-endorphin concentration Several medical areas that require patient compliance have successfully used psychological interventions emphasizing cognitive behavioral components . However , there are no published reports on the effect of cognitive behavioral interventions on oral hygiene in adults using an experimental design . For this study , 100 male veterans age 21 - 65 years were r and omly assigned to 4 groups ( cognitive behavioral , education , attention control , and control ) ; to compare the effectiveness of these interventions on oral hygiene , a 5-week pre-test-post-test design was utilized . The dependent variables were self-report of brushing and flossing behavior and dental plaque levels utilizing the plaque index . After the interventions , there was only one significant difference between the control and the experimental groups for brushing frequency . There were no significant differences among the experimental groups for this intervention . The self-report of flossing frequency significantly increased in all 3 treatment groups , but there were no significant differences between these groups . In addition , plaque levels decreased significantly in all 3 experimental groups . Plaque levels in the cognitive behavioral group were significantly lower than those of the educational group . It was not possible to determine whether the greater plaque reduction in the cognitive-behavioral group could be attributed to the nature of the intervention or to the extra time spent with patients in the cognitive behavioral group OBJECTIVE We carried out a prospect i ve , r and omized study to evaluate the usefulness of premedication with an oral anticholinergic for relief of pain during and after a barium enema of the colon . SUBJECTS AND METHODS Patients were r and omized into three groups : no medication , placebo , and sublingual 1-hyoscyamine sulfate . The placebo or hyoscyamine tablet was placed under the tongue 15 - 30 min before the examination . After the procedure the patients were interviewed . An analog scale ( 0 - 10 ) was used to score the level of pain that the patients experienced during the examination . Forty-eight hours after the examination , the patients returned by mail a survey that used the same scale and asked about delayed pain . RESULTS Data from 110 patients were studied . Sixty-nine patients were women , and 41 were men . They ranged from 24 to 82 years old ( mean , 55 years ) . For the no-medication group ( n = 36 ) , the mean pain score was 4.1 ; for the placebo group ( n = 34 ) , 3.8 ; and for the hyoscyamine group ( n = 40 ) , 4.2 . No statistically significant difference in pain scores was found between any groups ( p = .72 ) . Six patients from each group reported minor side effects . The mean scores from the returned surveys ( n = 79 ) were 3.8 for the no-medication group ( n = 26 ) and placebo group ( n = 22 ) and 3.1 for the hyoscyamine group ( n = 31 ) . No statistically significant difference was found between any of these groups ( p = .48 ) or between delayed pain responses and initial pain responses ( p = .27 ) . CONCLUSION Although safe , hyoscyamine seems to provide no benefit over no drug or a placebo when used as a pain premedication for patients undergoing a barium enema & NA ; This prospect i ve , r and omised controlled trial , with three parallel groups , patient and observer blinded for verum and sham acupuncture and a follow up of 3 months raises the question : “ Does a combination of acupuncture and conservative orthopedic treatment improve conservative orthopedic treatment in chronic low back pain ( LBP ) . 186 in‐ patients of a LBP rehabilitation center with a history of LBP ≥6 weeks , VAS ≥50 mm , and no pending compensation cl aims , were selected ; for the three r and om group 4 weeks of treatment was applied . 174 patients met the protocol criteria and reported after treatment , 124 reported after 3 months follow up . Patients were assorted 4 strata : chronic LBP , ≤0.5 years , 0.5–2 years , 2–5 years , ≥5 years . Analysis was by intention to treat . Group 1 ( Verum+COT ) recieved 12 treatments of verum acupuncture and conservative orthopedic treatment ( COT ) . Group 2 ( Sham+COT ) recieved 12 treatments of non‐specific needling and COT . Group 3 ( nil+COT ) recieved COT alone . Verum‐ and Sham acupuncture were blinded against patient and examiner . The primary endpoints were pain reduction ≥50 % on VAS 3 months after the end of the treatment protocol . Secondary endpoints were pain reduction ≥50 % on VAS and treatment efficacy on a four‐point box scale directly after the end of the treatment protocol and treatment efficacy after 3 months . In the whole sample a pain relief of ≥50 % on VAS was reported directly after the end of treatment protocol : Verum+COT 65 % ( 95%CI 51–77 % ) , Sham+COT 34 % ( 95%ci 22–49 % ) , nil+COT 43 % ( 95%ci 29–58 % ) – results are significant for Verum+COT over Sham+COT ( P≤0.02 ) . The results after 3 months are : Verum+COT 77 % ( 95%ci 62–88 % ) , Sham+COT 29 % ( 95%ci 16–46 % ) , nil+Cot 14 % ( 95%ci 4–30 % ) – effects are significant for Verum+COT over Sham+COT ( P≤0.001 ) and for Verum+COT over nil+COT ( P<0.001 ) . No difference was found in the mobility of the patients nor in the intake of NSAID diclofenac . Our conclusion is that acupuncture can be an important supplement of conservative orthopedic treatment in the management of chronic LBP OBJECTIVE To assess the efficacy of acupuncture as an intervention for major depressive disorder ( MDD ) . METHOD Acupuncture was examined in 151 patients with MDD ( DSM-IV ) who were r and omly assigned to 1 of 3 groups in a double-blind r and omized controlled trial . The specific intervention involved Traditional Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression ; the control conditions consisted of ( 1 ) a nonspecific intervention using a comparable number of legitimate acupuncture points not specifically targeted to depressive symptoms and ( 2 ) a waitlist condition , which involved waiting without intervention for 8 weeks . After 8 weeks , all patients received the depression-specific acupuncture . Each 8-week intervention regimen consisted of 12 acupuncture sessions delivered in an acupuncturist 's office in the community . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression . The study was conducted from February 1998 to April 2002 . RESULTS Twenty patients terminated treatment before the completion of the 8-week intervention ( 13 % ) but not differentially by study group . R and om regression models of the intent-to-treat sample revealed that although patients receiving acupuncture improved more than those awaiting intervention , no evidence of differential efficacy of the depression-specific over nonspecific intervention was found . Response rates in acupuncture-treated patients were relatively low after 8 weeks ( 22 % and 39 % for specific and nonspecific intervention groups , respectively ) , with the response rate after the entire 16-week trial reaching 50 % . CONCLUSION Although TCM manual acupuncture is a well-tolerated intervention , results fail to support its efficacy as a monotherapy for MDD . It ca n't be ruled out that factors unique to the implementation of acupuncture in this research study may have limited the efficacy of interventions compared to those provided in naturalistic setting s. CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00010517 PURPOSE / OBJECTIVES To compare differences in the chemotherapy-induced nausea and vomiting ( CINV ) among three groups of women ( acupressure , placebo acupressure , and usual care ) undergoing chemo-therapy for breast cancer . DESIGN A multicenter , longitudinal , r and omized clinical trial throughout one cycle of chemotherapy . SETTING Ten community clinical oncology programs associated with the M.D. And erson Cancer Center and nine independent sites located throughout the United States . SAMPLE 160 women who were beginning their second or third cycle of chemotherapy for breast cancer treatment and had moderate nausea intensity scores with their previous cycles . METHODS Subjects were r and omized to one of three groups : acupressure to P6 point ( active ) , acupressure to SI3 point ( placebo ) , or usual care only . Subjects in the acupressure group were taught to apply an acupressure wrist device by research assistants who were unaware of the active acupressure point . All subjects completed a daily log for 21 days containing measures of nausea and vomiting and recording methods ( including antiemetics and acupressure ) used to control these symptoms . MAIN RESEARCH VARIABLES Acute and delayed nausea and vomiting . RESULTS No significant differences existed in the demographic , disease , or treatment variables among the treatment groups . No significant differences were found in acute nausea or emesis by treatment group . With delayed nausea and vomiting , the acupressure group had a statistically significant reduction in the amount of vomiting and the intensity of nausea over time when compared with the placebo and usual-care groups . No significant differences were found between the placebo and usual-care groups in delayed nausea or vomiting . CONCLUSIONS Acupressure at the P6 point is a value-added technique in addition to pharmaceutical management for women undergoing treatment for breast cancer to reduce the amount and intensity of delayed CINV . IMPLICATION S FOR NURSING Acupressure is a safe and effective tool for managing delayed CINV and should be offered to women undergoing chemotherapy for breast cancer This study compared the effectiveness of progressive relaxation training with and without a supplementary relaxation recording , which the subjects played at home , and an attention placebo manipulation in the modification of severe insomnia in adult volunteers . The results indicated that the relaxation training procedures were significantly more effective than placebo and no-treatment controls in modifying several parameters of sleeping behavior , in reducing consumption of sleep-inducing medication , and in influencing a self-report anxiety measure . The supplementary relaxation tape did not increase the effectiveness of relaxation training conducted in the clinic , and there was no difference in the efficacy of the placebo and no-treatment conditions . Physiological data gathered during the last treatment session indicated few significant correlations between reductions in arousal associated with relaxation training and treatment outcome . Recent years have witnessed increasing interest in the treatment of insomnia from a behavioral framework . Case studies and uncontrolled group investigations suggesting the effectiveness of relaxation training techniques and stimulus control procedures ( Bootzin , 1972 ; Geer & Katkin , 1966 ; Jacobson , 1964 ; Kahn , Baker , & Weiss , 1968 ) have given rise to controlled studies . Thus far this research has indicated that relaxation training procedures are effective in modifying several parameters of sleeping behavior in volunteer insomniacs . However , the mechanism(s ) by which this training operates have not been clearly identified . One possibility is that this technique works because of its placebo value . Relaxation training would seem to have high face validity for the treatment of insomnia , and the impressive proprioceptive muscle feedback often associated with the technique may add to its credibility , Although a number of studies have attempted to investigate this issue ( Borkovec & Fowles , 1973 ; Borkovec , Kaloupek , & Slama , 197S ; Borkovec , Steinmark , & Nan , 1973 ; Haynes , Woodward , Moron , & A sample of physician-referred chronic insomniacs was r and omly allocated to either progressive relaxation , stimulus control , paradoxical intention , placebo or no treatment conditions . Treatment process and outcome were investigated in terms of mean and st and ard deviation ( night to night variability ) measures of sleep pattern and sleep quality . Only active treatments were associated with significant improvement , but the nature of treatment gains varied . In particular , stimulus control improved sleep pattern , whereas relaxation affected perception of sleep quality . All improvements were maintained at 17 month follow-up . Results are discussed with reference to previous research and guidelines are given for clinical practice The objective of this research was to determine the efficacy of enhanced continuity of care and desipramine in increasing treatment attendance and abstinence from cocaine in primary cocaine abusers . Study design was a r and om assignment , placebo-controlled factorial with assessment s at baseline and at 3 ( first week of outpatient treatment ) , 8 , and 12 weeks after start of study . Desipramine blood levels were taken at weeks 2 ( inpatient ) , 3 , and 8 . Subjects ( N = 94 men ) were recruited on an inpatient ward and assigned to increased continuity of care or to st and ard treatment , and to active or placebo drug . Main outcome variables were toxicology-verified reports of cocaine use , and attendance at counseling sessions . Enhanced continuity of care increased abstinence from cocaine at week 3 and increased attendance at individual counseling sessions throughout the 12 weeks of the study . There were no main effects for desipramine . Blood levels above 123 ng/ml at week 2 predicted longer stays in outpatient . We conclude that enhanced continuity of care is a low cost intervention that improves early treatment outcome and attendance ; desipramine effects do not warrant its therapeutic use The effects of maintenance treatment on social adjustment are examined in depressed out patients r and omly assigned to eight months of amitriptyline hydrochloride , a placebo , or no pill , with or without psychotherapy , using a 2 × 3 factorial design . Results for the 106 patients who completed the trial show a significant main effect for psychotherapy apparent only after six to eight months ' treatment . Psychotherapy improved overall adjustment , work performance , and communication , and reduced friction and anxious rumination . There was no effect on the patients ' social adjustment for amitriptyline and there were no drug/psychotherapy interactions . The results support the value of weekly maintenance psychotherapy in recovering depressives . Since amitriptyline has been shown to reduce relapse and prevent symptom return , and psychotherapy was shown to enhance adjustment , there is evidence for combined treatments Objective : The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection ( URTI ) . Methods : Patients with dry or slightly productive cough associated with a history of URTI were recruited . Cough frequency ( CF ) over 15 minutes was recorded by means of a microphone connected to a pen recorder . Cough suppression time ( CST ) was recorded when patients were instructed by means of a red light to try not to cough . Patients received either a single dose of vitamin E ( placebo treatment ) or no treatment . CF and CST were recorded before and 15 minutes after treatment . Results : Twenty-seven patients were r and omized to placebo treatment and 27 to the no-treatment group ( mean age 22.6 years ) . The median difference between post- and pretreatment CF was −3 in the no-treatment group and −18 in the placebo group ( p = .0003 ) . There was a significant increase in CST in the placebo group compared with no treatment ( p = .027 ) . Conclusions : The results demonstrate that placebo treatment has significant antitussive activity . This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids . CF = cough frequency ; CST = cough suppression time BACKGROUND A preliminary report has been interpreted to suggest that gum chewing reduces duration of postcolectomy ileus . STUDY DESIGN We rigorously tested this hypothesis in a prospect i ve , r and omized , placebo-controlled study . Patients undergoing open colectomy ( n = 66 ) were r and omized to receive 1 of 3 postoperative regimens beginning on postoperative day 1 : sips ( control , n = 21 ) ; sips and accupressure wrist bracelet ( placebo , n = 23 ) ; and sips and gum chewing ( treatment , n = 22 ) . Patients were unaware of which regimen constituted placebo or treatment ; end points were assessed by blinded investigators . Power was set a priori at 85 % to detect a 0.75-day difference in time to first postoperative passage of flatus between placebo and treatment groups . Groups were compared using the log-rank test . RESULTS Groups were equivalent with respect to demographic and surgical characteristics . Median times to first postoperative passage of flatus were as follows : sips , 67 hours ; bracelet and sips , 72 hours ; gum and sips , 60 hours ( p = 0.384 ) . There were no significant differences in time to passage of first bowel movement , time until patients were ready for discharge , or time until actual discharge among the three groups . Inpatient and 30-day followup demonstrated no difference in frequency or distribution of postoperative complications . CONCLUSIONS In contrast to findings of a preliminary study , our clinical trial suggests that gum chewing , although safe , does not reduce duration of postcolectomy ileus Goals In a prospect i ve , double-blind study , we examined the effects of routine sedation and pharyngeal anesthesia on cardiorespiratory parameters during gastroscopy . Background Intravenous sedation and topical pharyngeal anesthesia are used to alleviate the discomfort during upper gastrointestinal endoscopy . Cardiorespiratory changes during gastroscopy are common . Study Two hundred fifty two consecutive out patients undergoing gastroscopy were assigned into 4 groups : ( 1 ) sedation with intravenous midazolam and placebo throat spray ( midazolam group ) , ( 2 ) placebo sedation and pharyngeal anesthesia with lidocaine throat spray ( lidocaine group ) , ( 3 ) placebo sedation and placebo throat spray ( placebo group ) , and ( 4 ) no intravenous cannula nor throat spray ( control group ) . Arterial oxygen saturation ( SaO2 ) , systolic and diastolic blood pressure and continuous electrocardiogram were recorded before , during , and after the endoscopic procedure . Results Gastroscopy increased heart rate in all study groups . Premedication with intravenous midazolam or lidocaine spray alleviated this rise ( P<0.001 , repeated measures analysis of variance ) and decreased the incidence of tachycardia . Similarly , sedation with midazolam or topical pharyngeal anesthesia decreased the rise in systolic blood pressure ( P<0.001 ) . Midazolam produced lower SaO2 values during gastroscopy compared with lidocaine , placebo or control groups ( P<0.001 ) . However , episodes of desaturation ( SaO2 ≤92 ) were no more common in the midazolam group than in other groups . Conclusions Premedication with midazolam alleviated the rise in heart rate and systolic blood pressure but induced a statistically significant decrease in arterial oxygen saturation . However , gastroscopy proved to be a safe procedure both with and without sedation OBJECTIVE To evaluate the effect of acupuncture in the prevention of recurrent lower urinary tract infection ( UTI ) in adult women . DESIGN A controlled clinical trial with three arms : an acupuncture group , a sham-acupuncture group , and an untreated control group . Patients were followed for 6 months . SETTING An acupuncture clinic in Bergen , Norway . SUBJECTS Sixty-seven adult women with a history of recurrent lower UTI . MAIN OUTCOME MEASURES Acute lower UTIs during the 6-month observation period . RESULTS Eighty-five percent were free of lower UTI during the 6-month observation period in the acupuncture group , compared with 58 % in the sham group ( p < 0.05 ) , and 36 % in the control group ( p < 0.01 ) . There were half as many episodes of lower UTI per person-half-year in the acupuncture group as in the sham group , and a third as many as in the control group ( p < 0.05 ) . CONCLUSION Acupuncture seems a worthwhile alternative in the prevention of recurring lower UTI in women We investigated the effect of house dust mite (HDM)-allergen avoidance on the development of respiratory symptoms , atopic dermatitis , and atopic sensitization by performing a double blind , placebo-controlled trial . In total , 1,282 allergic pregnant women were selected ( 416 received HDM allergen-impermeable mattress covers for the parents ' and child 's mattress in the third trimester of pregnancy [ active ] , 394 received placebo covers , 472 received no intervention ) . Data on allergen exposure , clinical symptoms , and immunoglobulin E were collected prospect ively . The prevalence of night cough without a cold in the second year of life was lower in the group with active covers compared with the group with placebo covers ( adjusted odds ratio 0.65 ; 95 % confidence interval 0.4 - 1.0 ) . No effect of the intervention was seen on other respiratory symptoms , atopic dermatitis , and total and specific immunoglobulin E. It can be concluded that application of HDM-impermeable mattress covers on the child 's and parents ' beds reduced night cough , but not other respiratory symptoms , atopic dermatitis , and atopic sensitization in the first 2 years of life . Follow-up will determine the long-term effect of the intervention on the development of atopic disease OBJECTIVES To evaluate the efficacy of transcutaneous electrical nerve stimulation ( TENS ) for its effectiveness in eliminating or minimizing discomfort during office-based flexible cystoscopy . METHODS A total of 148 patients were prospect ively r and omized into one of three groups : flexible cystoscopy with no analgesics , a placebo TENS , or an activated TENS . The patient data collected included patient parameters , number of previous flexible cystoscopies , visual analog pain scores during and after the procedure , surgeon 's difficulty rating of procedure , and International Prostate Symptom Score before and 24 hours after the procedure . RESULTS No statistically significant difference was found among the three groups regarding patient parameters . The visual analog pain scores were similar before and after the procedure . At 30 seconds , the mean visual analog scale score for the control group , placebo group , and TENS study group was 3.73 , 3.65 , and 3.52 , respectively ( control versus placebo , control versus active , and placebo versus active : P = 0.97 , 0.29 , and 0.53 , respectively ) . At 1 and 5 minutes , the corresponding scores were 3.44 , 4.37 , and 3.50 ( P = 0.88 , P = 0.99 , and P = 0.99 ) and 0.86 , 1.23 , and 0.88 ( P = 0.97 , P = 0.35 , and P = 0.56 ) , respectively . The surgeon 's mean difficulty rating for the control procedures was 1.08 and for the placebo group was 2.30 ( P = 0.02 ) . CONCLUSIONS All patients undergoing flexible cystoscopy in the office setting experienced discomfort . The TENS device provided no significant benefit for pain . The trend toward greater pain scores in the control group could be attributed to the greater degree of difficulty We evaluated the esophageal acid infusion test ( Bernstein test ) in respect to the following questions : Does chest pain predictably disappear after cessation of acid infusion , and what is the relation between esophageal intraluminal pH and the degree of chest pain relief ? Forty patients with subjective and objective evidence of gastroesophageal acid reflux , in whom esophageal acid infusion had reproduced substernal burning in a mean time of 3.1 minutes + /- 0.8 SE , grade d pain relief after stopping acid infusion when saline was being infused . Complete pain relief occurred in 47.5 % of patients over a 20-minute period . In six patients , esophageal pH was monitored for 30 minutes after administration of saline , antacid , placebo-antacid , and no treatment for a positive acid infusion test . Esophageal pH returned to normal ( greater than 4.0 ) at the same rate ( from 5.0 to 8.3 minutes ) among patients in the four treatment groups , whereas chest pain continued and esophageal pH did not correlate with pain relief . The grading of pain relief was similar among the treatment groups , except at the 5-minute period when antacids result ed in significantly better relief than no treatment In order to evaluate the effect of placebo treatment in congestive heart failure , we retrospectively studied 24 patients with moderately severe congestive heart failure who participated in heart failure treatment trials performed over the past 10 years in the Ohio State University Heart Failure Research Laboratory . Placebo-treated patients from 4 placebo-controlled trials comprised the placebo treatment group ( n = 15 ) , while one natural course-controlled trial provided patients for the non-placebo control group ( n = 9 ) . Changes in symptoms , left ventricular function and exercise duration were assessed following an 8-week course of therapy . Chronic placebo therapy result ed in an 81-second improvement in exercise duration which was statistically significant when compared to pretreatment baseline and to the duration achieved by the nonplacebo control group . Clinical ly , functional class improved significantly by 27 % above baseline only for the placebo treatment group . Indices of left ventricular function did not change for either group . The salient feature of this study is that the placebo treatment effect , while believed to exist in congestive heart failure , has never been demonstrated in a manner which controlled for the natural course and variability of the disease process . The operative components of the placebo effect remain unknown , and further investigation will be necessary to eluci date the underlying mechanisms involved . However , the importance of this phenomenon lies not only with the response to and effects of placebo therapy but also in the role that the placebo effect plays in what is generally presumed to be the predominant responses , effects and benefits of active drug therapy INTRODUCTION Venous leg ulcers ( ulcera crurum venosa ) are frequently seen in elderly patients . It has been suggested that low level laser irradiation has a biostimulative and wound healing effect ; however , this has not yet been clinical ly verified by controlled studies . STUDY DESIGN The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients r and omised into two treatment groups ( 685-nm low level laser and placebo laser ) or a control group which served to quantify the effect of laser application . All patients received st and ardized wound care . OBJECTIVE The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo " light source " . The size of the ulcers was planimetrically measured at baseline ( day 1 ) , at the end of therapy ( day 28 ) and 2 months later ( day 90 ) . The difference in wound size was evaluated . RESULTS There were no statistically significant differences in reduction of wound size between the three groups , thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa |
536 | 26,545,069 | Two broad comparisons were proposed:1 .
periodontal therapy versus no active intervention/usual care;2 .
The evidence was insufficient to conclude whether any of the treatments were associated with harm .
Studies showed varying degrees of success with regards to achieving periodontal health , with some showing high levels of residual inflammation following treatment .
Statistically significant improvements were shown for all periodontal indices ( BOP , CAL , GI , PI and PPD ) at 3 - 4 and 6 months in comparison 1 ; however , this was less clear for individual comparisons within the broad category of comparison 2 .
There was no evidence to support that one periodontal therapy was more effective than another in improving glycaemic control in people with diabetes mellitus .
In clinical practice , ongoing professional periodontal treatment will be required to maintain clinical improvements beyond 6 months .
In addition , it will be important in future studies that the intervention is effective in reducing periodontal inflammation and maintaining it at lowered levels throughout the period of observation | BACKGROUND Glycaemic control is a key issue in the care of people with diabetes mellitus ( DM ) .
Periodontal disease is the inflammation and destruction of the underlying supporting tissues of the teeth .
Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease .
This review up date s the previous version published in 2010 .
OBJECTIVES The objective is to investigate the effect of periodontal therapy on glycaemic control in people with diabetes mellitus . | OBJECTIVE To evaluate the effectiveness of community periodontal care intervention in type 2 diabetic patients with chronic periodontitis who participated in community non-communicable diseases management service . METHODS The r and omized controlled and blinded community trial with a duration of six months was design ed to compare effects of " periodontal initial therapy " on group I(22 cases ) , of " professional mechanical tooth cleaning ( PMTC ) , i.e. coronal scaling " on group II(19 cases ) and of " non- clinical therapy " on the control group(25 cases ) . The clinical periodontal indexes , such as probing depth ( PD ) , attachment loss ( AL ) , modified bleeding index ( mBI ) , plaque index ( PLI ) were obtained with a Williams type periodontal probe ; Laboratory examinations including glycosylated haemoglobin A1(HbA1C ) , glucose assay , were conducted . RESULTS The reductions of PD in groups I and II were 0.71 and 0.70 mm , respectively , which was more significant than in control group ( 0.20 mm ) ; the reductions of AL in groups I , II , and control group were 0.86 , 0.57 , and 0.03 mm , respectively , which showed significance in all the three groups . The subjects of groups I and II had 0.56 % and 1.01 % reductions of HbA1C respectively , and the significance was observed in group II . In addition , the improvement of HbA1C values in group II was highly correlated with the decrease in gingivitis ( r=0.51 , P=0.03 ) . CONCLUSION The community periodontal care approaches implemented in the community health service centers have significantly improved periodontal health as well as reduced glycemic level , which could be regarded as basic health care strategies for the patients with diabetes AIM The aim of this r and omized controlled clinical trial was to evaluate the clinical effects of chlorhexidine ( CHX ) application in a full-mouth disinfection ( FMD ) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis . MATERIAL AND METHODS Thirty-eight subjects were r and omly assigned into FMD group ( n=19 ) : full-mouth scaling and root planing ( FMSRP ) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group ( n = 19 ) : FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days . Clinical parameters , glycated haemoglobin and fasting plasma glucose were assessed at baseline , 3 , 6 and 12 months post-therapies . RESULTS All clinical parameters improved significantly at 3 , 6 and 12 months post-therapies for both groups ( p < 0.05 ) . There were no significant differences between groups for any clinical parameters , and glycemic condition at any time-point ( p > 0.05 ) . CONCLUSIONS The treatments did not differ with respect to clinical parameters , including the primary outcome variable ( i.e. changes in clinical attachment level in deep pockets ) , for up to 12 months post-treatments Background 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Methods 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Results 15 subjects from NSPT group and 17 from OHI group completed the study . The difference in plaque index ( PI ) between NSPT and OHI groups were significant at 2 months recall ( p = 0.013 ) . There was no significant difference between NSPT and OHI group for all other clinical periodontal parameters , HbA1c and CRP levels . At 3 months post-therapy , periodontal parameters improved significantly in both groups with sites with probing pocket depth ( PPD ) < 4 mm reported as 98 ± 1.8 % in NSPT group and 92 ± 14.9 % in OHI group . Mean PPD and mean probing attachment loss ( PAL ) within the NSPT group reduced significantly from baseline ( 2.56 ± 0.57 mm , 3.35 ± 0.83 mm ) to final visit ( 1.94 ± 0.26 mm , 2.92 ± 0.72 mm ) ( p = 0.003 , p < 0.001 ) . For OHI group , improvements in mean PPD and mean PAL were also seen from baseline ( 2.29 ± 0.69 mm , 2.79 ± 0.96 mm ) to final visit ( 2.09 ± 0.72 mm , 2.62 ± 0.97 mm ) ( p < 0.001 for both ) . Similarly , HbA1c levels decreased in both groups with NSPT group recording statistically significant reduction ( p = 0.038 ) . Participants who demonstrated ≥ 50 % reduction in PPD showed significant reductions of HbA1c and hs-CRP levels ( p = 0.004 and p = 0.012 ) . Conclusion NSPT significantly reduced PI at 2 months post-therapy as compared to OHI . Both NSPT and OHI demonstrated improvements in other clinical parameters as well as HbA1c and CRP levels . Trial registration Clinical Trials.gov : NCT01951547 BACKGROUND AND OBJECTIVE Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control . The purpose of this study was to determine the effect of full-mouth tooth extraction on glycemic control among type 2 diabetic patients . MATERIAL AND METHODS A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were r and omized consecutively into treatment ( full-mouth tooth extraction ) and control groups ( no treatment ) . Eight patients were lost to follow-up or reported use of antibiotics , leaving 50 patients to be included in the analysis . All patients had all their remaining teeth in a hopeless condition . Relevant data were collected , and glycosylated hemoglobin ( HbA(1c ) ) and fasting blood glucose levels were measured at baseline and at follow-up times of 3 and 6 mo . RESULTS At baseline , the mean ( SD ) HbA(1c ) level was 8.6 % ( 1.24 ) in the treatment group and 7.7 % ( 0.87 ) in the control group . In the treatment group , the mean HbA(1c ) level decreased significantly from 8.6 % at baseline to 7.4 % after 3 mo of denture treatment , and continued to decrease to 7.3 % after 6 mo . In the control group , the mean HbA(1c ) decreased from 7.7 % at baseline to 7.5 % after 3 mo , and remained almost the same after 6 mo . After adjusting for the baseline HbA(1c ) , the mean reduction in HbA(1c ) after 3 mo in the treatment group [ 1.23 % ( 0.79 ) ] was significantly higher than the mean reduction in the control group [ 0.28 % ( 0.87 ) ] . CONCLUSION Full-mouth tooth extraction result ed in an improvement in glycemic control among diabetic patients . Large-scale multicentre clinical trials are needed to confirm the current evidence A controlled cross-sectional study with the aim of study ing oral health in patients with type 2 diabetes was carried out in a health care district in Sweden . The study included 102 r and omly sample d diabetic patients and 102 age- and gender-matched non-diabetic subjects from the same geographical area , treated at the same Public Dental Service clinics . Oral conditions were measured at clinical and X-ray examinations . Diabetes-related variables were extracted from medical records . Diabetic patients suffered from xerostomia ( dry mouth ) to a significantly higher degree than non-diabetic controls did ( 53.5 vs. 28.4 % ; P=0.0003 ) . Sites with advanced periodontitis were more frequent in the diabetic group ( P=0.006 ) as were initial caries lesions ( P=0.02 ) . Diabetic subjects showed a greater need of periodontal treatment ( P=0.05 ) , caries prevention ( P=0.002 ) and prosthetic corrections ( P=0.004 ) . Diabetes duration or metabolic control of the disease was not related to periodontal status . However , patients with longer duration of diabetes had more manifest caries lesions ( P=0.05 ) as had those on insulin treatment when compared with patients on oral/diet or combined treatment ( P=0.0001 ) . The conclusion is that individuals with type 2 diabetes in some oral conditions exhibited poorer health . Close collaboration between the patient , the primary health care and oral health professionals could be a way of improving the diabetic patient 's general and oral health The aim of this study was to evaluate changes in clinical parameters and levels of inflammatory biomarkers in plasma in periodontal patients with poorly controlled type 2 diabetes mellitus ( T2DM ) after non-surgical periodontal therapy . Twenty-eight poorly controlled T2DM patients were r and omly assigned to treatment with scaling and root planning ( SRP ) and SRP + subgingival minocycline administration . Clinical parameters , including the probing depth ( PD ) , bleeding on probing ( BOP ) , plaque score ( PS ) , clinical attachment level ( CAL ) , and plasma interleukin (IL)-6 , soluble receptor of advanced glycation end products ( sRAGE ) , chronic reactive protein ( CRP ) , and hemoglobin A1c ( HbA1c ) were measured before and after a 6-month treatment period . Significant changes in PD , BOP , PS , and CAL were found in both groups . The latent growth curve model showed an overall reduction in the log HbA1c level in the SRP group ( −0.082 , p = 0.033 ) . Small changes in the log sRAGE level and log CRP level in plasma were found in both groups . IL-6 in the plasma increased in the SRP group , but slightly decreased in the SRP+minocycline group ( 0.469 pg/ml , p = 0.172 ) . Non-surgical periodontal therapy with or without subgingival minocycline application may achieve significant periodontal improvement and moderate improvement in HbA1c , but had no significant effect on plasma levels of IL-6 , CRP , or sRAGE in patients with poorly controlled T2DM . For patients with both periodontal diseases and diabetes , non-surgical periodontal treatments may be helpful in their diabetic control OBJECTIVES We are conducting a clinical trial of the efficacy of periodontal therapy in the improvement of glycaemic control in veterans with poorly controlled diabetes . This report describes study design , recruitment and r and omization and compares baseline characteristics of the sample frame with those r and omized into study groups . METHODS Veterans with poorly controlled diabetes were r and omized in two groups : immediate periodontal therapy ( " early treatment " ) or usual care followed by periodontal therapy ( " deferred treatment " ) . Half of each group continued care for 12 months ; the other half returned to their usual care . We studied baseline patient characteristics , self-reported health measures , and clinical examination data . We examined means for continuous variables , frequencies for categorical variables and compared groups using t-tests and chi(2 ) tests ( alpha=0.05 for both ) . RESULTS The 193 r and omized participants were younger ( 58 years ) and had slightly higher HbA1c ( 10.2 % ) than the 2534 non-r and omized participants ( 64 years , HbA1c = 9.8 % ) . The deferred treatment group was more likely than the early treatment group to have a history of stroke , transient ischaemic attacks , and less likely to be current or former smokers . CONCLUSIONS The mechanism for r and omization was largely successful in this study IMPORTANCE Chronic periodontitis , a destructive inflammatory disorder of the supporting structures of the teeth , is prevalent in patients with diabetes . Limited evidence suggests that periodontal therapy may improve glycemic control . OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin ( HbA1c ) in persons with type 2 diabetes and moderate to advanced chronic periodontitis . DESIGN , SETTING , AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial ( DPTT ) , a 6-month , single-masked , multicenter , r and omized clinical trial . Participants had type 2 diabetes , were taking stable doses of medications , had HbA1c levels between 7 % and less than 9 % , and untreated chronic periodontitis . Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers . INTERVENTIONS The treatment group ( n = 257 ) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months . The control group ( n = 257 ) received no treatment for 6 months . MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months . Secondary outcomes included changes in probing pocket depths , clinical attachment loss , bleeding on probing , gingival index , fasting glucose level , and Homeostasis Model Assessment ( HOMA2 ) score . RESULTS Enrollment was stopped early because of futility . At 6 months , mean HbA1c levels in the periodontal therapy group increased 0.17 % ( SD , 1.0 ) , compared with 0.11 % ( SD , 1.0 ) in the control group , with no significant difference between groups based on a linear regression model adjusting for clinical site ( mean difference , -0.05 % [ 95 % CI , -0.23 % to 0.12 % ] ; P = .55 ) . Periodontal measures improved in the treatment group compared with the control group at 6 months , with adjusted between-group differences of 0.28 mm ( 95 % CI , 0.18 to 0.37 ) for probing depth , 0.25 mm ( 95 % CI , 0.14 to 0.36 ) for clinical attachment loss , 13.1 % ( 95 % CI , 8.1 % to 18.1 % ) for bleeding on probing , and 0.27 ( 95 % CI , 0.17 to 0.37 ) for gingival index ( P < .001 for all ) . CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis . These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00997178 Abstract Objective : To examine the value of glycated haemoglobin ( HbA1c ) concentration , a marker of blood glucose concentration , as a predictor of death from cardiovascular and all causes in men . Design : Prospect i ve population study . Setting : Norfolk cohort of European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) . Subjects : 4662 men aged 45 - 79 years who had had glycated haemoglobin measured at the baseline survey in 1995 - 7 who were followed up to December 1999 . Main outcome measures : Mortality from all causes , cardiovascular disease , ischaemic heart disease , and other causes . Results : Men with known diabetes had increased mortality from all causes , cardiovascular disease , and ischaemic disease ( relative risks 2.2 , 3.3 , and 4.2 , respectively , P < 0.001 independent of age and other risk factors ) compared with men without known diabetes . The increased risk of death among men with diabetes was largely explained by HbA1c concentration . HbA1c was continuously related to subsequent all cause , cardiovascular , and ischaemic heart disease mortality through the whole population distribution , with lowest rates in those with HbA1c concentrations below 5 % . An increase of 1 % in HbA1c was associated with a 28 % ( P<0.002 ) increase in risk of death independent of age , blood pressure , serum cholesterol , body mass index , and cigarette smoking habit ; this effect remained ( relative risk 1.46 , P=0.05 adjusted for age and risk factors ) after men with known diabetes , a HbA1c concentration ≥7 % , or history of myocardial infa rct ion or stroke were excluded . 18 % of the population excess mortality risk associated with a HbA1c concentration ≥5 % occurred in men with diabetes , but 82 % occurred in men with concentrations of 5%-6.9 % ( the majority of the population ) . Conclusions : Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution . Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c through behavioural means In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation . We conducted a 3-month , r and omized placebo-controlled pilot clinical trial of conventional sub-gingival debridement ( periodontal therapy ) , combined with either a three month regimen of sub-antimicrobial-dose doxycycline ( SDD ) , a two week regimen of antimicrobial-dose doxycycline ( ADD ) , or placebo in 45 patients with long-st and ing type 2 diabetes ( mean duration 9 years ) and untreated chronic periodontitis . Subjects were taking stable doses of oral hypoglycemic medications and /or insulin . Treatment response was assessed by measuring hemoglobin A1c ( HbA1c ) , plasma glucose , and clinical periodontal disease measures . At one-month and three-month follow-up , clinical measures of periodontitis were decreased in all groups ( data to be presented elsewhere ) . At three months , mean HbA1c levels in the SDD group were reduced 0.9 % units from 7.2 % units±2.2 ( ±SD ) , to 6.3 % units±1.1 , which represents a 12.5 % improvement . In contrast , there was no significant change in HbA1c in the ADD ( 7.5%±2.0 to 7.8%±2.1 ) or placebo ( 8.5%±2.0 to 8.5%±2.6 ) groups . Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group ( p=0.04 ) but not placebo ( p=0.22 ) . Moreover , a larger proportion of subjects in the SDD group experienced improvement ( p<0.05 ) compared to the ADD or placebo groups . Mean plasma glucose levels were not significantly different between or within the groups . The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents AIM To evaluate the clinical , microbiological and immunological effects of systemic doxycycline as an adjunct to scaling and root planing ( SRP ) in chronic periodontitis patients with well-controlled type 2 diabetes . MATERIAL S AND METHODS Sixty-six patients compliant to oral hygiene ( Hygiene Index < 20 % ) allocated to either a test ( systemic doxycycline for 21 days ) or a control ( placebo ) group participated in the present r and omized controlled trial ( RCT ) . Clinical assessment s were recorded at baseline , 3 and 6 months after therapy and included clinical attachment level ( CAL ) , set as the primary outcome of the study , probing pocket depth ( PPD ) , recession ( RE ) and bleeding on probing ( BOP ) . At the same time points , counts of 15 subgingival species were evaluated by " checkerboard " DNA-DNA hybridization , gingival crevicular fluid sample s were analysed for matrix metalloproteinase-8 ( MMP-8 ) by ELISA and HbA1c levels were determined . Comparisons between and within groups were performed by non-parametric tests ( Mann-Whitney , Wilcoxon signed-ranks and z-test for proportions with Bonferroni corrections ) at the 0.05 level . RESULTS No major differences were noticed in clinical and microbiological parameters of periodontal disease or levels of MMP-8 between the two groups . CONCLUSIONS Adjunctive systemic doxycycline does not seem to significantly enhance the effects of SRP in well-controlled diabetes type 2 patients Current evidence suggests that periodontal infection may aggravate diabetes control . The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a r and omized clinical trial . One hundred and five ( 105 ) patients with diabetes and chronic periodontitis were r and omly assigned to three treatment groups : subgingival mechanical therapy with azithromycin , subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin . Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline , 3 , 6 and 9 months after periodontal therapy . The frequency with which Porphyromonas gingivalis , Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups . Tannerella forsythia increased after3 months in all groups . All organisms had similar frequencies at 9 months in all groups . Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes Background Periodontitis is a common , chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth . Epidemiological studies have consistently shown increased frequency , extent and severity of periodontitis among diabetic adults . More recently , some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients . However current evidence does not provide sufficient information on which to confidently base any clinical recommendations . The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis . Methods The DIAPERIO trial is an open-label , 13-week follow-up , r and omized , controlled trial . The total target sample size is planned at 150 participants , with a balanced ( 1:1 ) treatment allocation ( immediate treatment vs delayed treatment ) . Periodontal treatment will include full mouth non-surgical scaling and root planing , systemic antibiotherapy , local antiseptics ( chlorhexidine 0.12 % ) and oral health instructions . The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks ' follow-up . Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups . Discussion The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis . The results of this trial will help to provide evidence -based recommendations for clinicians and a draft framework for design ing national health policies . Trial registration Current Controlled Trials IS RCT Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists . Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing ( SRP ) improved metabolic control in diabetic patients , as defined by reduction in glycated haemoglobin or reduction in insulin requirements ( Grossi and Genco , 1998 ) . The aim of this r and omised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres ( Arestin ) as an adjunct to scaling and root planing . Twenty adult patients with poorly controlled diabetes ( HbA1c 7.5 % ) and adult periodontitis , as determined by the presence of four teeth with 5 mm periodontal pockets , two of which had 6 - 9 mm pockets and bleeding on probing , were included in the study . All patients received full mouth SRP at baseline . Arestin was administered to all pockets > or = > or = 5 mm at baseline and again at 12 weeks in the test group . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) , gingival index ( GI ) , and HbA1c were evaluated at baseline and at weeks 6 , 12 , 18 and 24 . The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients . Hb1Ac was reduced in all patients ; however the difference between the test and control groups was not significant OBJECTIVE To investigate the effectiveness of short-term adjunctive subantimicrobial dose doxycycline ( SDD ) treatment in patients with diabetes mellitus type 2 and chronic periodontitis ( CP ) . METHODS Thirty-four patients with CP and type 2 diabetes mellitus were included in the placebo-controlled , double-blind study . After scaling and root planing ( SRP ) , patients were r and omly assigned to two groups , receiving either SDD or placebo bid for 3 months . The probing depth ( PD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , approximal plaque index , glycated hemoglobin ( HbA1c ) level were recorded and gingival crevicular fluid ( GCF ) sample s were collected at baseline and after 3-month therapy for the estimation of matrix metalloproteinase-8 levels . RESULTS Clinical attachment level , PD , and BOP improved significantly in both groups after therapy ( P < 0.05 ) . The statistically significant difference between the two groups after the therapy was observed only in PD in tooth sites with initial PD ≥ 4 mm ( SRP + placebo : 3.41 ± 0.6 mm vs SRP + SDD : 2.92 ± 0.5 mm , P < 0.05 ) . GCF matrix metalloproteinase-8 levels were significantly reduced only in SRP + SDD group ( P < 0.01 ) . There were no changes in HbA1c levels after therapy . CONCLUSION The short-term administration of SDD gives significant benefit at tooth sites with moderate disease ( PD ≥ 4 mm ) when compared to SRP alone in patients with diabetes and CP Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus . The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes . A total of 113 Native Americans ( 81 females and 32 males ) suffering from periodontal disease and non-insulin dependent diabetes mellitus ( NIDDM ) were r and omized into 5 treatment groups . Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens : 1 ) topical water and systemic doxycycline , 100 mg for 2 weeks ; 2 ) topical 0.12 % chlorhexidine ( CHX ) and systemic doxycycline , 100 mg for 2 weeks ; 3 ) topical povidone-iodine and systemic doxycycline , 100 mg for 2 weeks ; 4 ) topical 0.12 % CHX and placebo ; and 5 ) topical water and placebo ( control group ) . Assessment s were performed prior to and at 3 and 6 months after treatment and included probing depth ( PD ) , clinical attachment level ( CAL ) , detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin ( HbA1c ) . After treatment all study groups showed clinical and microbial improvement . The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group . In addition , all 3 groups receiving systemic doxycycline showed , at 3 months , significant reductions ( P < or = 0.04 ) in mean HbA1c reaching nearly 10 % from the pretreatment value . Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin . Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients AIMS : The purpose of this study is to investigate the effect of improved periodontal health on glycemic control in type 2 diabetes mellitus ( type 2 DM ) patients who have generalized periodontitis . MATERIAL S AND METHODS : A total of 45 type 2 DM patients with generalized periodontitis were selected for the study . The selected patients were r and omly assigned to three groups ( groups A , B , and C ) comprising 15 patients each : • Group A received treatment with scaling and root planing only . • Group B received treatment with scaling and root planing followed by systemic doxycycline . • Group C received no treatment ( control group ) . The periodontal parameters recorded included plaque index , gingival index , probing pocket depth , and clinical attachment level . These parameters were recorded at baseline ( day zero ) , at 1 month , and at the end of 3 months . The following metabolic parameters were recorded : fasting blood glucose ( FBG ) , postpr and ial blood glucose ( PPBG ) , and glycated hemoglobin . These were recorded at baseline ( day zero ) and at the end of 3 months . STATISTICAL ANALYSIS : All the parameters were subjected to repeated- measures ANOVA and Scheffe 's post hoc test . RESULTS : A statistically significant effect could be demonstrated for periodontal parameters for both group A and group B ( treatment groups ) . Glycated hemoglobin values showed statistically significant decrease in treatment groups compared to the control group , with group B showing more significant decrease than group A. CONCLUSIONS : The results of this study showed that nonsurgical periodontal treatment is associated with improved glycemic control in type 2 DM patients BACKGROUND Periodontitis is a major cause of tooth loss among adults . Several studies have shown a possible systemic impact of periodontal infection , including poor glycemic control in patients with diabetes . Recently , photodynamic therapy ( PDT ) was used to successfully treat periodontal infection . PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects . The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis . METHODS Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and r and omly assigned to one of the following three treatment modalities ( 15 subjects each ) : scaling and root planing ( SRP ) only , SRP plus systemic doxycycline , and SRP plus PDT . The plaque and bleeding scores , probing depth , clinical attachment level , and glycosylated hemoglobin ( HbA1c ) level were recorded at baseline and 3 months after periodontal treatment . Descriptive statistics , the paired t test , and analysis of variance ( ANOVA ) were used for data analysis . RESULTS Statistically significant differences in the mean probing depth , clinical attachment level , plaque deposit , and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups . No significant differences in periodontal parameters and glucose levels were detected among the three groups . Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group . CONCLUSION The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes BACKGROUND , AIMS This study was design ed to explore the effect of periodontal therapy on glycemic control in persons with type 2 diabetes mellitus ( DM ) . METHODS 36 patients with type 2 DM ( treatment group ) received therapy for adult periodontitis during an 18-month period . A 36-person control group was r and omly selected from the same population of persons with type 2 DM who did not receive periodontal treatment . RESULTS These groups were well matched for most of the parameters investigated . During the nine-month observation period , there was a 6.7 % improvement in glycemic control in the control group when compared to a 17.1 % improvement in the treatment group , a statistically significant difference . Several parameters that could confound or moderate this glycemic control were explored . These included the treatment of non-dental infections , weight and medication changes . No moderating effect was associated with any of these variables . However , there were too few subjects in the study to have the statistical power necessary to assess these possible moderators of glycemic control . CONCLUSIONS We interpret the data in the study to suggest that periodontal therapy was associated with improved glycemic control in persons with type 2 DM AIM The purpose of this pilot study was to determine and compare the effects of two protocol s aim ed at reducing periodontal inflammation , upon the metabolic control of the diabetic condition in subjects with elevated baseline glycosylated hemoglobin ( HbA1c ) . METHODS AND MATERIAL S Forty-two non-smoking type 2 diabetes subjects with mildly elevated HbA1c ( > 7 but < 9 % ) and severely elevated ( > 9 % ) were r and omized to one of two non-surgical periodontal therapy protocol s. Patients in the " minimal therapy " ( MT ) group received scaling , root planning , and oral hygiene instructions on two occasions six months apart . Participants r and omized to the " frequent therapy " ( FT ) protocol received scaling , root planing , and oral hygiene instructions at two-month intervals and were provided a 0.12 % chlorhexidine rinse for home use twice daily . Neither systemic nor local antibiotics were provided to either group . Subjects were asked to report any changes in diabetic medications , nutrition , and physical activity . Data analyses ( ANOVA , t-test , Mann-Whitney ) grouped subjects according to baseline HbA1c ( > 7 and < 9 % , or > 9 % ) , treatment protocol ( minimal or frequent ) , and + /- medication change . RESULTS In both MT and FT groups the clinical attachment level ( CAL ) remained unchanged but the other measures [ gingival index ( GI ) and pocket dept ( PD ) ] of periodontal health improved . Mean reductions in plaque showed improvement but calculus was worse in the FT group , likely due to the use of chlorhexidine . At six months , the largest reduction of HbA1c was 3.7 ; experienced by a subject receiving FT but no changes in diabetic medication . Among the MT and no medication change subjects , the maximum reduction was 1.6 . Overall mean reduction in HbA1c of 27 subjects with baseline HbA1c > 9.0 and no medication change was 0.6 with no statistical difference between the MT and FT groups . Among the medication-change subjects with baseline HbA1c > 9.0 , mean reduction of 1.38 was seen with FT compared to 1.10 with MT . CONCLUSION Overall , modest improvements in HbA1c were detected with a trend towards FT being better than MT . Although this pilot trial was under-powered to detect small between-group differences , the magnitude of our findings ( 0.6 mean improvement in HbA1c ) matches closely findings from the only meta- analysis conducted on this topic to date . Larger scale studies must be undertaken on diabetic patients with periodontal problems . CLINICAL SIGNIFICANCE Preventive periodontal regimens for diabetic patients should be sufficiently intense and sustained to eliminate periodontal inflammation and should be closely coordinated with the patient 's overall clinical diabetic management Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) AIM the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis . MATERIAL S AND METHODS this was a r and omized , controlled clinical trial of patients with type 2 diabetes . A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm , consisting of scaling and root planing ( intervention group [ IG ] ) , or a delayed treatment arm that received periodontal care after 6 months ( control group [ CG ] ) . Periodontal parameters and glycosylated haemoglobin ( A1C ) were evaluated at 1 , 3 and 6 months . RESULTS all periodontal parameters improved significantly in the IG . A1C levels decreased statistically significantly more in the IG versus the CG ( 0.72%versus 0.13 % ; p<0.01 ) independently of other confounders . CONCLUSIONS this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients . Larger controlled trials are needed to confirm if this finding is generalizable to other population s of patients with type 2 diabetes AIM To examine associations of pre-diabetes and well-controlled diabetes with periodontitis . MATERIAL S AND METHODS The Study of Health in Pomerania (SHIP)-Trend is a cross-sectional survey in North-Eastern Germany including 3086 participants ( 49.4 % men ; age 20 - 82 years ) . Clinical attachment loss ( CAL ) and periodontal probing depth ( PPD ) were assessed applying a r and om half-mouth protocol . The number of teeth was determined . Pre-diabetes comprised impaired fasting glucose and impaired glucose tolerance . Previously known diabetes was defined as well controlled if glycated haemoglobin ( HbA1c ) was < 7.0 % . Participants were categorized as follows : normal glucose tolerance ( NGT ) , pre-diabetes , newly detected type 2 diabetes ( T2DM ) , known T2DM with HbA1c<7.0 % and known T2DM with HbA1c≥7.0 % . RESULTS Pre-diabetes was neither associated with mean CAL and PPD in multivariable adjusted linear regression models nor with edentulism ( OR = 1.09 ( 95%-CI : 0.69 - 1.71 ) ) and number of teeth ( OR = 0.96 ( 95%-CI : 0.75 - 1.22 ) , lowest quartile versus higher quartiles ) in logistic regression models . Associations with mean CAL and edentulism were stronger in poorly controlled previously known diabetes than in well-controlled previously known diabetes ( for edentulism : OR = 2.19 ( 95%-CI : 1.18 - 4.05 ) , and OR = 1.40 ( 95%-CI : 0.82 - 2.38 ) , respectively , for comparison with NGT ) . CONCLUSIONS Periodontitis and edentulism were associated with poorly controlled T2DM , but not with pre-diabetes and well-controlled diabetes UNLABELLED The AIM of this study was to evaluate the effect of non-surgical therapy on clinical variables and glycemic control on type 2 diabetics with chronic periodontitis . PATIENTS AND METHODS Forty six type 2 diabetics with chronic periodontitis were r and omized into two groups ( group A and group B ) . Treatment included scaling and root planning for group A plus systematic use of doxycycline in both groups . Assessment was made prior to and 16 weeks following the therapy . RESULTS Analysis of data showed that both groups had clinical and glycated hemoglobin ( HbAlc ) improvement after the treatment . Group A had a statistically significant reduction of plaque index and bleeding on probing scores compared with controls ( P < 0.05 ) at 16 weeks . CONCLUSION These results suggest that non-surgical therapy is of value in maintaining periodontal health and may be beneficial in reducing blood glucose level in type 2 diabetics with chronic periodontitis BACKGROUND The literature suggests that an alteration in glucose metabolism occurs as a result of antibacterial periodontal therapy . The objective of this study was to monitor the effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus ( DM ) . METHODS Thirty type 2 DM subjects with periodontitis were r and omly divided into two groups . Group 1 ( G1 ) , 15 subjects , received one-stage full-mouth scaling and root planing ( FMSRP ) plus amoxicillin/clavulanic acid 875 mg ; group 2 ( G2 ) , 15 patients , received only FMSRP . At baseline and after 3 months , the glycated hemoglobin ( HbA1c ) values , fasting glucose , and clinical parameters ( with computerized probing and individualized acrylic stents ) were recorded . Following therapy , the subjects were enrolled in a 2-week interval maintenance program for 3 months . RESULTS After treatment , both groups showed clinical improvements . A probing depth ( PD ) reduction of 0.8 + /- 0.6 mm ( P < 0.05 ) occurred in G1 and 0.9 + /- 0.4 mm in G2 ( P < 0.05 ) , but there were no significant changes in attachment level . Treatment reduced the HbA1c values after the 3-month observation period in both groups ; however , the reduction in HbA1c values for the G2 group was statistically significant , but not for the G1 group . The changes in fasting glucose levels were not significant for either group . CONCLUSIONS Periodontal therapy improved glycemic control in patients with type 2 DM in both groups ; however , the reduction in HbA1c values reached statistical significance only in the group receiving scaling and root planing alone [ correction ] PURPOSE To assess the impact of empowerment ( health coaching , HC ) on toothbrushing self-efficacy ( TBSE ) and toothbrushing frequency ( TB ) and their effects on diabetes management ( HbA1c , physical activity ) and quality of life in comparison to health education ( HE ) among patients with diabetes type 2 ( DM2 ) . MATERIAL S AND METHODS The data ( HbA1c [ glycated haemoglobin ] , TB , physical activity , TBSE , quality of life ) were collected at baseline and at post-intervention at outpatient clinics of two hospitals in Istanbul , Turkey . Participants were allocated r and omly to HC ( n = 77 ) and HE ( n = 109 ) groups . RESULTS At baseline , there were no statistical differences between HC and HE groups in terms of all measures ( P > 0.05 ) . At post-intervention , there was improvement in oral health- and diabetes-related variables in the HC group , whereas only TBSE and TB slightly improved in the HE group ( P < 0.05 ) . At post-intervention among patients brushing their teeth at least once a day , HC group patients were more likely to be physically active and to have high self-efficacy than those in HE group ( P < 0.01 ) . TBSE was correlated with favourable HbA1c levels ( < 6.5 % ) in the HC group and quality of life ( P < 0.05 ) in both groups . CONCLUSION The findings show that HC-based empowerment towards improving self-efficacy is more effective at improving toothbrushing behaviour than is HE and that interaction contributes significantly to diabetes management in terms of reduced HbA1c , increased physical activity and quality of life . TBSE can be a practical starting point for empowerment and toothbrushing can be used as an effective and practical behaviour to observe personal success in diabetes management AIM The purpose of this study was to assess the response of diabetics to scaling and root planing treatment and subgingival oral irrigation as adjunctive therapy . METHOD A total of 52 type 1 and 2 diabetics ( mean age 51.3+/-14 ) with adult periodontitis were r and omized to two groups . Treatment included ultrasonic scaling and scaling and root planing in both groups ( control and test ) plus subgingival water irrigation 2x daily for the test group . Assessment s were made prior to and at 6 and 12 weeks after treatment . Parameters measured were modified gingival index ( MGI ) , probing pocket depth ( PPD ) , plaque index ( PI ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) . Systemic measurement of Reactive Oxygen Species ( ROS ) generation , cytokines ( TNF-alpha , IL-1beta , IL-10 , and PGE2 ) , and glycated hemoglobin ( HbA1C ) . RESULTS After treatment , analysis of data showed that both groups had clinical and systemic improvement . The test group had a statistically significant reduction for MGI , PI , and BOP compared to controls ( p<0.03 ) at 12 weeks and for ROS generation at 12 weeks ( p<0.012 ) . Unlike controls , systemic analysis of cytokines showed a statistically significant reduction from baseline for IL-1beta at 6 weeks and PGE2 at 6 and 12 weeks ( p<0.05 ) within test group . CONCLUSION These results suggest that scaling and root planing and adjunctive therapy may be of value in establishing a healthy periodontium in diabetics OBJECTIVES Report results of a r and omized- clinical trial of the efficacy of periodontal care in the improvement of glycemic control in 165 veterans with poorly controlled diabetes over 4 months . METHODS Outcomes were change in Haemoglobin A1c ( HbA1c ) in the Early Treatment versus untreated ( Usual Care ) groups and percent of participants with decreases in HbA1c . Analyses included simple/multiple variable linear/logistic regressions , adjusted for baseline HbA1c , age , and duration of diabetes . RESULTS Unadjusted analyses showed no differences between groups . After adjustment for baseline HbA1c , age , and diabetes duration , the mean absolute HbA1c change in the Early Treatment group was -0.65 % versus -0.51 % in the Usual Care group ( p=0.47 ) . Adjusted odds for improvement by 0.5 % in the Early Treatment group was 1.67 ( 95 % confidence interval : 0.84 , 3.34 , p=0.14 ) . Usual Care subjects were twice as likely to increase insulin from baseline to 4 months ( 20 % versus 11 % , p=0.12 ) and less likely to decrease insulin ( 1 % versus 6 % , p=0.21 ) than Early Treatment subjects . Among insulin users at baseline , more increased insulin in the Usual Care group ( 40 % versus 21 % , p=0.06 ) . CONCLUSIONS No significant benefit was found for periodontal therapy after 4 months in this study ; trends in some results were in favour of periodontal treatment AIM The present investigation was performed to study how type 1 diabetics responded to non-surgical periodontal treatment with and without adjunctive doxycycline . METHOD Sixty diabetic type 1 patients ( mean age 35.3+/-9 years ) with moderate-to-severe periodontal disease were selected and divided into two groups of 30 patients each . Both groups were sex and age matched and had similar amounts of periodontal destruction . Plaque index ( PI ) , bleeding on probing ( BOP ) , probing depth ( PD ) and clinical attachment levels ( CAL ) were recorded . Group 1 ( 30 patients ) was treated with oral hygiene instruction , scaling and root planing , chlorhexidine rinses twice a day and doxycycline ( 100 mg/day for 15 days ) . Group 2 ( 30 patients ) had the same treatment but without doxycycline . After 12 weeks their periodontal condition was reevaluated . RESULTS After treatment , both groups had a significant improvement in all periodontal parameters , since PI , BOP , probing pocket depth ( PPD ) and CAL were significantly reduced . However , the reduction in PD in pockets > or = 6 mm and in BOP were more evident when doxycycline was used ( group 1 ) . Differences between groups for these parameters were statistically significant ( p=0.03 ) . CONCLUSION Although both periodontal treatment regimens are effective in type 1 diabetics , the use of doxycycline as an adjunct , provided more significant results when good plaque control was achieved BACKGROUND Type 2 diabetes mellitus ( T2DM ) is a growing health problem worldwide . People with T2DM are at risk of experiencing periodontitis and likely require treatment . Using data from the national multicenter Diabetes and Periodontal Therapy Trial ( DPTT ) , the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy . METHODS The DPTT investigators r and omly assigned adults with T2DM ( hemoglobin A1c [ HbA1c ] ≥ 7 percent and < 9 percent ) and moderate to advanced periodontitis to receive immediate or delayed therapy ( scaling and root planing , oral hygiene instruction , chlorhexidine rinse ) . The investigators assessed probing depth ( PD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , and medical conditions at baseline , three months and six months . Six-month changes in mean PD , CAL and BOP defined the treatment response . Complete data were available for 473 of 514 DPTT participants . The authors used multiple regression models to evaluate participant-level factors associated with the response . RESULTS More severe baseline PD , CAL and BOP were associated with greater improvements in these same measurements ( P < .0001 ) . Hispanic participants experienced greater improvements in PD and CAL than did non-Hispanic participants ( P < .0001 ) . Obese participants ( those with a body mass index > 30 kilograms per square meter ) experienced greater reductions in PD and BOP than did participants who were not obese ( P < .001 ) . Age , sex , HbA1c values , diabetes duration , and smoking were not associated with change in any outcome ( P > .1 ) . CONCLUSIONS In patients with T2DM , baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy . Body mass index and Hispanic ethnicity-but not glycemic control , diabetes duration or smoking-also may be useful in predicting clinical changes in this population BACKGROUND AND OBJECTIVE Periodontitis may alter the systemic condition in patients with diabetes and hence interfere with glycemic control . The objective of this study was to determine the quantifiable changes in glycated hemoglobin ( HbA1C ) after periodontal non-surgical therapy plus azithromycin in a mixed population of patients with poorly controlled diabetes . MATERIAL S AND METHODS One hundred and five patients were r and omized to receive non-surgical therapy plus azythromycin ( AZ-Sca = 33 ) , non-surgical therapy plus placebo ( PB-Sca = 37 ) and supragingival prophylaxis plus azithromycin ( AZ-Pro = 35 ) . Glycated hemoglobin , glycemia and periodontal parameters were measured at baseline , 3 , 6 and 9 mo after treatment . RESULTS Periodontal parameters were improved in the AZ-Sca and PB-Sca groups as compared to the AZ-Pro group . A greater reduction in probing depth was observed in the AZ-Sca as compared to the PB-Sca group . Improvement in clinical attachment level was similar between AZ-Sca and PB-Sca groups . A reduction from 8.0 % to 7.2 % ( ∆0.8 % ; p < 0.05 ) in HbA1C was observed in the AZ-Sca at 9 mo as compared to the PB-Sca group in which the reduction was from 7.9 % to 7.6 % ( ∆0.3 % ) . There was no decrease in HbA1C in the AZ-Pro group over time . Mean glycemia values decreased from 195 mg/dL to 159.2 mg/dL ( ∆35.8 mg/dL ; p < 0.05 ) in the AZ-Sca group whereas a decrease from 194 mg/dL to 174.8 mg/dL ( ∆19.2 mg/dL ) in the PB-Sca group at 9 mo was observed . There were no differences between the AZ-Sca and PB-Sca groups for glycemic parameters . No improvement in glycemic values in the AZ-Pro group was observed . CONCLUSIONS A modest improvement in glycemic control was detected with a trend towards the use of non-surgical therapy plus AZ as compared to the placebo BACKGROUND Alendronate ( ALN ) is an aminobisphosphonate commonly used for osteoporosis in postmenopausal women . We studied the effect of ALN on bone loss prevention in type 2 diabetes mellitus patients with periodontal disease . METHODS In a controlled double-blind , r and omized study we evaluated prospect ively diabetic patients paired by gender and years since diagnosis for 6 months . The study included 40 patients ( 20 men and 20 women ) , 50 to 60 years old , with more than 5 years since diagnosis of diabetes and established periodontitis . They were r and omly allocated to alendronate ( 10 mg/daily ) or placebo treatment for 6 months . The endpoints of treatment were : the distance between the alveolar bone border and the cemento-enamel-junction ( CEJ ) evaluated by means of digital radiographic imaging , a biochemical marker of bone resorption ( urine N-telopeptide ) ( Ntx ) , and periodontal parameters . Metabolic control was assessed at baseline and after 6 months . RESULTS Baseline and 6-month glycated hemoglobin levels were similar in both groups . Alendronate induced a significant decrease in NTx at 6 months ( P = 0.006 ) . Periodontal parameters improved in both groups . However , they were significantly better for the ALN treated group . Alveolar bone border-CEJ distance increased in the placebo , but decreased in the ALN group ( P = 0.0003 ) . CONCLUSIONS In type-2 diabetic patients , alendronate induced more improvement in alveolar bone crest height than control therapy . No differences in urinary N-telopeptide or glycated hemoglobin were observed in this short-term r and omized controlled pilot trial OBJECTIVE In the Mexican-American population , the prevalence of Type 2 diabetes mellitus ( T2DM ) is as high as 50 % of the population . This r and omized controlled clinical trial was design ed to eluci date how treatment of periodontal disease affects HbA1c values in this population . MATERIAL S AND METHODS One hundred and fifty-four T2DM patients with periodontal disease were enrolled in the study . The test group was treated with scaling and root planing ( SRP ) ; the control group received oral hygiene instructions . At baseline and 4 - 6 weeks after therapy , a complete periodontal examination was performed . Blood was collected at baseline and 4 months later for HbA1c levels . RESULTS One hundred and twenty-six individuals completed the study . Baseline mean ± SD HbA1c for the test and control groups were 9.0 ± 2.3 % and 8.4 ± 2.0 % respectively . Non-significant difference in HbA1c reductions ( 0.6 ± 2.1 % and 0.3 ± 1.7 % ) was found between test and control groups at 4 months . Comparisons of the periodontal clinical parameters between the test and control groups found significant differences with improved results in the test subjects . CONCLUSIONS No statistically significant differences were found in the changes of HbA1c levels between test and control groups . Non-surgical periodontal therapy improved the magnitude of change in periodontal parameters as compared to the control subjects . Clinical Trials.gov Identifier : NCT01128374 AIM To evaluate the clinical and microbiological effects of the use of metronidazole ( MTZ ) + amoxicillin ( AMX ) as adjuncts to scaling and root planing ( SRP ) for the treatment of chronic periodontitis ( ChP ) in type 2 diabetic subjects . MATERIAL AND METHODS Fifty-eight type 2 diabetic subjects ( n = 29/group ) with generalized ChP were r and omly assigned to receive SRP alone or with MTZ [ 400 mg/thrice a day (TID)]+AMX ( 500 mg/TID ) for 14 days . Subgingival biofilm sample s were analyzed by qPCR for the presence of seven periodontal pathogens . Subjects were monitored at baseline , 3 , 6 and 12 months post-therapies . RESULTS The group receiving SRP+MTZ+AMX presented greater mean probing depth ( PD ) reduction and clinical attachment gain , a lower number of sites with PD ≥5 mm ( primary outcome variable ) and a reduced number of subjects with ≥9 of these residual pockets than the control group at 1-year post-therapy ( p < 0.05 ) . The antibiotic-treated group also presented reduced levels and greater decreases of the three red complex species , Eubacterium nodatum and Prevotella intermedia , compared to the control group at 1 year ( p < 0.05 ) . CONCLUSIONS The adjunctive use of MTZ+AMX significantly improved the clinical and microbiological outcomes of SRP in the treatment of type 2 diabetic subjects with BACKGROUND Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus ( T2DM ) , raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM . Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin ( Hb ) A1c . PURPOSE The purpose of the Diabetes and Periodontal Therapy Trial ( DPTT ) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis . METHODS DPTT was a phase-III , single-masked , multi-center , r and omized trial with a planned enrollment of 600 participants . Participants were r and omly assigned to receive periodontal treatment immediately ( Treatment Group ) or after 6 months ( Control Group ) . HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following r and omization . Medication usage and dosing were assessed at each visit . Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions , plus the use of an antibacterial mouth rinse for at least 32 days afterwards . The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6 % . Secondary outcomes included changes in periodontal clinical measures , fasting plasma glucose , the Homeostasis Model Assessment ( HOMA2 ) and the need for rescue diabetes or periodontal therapy . CONCLUSION Dental and medical research ers collaborated to recruit , treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other |
537 | 27,546,228 | Providing healthcare professionals with a tool to improve implementation of a guideline may lead to little or no difference in costs to the health service .
Implementation tools developed by recognised guideline producers probably lead to improved healthcare professionals ' adherence to guidelines in the management of non-specific low back pain and ordering thyroid-function tests .
There are limited data on the relative costs of implementing these interventions .There are no studies evaluating the effectiveness of interventions targeting the organisation of care ( e.g. benchmarking tools , costing templates , etc .
We could not draw any conclusions about our second objective , the comparative effectiveness of implementation tools , due to the small number of studies , the heterogeneity between interventions , and the clinical conditions that were targeted | BACKGROUND The uptake of clinical practice guidelines ( CPGs ) is inconsistent , despite their potential to improve the quality of health care and patient outcomes .
Some guideline producers have addressed this problem by developing tools to encourage faster adoption of new guidelines .
This review focuses on the effectiveness of tools developed and disseminated by guideline producers to improve the uptake of their CPGs .
OBJECTIVES To evaluate the effectiveness of implementation tools developed and disseminated by guideline producers , which accompany or follow the publication of a CPG , to promote uptake .
A secondary objective is to determine which approaches to guideline implementation are most effective .
These studies evaluated the effects of tools developed by national guideline producers to implement their CPGs . | Background To strengthen suicide prevention skills in mental health care in The Netherl and s , multidisciplinary teams throughout the country are trained in the application of the new Dutch guideline on the assessment and treatment of suicidal behavior . Previous studies have shown beneficial effects of additional efforts for guideline implementation on professionals ’ attitude , knowledge , and skills . However , the effects on patients are equally important , but are rarely measured . The main objective of this study is to examine whether patients of multidisciplinary teams who are trained in guideline application show greater recovery from suicide ideation than patients of untrained teams . Methods / Design This is a multicentre cluster r and omized controlled trial ( RCT ) , in which multidisciplinary teams from mental health care institutions are matched in pairs , and r and omly allocated to either the experimental or control condition . In the experimental condition , next to the usual dissemination of the guideline ( internet , newsletter , books , publications , and congresses ) , teams will be trained in the application of the guideline via a 1-day small interactive group training program supported by e-learning modules . In the control condition , no additional actions next to usual dissemination of the guideline will be undertaken . Assessment s at patient level will start when the experimental teams are trained . Assessment s will take place upon admission and after 3 months , or earlier if the patient is discharged . The primary outcome is suicide ideation . Secondary outcomes are non-fatal suicide attempts , level of treatment satisfaction , and societal costs . Both a cost-effectiveness and cost-utility analysis will be performed . The effects of the intervention will be examined in multilevel models . Discussion The strengths of this study are the size of the study , RCT design , training of complete multidisciplinary teams , and the willingness of both management and staff to participate . Trial registration Netherl and s trial register : Background Interventions design ed to narrow the gap between research findings and clinical practice may be effective , but also costly . Economic evaluations are necessary to judge whether such interventions are worth the effort . We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs . The tailored intervention was evaluated in a r and omized trial , and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication , but had little or no impact on other outcomes . The increased use of thiazides was not expected to have an impact on health outcomes . Methods and Findings We performed cost-minimization and cost-effectiveness analyses on data from a r and omized trial involving 146 general practice s from two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Only patients that were being started on antihypertensive medication were included in the analyses . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders . Pharmacists conducted the visits . A cost-minimization framework was adopted , where the costs of intervention were set against the reduced treatment costs ( principally due to increased use of thiazides rather than more expensive medication ) . The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides . The net annual cost ( cost minimization ) in our study population was US$ 53,395 , corresponding to US$ 763 per practice . The cost per additional patient started on thiazides ( cost-effectiveness ) was US$ 454 . The net annual savings in a national program was modeled to be US$ 761,998 , or US$ 540 per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted , and the cost-effectiveness was estimated to be US$ 183 . Conclusions We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial . A major reason to promote the use of thiazides is their lower price compared to other drugs . The cost of the intervention was more than twice the savings within the time frame of our study . However , we predict modest savings over a 2-y period Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions Background A r and omised trial of a multifaceted intervention for improving adherence to clinical practice guidelines for the pharmacological management of hypertension and hypercholesterolemia increased prescribing of thiazides , butdetected no impact onthe use of cardiovascular risk assessment toolsor achievement of treatment targets . We carried out a predominantly quantitative process evaluation to help explain and interpret the trial- findings . Methods Several data - sources were used including : question naires completed by pharmacists immediately after educational outreach visits , semi-structured interviews with physicians subjected to the intervention , and data extracted from their electronic medical records . Multivariate regression analyses were conducted to explore the association between possible explanatory variables and the observed variation across practice s for the three main outcomes . Results The attendance rate during the educational sessions in each practice was high ; few problems were reported , and the physicians were perceived as being largely supportive of the recommendations we promoted , except for some scepticism regarding the use of thiazides as first-line antihypertensive medication . Multivariate regression models could explain only a small part of the observed variation across practice s and across trial- outcomes , and key factors that might explain the observed variation in adherence to the recommendations across practice s were not identified . Conclusion This study did not provide compelling explanations for the trial results . Possible reasons for this include a lack of statistical power and failure to include potential explanatory variables in our analyses , particularly organisational factors . More use of qualitative research methods in the course of the trial could have improved our underst and ing BACKGROUND Good blood pressure ( BP ) control reduces the risk of complications in people with type 2 diabetes , yet many do not achieve this . Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved , but the effect of such recommendations in routine primary care is unknown . AIM To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes . DESIGN OF STUDY A cluster r and omised controlled trial of 1534 patients with type 2 diabetes . SETTING Forty-two practice s in Nottingham , UK . METHOD Practice s were r and omised to continue usual care or to use a treatment algorithm design ed so that practice nurses and GPs would increase antihypertensive treatment in steps until the target of 140/80 mmHg was reached . Participants were assessed by a clinical interview and case note review at recruitment and at 1 year . The primary outcome measure was the proportion of participants achieving target BP at 1 year . RESULTS At 1 year there was no difference between the proportions of participants with well controlled BP in the intervention and control arms ( 36.6 % versus 34.3 % ; P = 0.27 ) . Mean systolic and diastolic blood pressures were identical in the two arms ( 143/78 mmHg ) . There was some evidence that participants in the intervention arm were more likely to be receiving higher doses of their antihypertensive drugs , although there was no significant difference in the number of different antihypertensive drugs prescribed . Participants in the intervention arm had a higher rate of primary care BP-related consultations over 12 months than those receiving usual care ( rate ratio = 1.55 , 95 % confidence interval [ CI ] = 1.26 to 1.88 , P<0.001 ) . CONCLUSION Despite increased monitoring and possibly higher doses of medication there was no improvement in blood pressure control . Improvements achieved by specialist nurse-led clinics in secondary care may not translate to people with type 2 diabetes in primary care setting Objectives : To evaluate the effect on the process of care of an active strategy to implement clinical guidelines on physiotherapy for low back pain . Design : A cluster r and omised controlled trial comparing an active strategy with st and ard dissemination . Setting : Primary care physiotherapy practice s. Participants : 113 physiotherapists were r and omly allocated to receive the guidelines by mail ( control group ) or to receive an additional active strategy ( intervention group ) which consisted of a multifaceted programme including education , discussion , role playing , feedback , and reminders . Main outcome measures : Adherence to the guidelines was measured by means of individual patients ’ forms recording the treatment completed by the physiotherapist . The forms were assessed using an algorithm based on the number of treatment sessions , treatment goals , interventions , and patient education . Results : Physiotherapists in the intervention group more often correctly limited the number of treatment sessions for patients with a normal course of back pain ( OR 2.39 ; 95 % CI 1.12 to 5.12 ) , more often set functional treatment goals ( OR 1.99 ; 95 % CI 1.06 to 3.72 ) , more often used mainly active interventions ( OR 2.79 ; 95 % CI 1.19 to 6.55 ) , and more often gave adequate patient education ( OR 3.59 ; 95 % CI 1.35 to 9.55 ) . They also adhered more to all four criteria ( OR 2.05 ; 95 % CI 1.15 to 3.65 ) . Conclusions : The active strategy moderately improved adherence to the guidelines . Active strategies are recommended to implement the clinical guidelines on physiotherapy for low back pain Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice . Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience . The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting . Methods A pragmatic cluster r and omised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis . Hospitals were r and omised to one of three interventions : st and ard dissemination ( SD ) of a guideline package , SD plus a web-based re source championed by an opinion leader , and SD plus plan-do- study -act ( PDSA ) . The primary outcome was duration of fluid fast prior to induction of anaesthesia . Secondary outcomes included duration of food fast , patients ’ experiences , and stakeholders ’ experiences of implementation , including influences . ANOVA was used to test differences over time and interventions . Results Nineteen acute NHS hospitals participated . Across timepoints , 3,505 duration of fasting observations were recorded . No significant effect of the interventions was observed for either fluid or food fasting times . The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone . The process evaluation showed different types of impact , including changes to practice s , policies , and attitudes . A rich picture of the implementation challenges emerged , including inter-professional tensions and a lack of clarity for decision-making authority and responsibility . Conclusions This was a large , complex study and one of the first national r and omised controlled trials conducted within acute care in implementation research . The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple ; however , implementation and practical challenges influenced the interventions ’ impact . A set of conditions for implementation emerges from the findings of this study , which are presented as theoretically transferable propositions that have international relevance .Trial registration IS RCT N18046709 - Peri-operative Implementation Study Evaluation ( POISE ) Abstract Objective To test a multifaceted collaborative quality improvement intervention design ed to promote evidence based surfactant treatment for preterm infants of 23 - 29 weeks ' gestation . Design Cluster r and omised controlled trial Setting and participants 114 neonatal intensive care units ( which treated 6039 infants of 23 - 29 weeks gestation born in 2001 ) . Main outcome measures Process of care measures : proportion of infants receiving first surfactant in the delivery room , proportion receiving first surfactant more than two hours after birth , and median time from birth to first dose of surfactant . Clinical outcomes : death before discharge home , and pneumothorax . Intervention Multifaceted collaborative quality improvement advice including audit and feedback , evidence review s , an interactive training workshop , and ongoing faculty support via conference calls and email . Results Compared with those in control hospitals , infants in intervention hospitals were more likely to receive surfactant in the delivery room ( adjusted odds ratio 5.38 ( 95 % confidence interval 2.84 to 10.20 ) ) , were less likely to receive the first dose more than two hours after birth ( adjusted odds ratio 0.35 ( 0.24 to 0.53 ) ) , and received the first dose of surfactant sooner after birth ( median of 21 minutes v 78 minutes , P < 0.001 ) . The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth . There were no significant differences in mortality or pneumothorax . Conclusion A multifaceted intervention including audit and feedback , evidence review s , quality improvement training , and follow up support changed the behaviour of health professionals and promoted evidence based practice Background In 2012 , in The Netherl and s a multidisciplinary practice guideline for the assessment and treatment of suicidal behavior was issued . The release of guidelines often fails to change professional behavior due to multiple barriers . Structured implementation may improve adherence to guidelines . This article describes the design of a study measuring the effect of an e-learning supported Train-the-Trainer program aim ing at the training of the full staff of departments in the application of the guideline . We hypothesize that both professionals and departments will benefit from the program . Method In a multicenter cluster r and omized controlled trial , 43 psychiatric departments spread over 10 regional mental health institutions throughout The Netherl and s will be clustered in pairs with respect to the most prevalent diagnostic category of patients and average duration of treatment . Pair members are r and omly allocated to either the experimental or the control condition . In the experimental condition , the full staff of departments , that is , all registered nurses , psychologists , physicians and psychiatrists ( n = 532 , 21 departments ) will be trained in the application of the guideline , in a one-day small interactive group Train-the-Trainer program . The program is supported by a 60-minute e-learning module with video vignettes of suicidal patients and additional instruction . In the control condition ( 22 departments , 404 professionals ) , the guideline shall be disseminated in the traditional way : through manuals , books , conferences , internet , review s and so on . The effectiveness of the program will be assessed at the level of both health care professionals and departments . Discussion We aim to demonstrate the effect of training of the full staff of departments with an e-learning supported Train-the-Trainer program in the application of a new clinical guideline . Strengths of the study are the natural setting , the training of full staff , the r and om allocation to the conditions , the large scale of the study and the willingness of both staff and management to participate in the study .Trial registration Dutch trial register : AIM To determine the impact and cost-effectiveness of telephone versus written access to magnetic resonance imaging ( MRI ) , and of different strategies for disseminating locally produced guidelines , upon requests by general practitioners ( GPs ) for knee and lumbar spine investigation . MATERIAL AND METHODS Two sequential pragmatic open cluster-r and omized trials were conducted within 39 general practice s. The outcome measure in each trial was concordance of request with local guidelines . Trial 1 : practice s requested MRI by telephone or in writing . Trial 2 : all practice s received guidelines , plus either : a practice -based seminar , practice -specific audit feedback , both seminar and feedback , or neither . RESULTS A total of 414 requests were assessed in the two trials . Trial 1 : telephone access cost pound4.86 more per request but rates of concordant requests were equivalent ( 65%/64 % : telephone/written ) . Trial 2 : compared to the control group , costs per practice were pound1911 higher in seminar group , pound1543 higher in feedback group and pound3578 higher for those receiving both . Concordance was greater following the intervention ( 74 % vs 65 % ; P < 0.05 ) , but there was no difference between the four study groups . CONCLUSIONS Method of access did not affect concordance . Written access was more cost-effective . Seminars and feedback were no more effective in modifying practice than guidelines alone , which was thus the most cost-effective option Background The underlying reasons for differences between clinical practice and systematic ally developed guidelines vary from one clinical problem to another . It is therefore logical to tailor strategies to support the implementation of guidelines to address identified barriers to change . The objective of this trial is to evaluate the effects of a tailored intervention to support the implementation of systematic ally developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease . Methods / Design Unblinded , cluster-r and omised trial . 150 general practice s will be recruited from two geographical areas in Norway , and r and omised to the intervention or control group ( passive dissemination of guidelines ) . Outcomes will be measured for all eligible patients seen in the participating practice s during one year after the intervention . A multifaceted intervention has been tailored to address identified barriers to change . Key components are an educational outreach visit with audit and feedback , and computerised reminders . Pharmacists will conduct the visits . During the outreach visit the main recommendations will be presented and software will be installed that links to the electronic medical record systems used in the participating practice s. The software will perform an audit that will be fed back during the visit , present pop-up reminders for patients with high blood pressure or cholesterol , and provide a cardiovascular risk calculator and patient education material . The main outcomes are the proportions of 1 ) first time prescriptions for hypertension where thiazides are not prescribed , 2 ) patients not assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs , and 3 ) patients treated for hypertension or high cholesterol for three months or more who have not achieved recommended treatment goals We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer ( CRC ) below age 50 or a second CRC below age 70 . Pathologists were asked to start microsatellite instability ( MSI ) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive . A multicentre cluster-r and omised controlled trial ( Clinical Trials.gov , number NCT00141466 ) was performed in 12 pathology laboratories ( clusters ) , serving 29 community hospitals . All received an introduction to the new guideline . In the intervention group , surgeons received education and tumour test result reminders ; pathologists were provided with inclusion criteria cards , an electronic patient inclusion reminder system and feedback on inclusion . Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome . The actual recognition was 18 % more successful in the intervention as compared to the control arm ( 77 % ( 120 of 156 ) compared to 59 % ( 65 of 110 ) ) , with an adjusted odds ratio ( OR ) = 2.8 ( 95 % confidence interval ( CI ) 1.1–7.0 ) . The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients , OR = 4.2 ( 95 % CI 1.7–10.1 ) . An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome OBJECTIVE To test an interdisciplinary , multifaceted , translating research into practice ( TRIP ) intervention to ( a ) promote adoption , by physicians and nurses , of evidence -based ( EB ) acute pain management practice s in hospitalized older adults , ( b ) decrease barriers to use of EB acute pain management practice s , and ( c ) decrease pain intensity of older hospitalized adults . STUDY DESIGN Experimental design with the hospital as the unit of r and omization . STUDY SETTING Twelve acute care hospitals in the Midwest . DATA SOURCES ( a ) Medical records ( MRs ) of patients > or = 65 years or older with a hip fracture admitted before and following implementation of the TRIP intervention and ( b ) physicians and nurses who care for those patients . DATA COLLECTION Data were abstract ed from MRs and questions distributed to nurses and physicians . PRINCIPAL FINDINGS The Summative Index for Quality of Acute Pain Care ( 0 - 18 scale ) was significantly higher for the experimental ( 10.1 ) than comparison group ( 8.4 ) at the end of the TRIP implementation phase . At the end of the TRIP implementation phase , patients in the experimental group had a lower mean pain intensity rating than those in the comparison group ( p<.0001 ) . CONCLUSION The TRIP intervention improved quality of acute pain management of older adults hospitalized with a hip fracture Background There is increasing evidence that clinical guidelines can lead to improvements in clinical care . However , they are not self-implementing . While educational outreach visits may improve prescribing behaviour , the effectiveness of routine delivery of these visits by existing pharmaceutical advisers is unknown . Methods Within a pragmatic r and omized controlled trial , involving all general practice s in two primary care trusts ( PCTs ) , routine methods were used to distribute guidelines for the choice of antidepressants for the management of depression . Intervention practice s were offered two visits ( most accepted only one ) by their PCT pharmaceutical adviser who had been trained in the techniques of outreach visiting . Intervention practice s were visited regardless of whether they had prior problems with prescribing ( ' untargeted ' visits ) . The intervention was evaluated using level three prescribing analysis and cost ( PACT ) data for antidepressant drugs for the six months during which the intervention was delivered and the subsequent twelve months . Results Across the 72 study practice s there was no significant impact of the intervention on usage of any group of antidepressant drugs . Conclusion The routine use of untargeted educational outreach visiting delivered by existing pharmaceutical advisers may not be a worthwhile strategy .Trial registration Clinical Trials.gov OBJECTIVE To measure the impact of a computerized guideline for glucose regulation in an ICU . DESIGN A r and omized , controlled trial with an off-on-off design . METHODS We implemented a glucose regulation guideline in an intensive care unit in paper form during the first study period . During the second period , the guideline was r and omly applied in either paper or computerized form . In the third period , the guideline was available only in paper form . MEASUREMENTS AND RESULTS We analyzed data for 484 patients . During the intervention period , the control group included 54 patients and the computerized intervention group included 66 patients . The two guideline -related outcome measures consisted of compliance with : ( a ) glucose measurement timing recommendations and ( b ) insulin dose advice . We measured clinical impact as the proportion of time that glucose levels fell within target range . In the first ( paper-based ) study period , 29.0 % of sample s occurred with optimal timing ; during the second period , this increased to 35.5 % for paper-based and to 40.2 % for computerized protocol s. The third study period timeliness scores reverted to the first period rates . Late ( suboptimal ) sampling occurred for 66 % of glucose measurements in the first study period , for 42 % of paper-based and 28 % of computer-based protocol sample s in the second period , and for 50.0 % of sample s in the third study period . In the first study period , insulin-dosing guideline compliance was 56.3 % ; in the second period , it was 64.2 % for paper-based and 77.3 % for computer-based protocol s , and it fell to 42.4 % in the third period . For the second study period , the time that a patient 's glucose values fell within target range improved for both the control ( 52.9 % ) and the computerized groups ( 54.2 % ) compared with the first study period ( 44.3 % ) and the third period ( 42.3 % ) . CONCLUSION Implementing a computerized version of a guideline significantly improved timeliness of measurements and glucose level regulation for critically ill patients compared with implementing a paper-based version of the guideline BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue Abstract Objective : To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat Design : Unblinded , cluster r and omised pretest-post-test trial Setting : 142 general practice s in Norway Participants : 72 practice s received interventions to implement guidelines for urinary tract infection and 70 practice s received interventions to implement guidelines for sore throat , serving as controls for each other . 59 practice s in the urinary tract infection group and 61 practice s in the sore throat group completed the study . Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection . Interventions : Interventions were developed to overcome identified barriers to implementing the guidelines . The main components of the tailored interventions were patient educational material , computer based decision support and reminders , an increase in the fee for telephone consultations , and interactive courses for general practitioners and practice assistants Main outcome measures : Changes in rates of use of antibiotics , laboratory tests , and telephone consultations Results : Patients in the sore throat group were 3 % less likely to receive antibiotics after the intervention . Women with symptoms of urinary tract infection in the intervention group were 5.1 % less likely to have a laboratory test ordered . No significant differences were found between the groups for the other outcomes . Large variation was found across the included practice sin the rates of antibiotic prescription , use of laboratory tests and telephone consultations , and in the extent of change for all three outcome measures Conclusions : Passively delivered , complex interventions targeted at identified barriers to change had little effect in changing Background A gap exists between evidence and practice regarding the management of cardiovascular risk factors . This gap could be narrowed if systematic ally developed clinical practice guidelines were effectively implemented in clinical practice . We evaluated the effects of a tailored intervention to support the implementation of systematic ally developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease . Methods and Findings We conducted a cluster-r and omized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practice s in two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders linked to the medical record system . Pharmacists conducted the visits . Outcomes were measured for all eligible patients seen in the participating practice s during 1 y before and after the intervention . The main outcomes were the proportions of ( 1 ) first-time prescriptions for hypertension where thiazides were prescribed , ( 2 ) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs , and ( 3 ) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals . The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug . Thiazides were prescribed to 17 % of patients in the intervention group versus 11 % in the control group ( relative risk 1.94 ; 95 % confidence interval 1.49–2.49 , adjusted for baseline differences and clustering effect ) . Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals . Conclusions Our tailored intervention had a significant impact on prescribing of antihypertensive drugs , but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care Background Mild head injuries commonly present to emergency departments . The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury , and which patients can safely be sent home . Traumatic brain injuries may exist with subtle symptoms or signs , but can still lead to adverse outcomes . Despite the existence of several high quality clinical practice guidelines , internationally and in Australia , research shows inconsistent implementation of these recommendations . The aim of this trial is to test the effectiveness of a targeted , theory- and evidence -informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients ( 18 years of age or older ) who present following mild head injuries ( concussion ) , compared with passive dissemination of these recommendations . The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed . Methods / design The design of this study is a cluster r and omised trial . We aim to include 34 Australian 24-hour emergency departments , which will be r and omised to an intervention or control group . Control group departments will receive a copy of the most recent Australian evidence -based clinical practice guideline on the acute management of patients with mild head injuries . The intervention group will receive an implementation intervention based on an analysis of influencing factors , which include local stakeholder meetings , identification of nursing and medical opinion leaders in each site , a train-the-trainer day and st and ardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time . Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery ( patient level outcomes ) . In consenting hospitals , eligible patients will be recruited for a follow-up telephone interview conducted by trained research ers . A cost-effectiveness analysis and process evaluation using mixed- methods will be conducted . Sample size calculations are based on including 30 patients on average per department . Outcome assessors will be blinded to group allocation . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12612001286831 ( date registered 12 December 2012 ) BACKGROUND Educational outreach visits , particularly when combined with social marketing , appear to be a promising approach to modifying health professional behaviour , especially prescribing . Results from previous studies have shown a varying effect . OBJECTIVE The purpose of the study is to examine the effect of academic detailing as a method of implementing a clinical guideline in general practice . METHODS A cluster r and omized , controlled , blinded study was carried out of the effect of an academic detail visit compared with postal distribution of a guideline for prescribing asthma medication . Half the practice s in a Danish county with 100 practice s were visited once . The outcome measure was routinely collected data from all Danish pharmacies on the sales of asthma medication . Data were collected monthly for 2 years before to 1 year after the intervention . RESULTS There was no effect on the pattern of prescription of asthma medicines following the visit , neither immediately nor long term . CONCLUSION We found no effect of academic detailing as a single intervention Objectives . This project aim ed to compare the independent and combined effectiveness of two implementation interventions of guidelines for ordering thyroid function tests : a Memor and um Pocket Card ( MPC ) and a Test Request Form ( TRF ) . Research Design . Intervention groups were wards . The study used an experimental 2 * 2 factorial design with matching hospitals according to size and activity and wards according to preintervention appropriateness for test ordering . Four ward groups were established : the dual intervention group , the order form group , the pocket card group and the control group . Physicians in all groups received guidelines and were invited to a local information meeting . Measures . The main outcome measure of effectiveness was the Guideline Conformity Rate ( GCR ) . Results . Six hospitals participated in the study ( two middle-sized hospitals , two small-sized hospitals and two psychiatric hospitals ) . A total of 1412 orders for thyroid function tests were collected . GCR was 78 % in the dual intervention group , 83 % in the order form group , 73 % in the pocket card group and 62 % in the control group . The interaction between TRF and MPC was not significant ( & bgr ; = −0.70;P = 0.21 ) . Compared with simple information , TRF was effective in increasing GCR ( OR , 2.65 ; 95 % CI , 1.52–4.62 ) , unlike MPC ( OR , 1.28 ; CI , 0.75–2.19 ) . Conclusions . Using a robust design , our study shows the greater effectiveness of TRF than MPC and their association in implementing thyroid function test guidelines OBJECTIVE To determine the impact of a multifaceted knowledge translation strategy for a new vaccination pain management guideline on public health immunizers ' attitudes , beliefs and use of pain-relieving strategies during childhood vaccination . METHOD Using a r and omized controlled pre-post study design , public health nurses ( PHNs ) at intervention sites received a multifaceted knowledge translation intervention about new pain management guidelines incorporated in the British Columbia Immunization Program Manual , including education , supplies and online support . Attitudes and beliefs of PHNs toward immunization pain and pain management , and use of pain-relieving strategies were compared for the intervention sites between the pre- and postimplementation phases . RESULTS A total of 516 children were immunized by 31 PHNs pre- and postimplementation in the intervention sites . Postimplementation , satisfaction and confidence with ability to manage pain and willingness to use newly recommended strategies were significantly more positive ( P<0.05 ) in the intervention sites , and overall use of at least one newly recommended strategy increased from 49.8 % preintervention to 77.6 % postimplementation ( P<0.001 ) . CONCLUSION The knowledge translation intervention improved PHN immunizers ' attitudes , beliefs and practice s regarding paediatric vaccination pain management . Reducing pain may result in a better immunization experience for children , caregivers and immunizers Objective : To evaluate the effect on antibiotic prescribing of an intervention in existing local quality circles promoting an evidence -based guideline for acute rhinosinusitis . Design : A pragmatic cluster-r and omised controlled trial comparing st and ard dissemination of the guideline by mail with an additional strategy using quality circles . Setting : General practice in Fl and ers , Belgium . Participants : General practitioners ( GPs ) in 18 local quality circles were r and omly allocated to two study arms . All GPs received the guideline by mail . GPs in the nine quality circles allocated to the intervention arm received an additional group intervention , which consisted of one self-led meeting using material introduced to the group moderator by a member of the research team . Main outcome measures : Adherence to the guideline was measured as differences in the proportion of antibiotic prescriptions , including the choice of antibiotic , between the two study arms after the intervention period . GPs registered their encounters with patients presenting with signs and symptoms of acute rhinosinusitis in a booklet design ed for the study . Results : A total of 75 doctors ( 29 % of GPs in the participating quality circles ) registered 408 consultations . In the intervention group , 56.9 % of patients received an antibiotic compared with 58.3 % in the control group . First-choice antibiotics were issued in 34.5 % of antibiotic prescriptions in the intervention group compared with 29.4 % in the control group . After adjusting for patient and GP characteristics , the ORadj for antibiotics prescribed in the intervention arm compared with the control arm was 0.63 ( 95 % CI 0.29 to 1.37 ) . There was no effect on the choice of antibiotic ( ORadj 1.07 , 95 % CI 0.34 to 3.37 ) . Conclusion : A single intervention in quality circles of GPs integrated in the group ’s normal working procedure did not have a significant effect on the quality of antibiotic prescribing . More attention to the context and structure of primary care practice , and insight into the process of self-reflective learning may provide clues to optimise the effectiveness of quality circles BACKGROUND Various methods are available for implementing change in the clinical behaviour of general practitioners ( GPs ) . Although passive dissemination of information is generally ineffective , other methods can be variably effective . Few studies have investigated the impact of tailored methods . AIM To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs . DESIGN OF STUDY R and omised controlled trial . SETTING Sixty general practice s in Engl and ; 30 GPs in the control group , 34 in the intervention group . METHOD Practitioners identified patients presenting with depression before and after the implementation of guidelines ( control group n = 192 in the first data collection , n = 181 in the second ; intervention group n = 210 in the first data collection and n = 197 in the second ) . The main outcome measures were : record of adherence to guideline recommendations in clinical records ; proportion of patients with Beck Depression Inventory ( BDI ) score less than 11 at 16 weeks after diagnosis . RESULTS In comparison with the control group , in the group of GPs receiving tailored implementation , there were increases in the proportions of patients assessed for suicide risk . In the intervention group , the proportion of patients with BDI scores of less than 11 at 16 weeks increased . CONCLUSION Obstacles to implementation can be identified and strategies tailored to address them . The findings indicate a new approach for research to underst and and develop methods of implementation BACKGROUND R and omized studies examining the effect of training of mental health professionals in suicide prevention guidelines are scarce . We assessed whether professionals benefited from an e-learning supported Train-the-Trainer programme aim ed at the application of the Dutch multidisciplinary suicide prevention guideline . METHODS 45 psychiatric departments from all over the Netherl and s were clustered in pairs and r and omized . In the experimental condition , all of the staff of psychiatric departments was trained by peers with an e-learning supported Train-the-Trainer programme . Guideline adherence of individual professionals was measured by means of the response to on-line video fragments . Multilevel analyses were used to establish whether variation between conditions was due to differences between individual professionals or departments . RESULTS Multilevel analysis showed that the intervention result ed in an improvement of individual professionals . At the 3 month follow-up , professionals who received the intervention showed greater guideline adherence , improved self-perceived knowledge and improved confidence as providers of care than professionals who were only exposed to traditional guideline dissemination . Subgroup analyses showed that improved guideline adherence was found among nurses but not among psychiatrists and psychologists . No significant effect of the intervention on team performance was found . LIMITATIONS The ICT environment in departments was often technically inadequate when displaying the video clips clip of the survey . This may have caused considerable drop-out and possibly introduced selection bias , as professionals who were strongly affiliated to the theme of the study might have been more likely to finish the study . CONCLUSIONS Our results support the idea that an e-learning supported Train-the-Trainer programme is an effective strategy for implementing clinical guidelines and improving care for suicidal patients . TRIAL REGISTRATION Netherl and s Trial Register ( NTR3092 www.trialregister.nl ) PURPOSE Patients with pneumonia often remain hospitalized after they are stable clinical ly , and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge . The purpose of this study was to determine whether implementation of an evidence -based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia . METHODS In a seven-site , cluster r and omized clinical trial , we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups . Within site , physician groups were assigned r and omly to receive a practice guideline alone ( control arm ) or a practice guideline that was implemented using a multifaceted strategy ( intervention arm ) . The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay ; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models . Medical outcomes were assessed at 30 days . RESULTS Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group ( hazard ratio [ HR ] = 1.23 ; 95 % confidence interval [ CI ] : 1.00 to 1.52 ; P = 0.06 ) than in the control group . Intervention patients were discharged more quickly , but the difference was not statistically significant ( HR = 1.16 ; 95 % CI : 0.97 to 1.38 ; P = 0.11 ) . Fewer intervention ( 55 % [ 157/283 ] ) than control ( 63 % [ 206/325 ] ) patients had medical complications during the index hospitalization ( P = 0.04 ) , with no differences in other medical outcomes , including mortality , rehospitalization , and return to usual activities , between treatment arms . CONCLUSIONS The multifaceted guideline implementation strategy result ed in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay , without affecting patient outcomes Background The gap between the level of care recommended by evidence -based clinical practice guidelines and the actual care delivered to patients in practice has been well established . The Canadian Diabetes Association ( CDA ) created an implementation strategy to improve the implementation of its 2008 guidelines . This study will evaluate the impact of the strategy to improve cardiovascular disease ( CVD ) screening , prevention and treatment for people with diabetes . Design A pragmatic cluster-r and omized trial will be conducted to evaluate the CDA 's CVD Toolkit . All family physicians in Ontario , Canada were r and omly allocated to receive the Toolkit , which includes several printed educational material s targeting CVD screening , prevention and treatment , either in spring 2009 ( intervention arm ) or in spring 2010 ( control arm ) . R and omization occurred at the level of the practice . Forty family physicians from each arm will be recruited to participate , and the medical records for 20 of their diabetic patients at high risk for CVD will be retrospectively review ed . Outcome measures will be assessed for each patient between July 2009 and March 2010 . The primary outcome will be that the patient is receiving a statin . Secondary outcomes will include 1 ) the receipt of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker , 2 ) various intermediate measures ( A1c , blood pressure , LDL-cholesterol , total-/HDL-cholesterol ratio , body mass index and waist circumference ) , and 3 ) clinical inertia ( the failure to change therapy in response to an abnormal A1c , blood pressure or cholesterol reading ) . The analysis will be carried out using multilevel hierarchical logistic regression models to account for the clustered nature of the data . The group assignment will be a physician-level variable . In addition , a process evaluation study with six focus groups of family physicians will assess the acceptability of the CDA 's Toolkit and will explore factors contributing to any change or lack of change in behaviour , from the perspectives of family physicians . Discussion Printed educational material s for physicians have been shown to exert small-to-moderate changes in patient care . The CDA 's CVD Toolkit is an example of a practice guideline implementation strategy that can be disseminated to a wide audience relatively inexpensively , and so demonstrating its effectiveness at improving diabetes care could have important consequences for guideline developers , policy makers and clinicians . Trial Registration The trial is registered with http://www . clinical trials.gov , ID # In a pragmatic cluster-r and omized trial , Baiju Shah and colleagues evaluated the effectiveness of printed educational material s for clinician education focusing on cardiovascular disease screening and risk reduction in people with diabetes . Please see later in the article for the Editors ' Background One-half of patients with cancer have pain . In nearly one out of two cancer patients with pain , this was undertreated . Inadequate pain control still remains an important problem in this group of patients . Therefore , in 2008 a national , evidence -based multidisciplinary clinical practice guideline ' pain in patients with cancer ' has been developed . Yet , publishing a guideline is not enough . Implementation is needed to improve pain management . An innovative implementation strategy , Short Message Service with Interactive Voice Response ( SVS-IVR ) , has been developed and pilot tested . This study aims to evaluate on effectiveness of this strategy to improve pain reporting , pain measurement and adequate pain therapy . In addition , whether the active role of the patient and involvement of caregivers in pain management may change . Methods / design A cluster r and omised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherl and s , with three hospitals in the intervention and three in the control condition . Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention . The intervention includes training of professionals ( medical oncologists , nurses , and general practitioners ) and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients , pain management by medical oncologists , nurses , and general practitioners , and decrease pain intensity . Discussion This innovative implementation strategy with technical tools and the involvement of patients , may enhance the use of the guideline ' pain in patients with cancer ' for pain management . Short Message Service alerts may serve as a tool to support self-management of patients . Therefore , the SMS-IVR intervention may increase the feeling of having control over one 's life . Trail registration Netherl and s Trial Register ( NTR ) : |
538 | 27,744,168 | CBT effects compared to active controls were mixed ( EQ1 ) .
SSRI/SNRI were more effective than placebo ( EQ1 ) but comparative effectiveness remains uncertain .
RCTs of web/computer-based interventions showed mixed results ( EQ1 ) .
CBM/ABM was not more efficacious than active controls ( EQ1 ) .
High quality RCTs support treatment with CBT and medication . | Three questions were addressed : ( i ) Is the treatment more effective than passive controls ? (
ii ) Is there evidence that the treatment is superior to or non-inferior to ( i.e. , as good as ) active controls ? (
iii ) What is the quality of evidence for the treatment ? | BACKGROUND Various studies find relationships among anxiety and depressive disorders of adolescence and adulthood . This study prospect ively examines the magnitude of longitudinal associations between adolescent and adult anxiety or depressive disorders . METHODS An epidemiologically selected sample of 776 young people living in upstate New York received DSM-based psychiatric assessment s in 1983 , 1985 , and 1992 using structured interviews . The magnitude of the association between adolescent and adult anxiety or depressive disorders was quantified using odds ratios generated from logistic regression analyses and from a set of latent Markov analyses . We focus on longitudinal associations among narrowly defined DSM anxiety or depressive disorders . RESULTS In simple logistic models , adolescent anxiety or depressive disorders predicted an approximate 2- to 3-fold increased risk for adulthood anxiety or depressive disorders . There was evidence of specificity in the course of simple and social phobia but less specificity in the course of other disorders . Results from the analyses using latent variables suggested that while most adolescent disorders were no longer present in young adulthood , most adult disorders were preceded by adolescent disorders . CONCLUSIONS An anxiety or depressive disorder during adolescence confers a strong risk for recurrent anxiety or depressive disorders during early adulthood . Most anxiety and depressive disorders in young adults may be preceded by anxiety or depression in adolescence OBJECTIVE The goal of this study was to examine the associations between specific anxiety disorders and the risk of major depressive disorder and to explore the role of various clinical characteristics of anxiety disorders in these relationships using a prospect i ve , longitudinal design . METHOD The data are from a 4-year prospect i ve , longitudinal community study , which included both baseline and follow-up survey data on 2548 adolescents and young adults aged 14 to 24 years at baseline . DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview . RESULTS The presence at baseline of any anxiety disorder ( odds ratio [ OR ] = 2.2 [ 95 % CI = 1.6 to 3.2 ] ) and each of the anxiety disorders ( specific phobia , OR = 1.9 [ 95 % CI = 1.3 to 2.8 ] ; social phobia , OR = 2.9 [ 95 % CI = 1.7 to 4.8 ] ; agoraphobia , OR = 3.1 [ 95 % CI = 1.4 to 6.7 ] ; panic disorder , OR = 3.4 [ 95 % CI = 1.2 to 9.0 ] ; generalized anxiety disorder , OR = 4.5 [ 95 % CI = 1.9 to 10.3 ] ) was associated with a significantly ( p < .05 ) increased risk of first onset of major depressive disorder . These associations remained significant after we adjusted for mental disorders occurring prior to the onset of the anxiety disorder , with the exception of the panic disorder association . The following clinical characteristics of anxiety disorders were associated with a significantly ( p < .05 ) increased risk of developing major depressive disorder : more than 1 anxiety disorder , severe impairment due to the anxiety disorder , and comorbid panic attacks . In the final model , which included all clinical characteristics , severe impairment remained the only clinical characteristic that was an independent predictor of the development of major depressive disorder ( OR = 2.2 [ 95 % CI = 1.0 to 4.4 ] ) . CONCLUSION Our findings suggest that anxiety disorders are risk factors for the first onset of major depressive disorder . Although a number of clinical characteristics of anxiety disorders appear to play a role in the association between anxiety disorders and depression , severe impairment is the strongest predictor of major depressive disorder OBJECTIVE This study evaluated follow-up outcomes associated with cognitive behavioral therapy ( CBT ) for childhood anxiety by comparing successfully and unsuccessfully treated participants 6.72 to 19.17 years after treatment . METHOD Participants were a sample of 66 youths ( ages 7 - 14 years at time of treatment , ages 18 - 32 years at present follow-up ) who had been diagnosed with an anxiety disorder and r and omized to treatment in a r and omized clinical trial on average 16.24 ( SD = 3.56 , range = 6.72 - 19.17 ) years prior . The present follow-up included self-report measures and a diagnostic interview to assess anxiety , depression , and substance misuse . RESULTS Compared with those who responded successfully to CBT for an anxiety disorder in childhood , those who were less responsive had higher rates of panic disorder , alcohol dependence , and drug abuse in adulthood . Relative to a normative comparison group , those who were less responsive to CBT in childhood had higher rates of several anxiety disorders and substance misuse problems in adulthood . Participants remained at particularly increased risk , relative to the normative group , for generalized anxiety disorder and nicotine dependence regardless of initial treatment outcome . CONCLUSIONS The present study is the first to assess the long-term follow-up effects of CBT treatment for an anxiety disorder in youth on anxiety , depression , and substance abuse through the period of young adulthood when these disorders are often seen . Results support the presence of important long-term benefits of successful early CBT for anxiety OBJECTIVE We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study ( CAMS ) . METHOD CAMS youth ( N = 488 ; 74 % ≤ 12 years of age ) with DSM-IV separation , generalized , or social anxiety disorder were r and omized to 12 weeks of cognitive-behavioral therapy ( CBT ) , sertraline ( SRT ) , CBT+SRT ( COMB ) , or medication management/pill placebo ( PBO ) . Responders attended 6 monthly booster sessions in their assigned treatment arm ; youth in COMB and SRT continued on their medication throughout this period . Efficacy of COMB , SRT , and CBT ( n = 412 ) was assessed at 24 and 36 weeks postr and omization . Youth r and omized to PBO ( n = 76 ) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here . Independent evaluators blind to study condition assessed anxiety severity , functioning , and treatment response . Concomitant treatments were allowed but monitored over follow-up . RESULTS The majority ( > 80 % ) of acute responders maintained positive response at both weeks 24 and 36 . Consistent with acute outcomes , COMB maintained advantage over CBT and SRT , which did not differ , on dimensional outcomes ; the 3 treatments did not differ on most categorical outcomes over follow-up . Compared to COMB and CBT , youth in SRT obtained more concomitant psychosocial treatments , whereas those in SRT and CBT obtained more concomitant combined ( medication plus psychosocial ) treatment . CONCLUSIONS COMB maintained advantage over CBT and SRT on some measures over follow-up , whereas the 2 monotherapies remained indistinguishable . The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies , although other explanations are possible . Although outcomes were variable , most CAMS-treated youth experienced sustained treatment benefit . Clinical trial registration information-Child and Adolescent Anxiety Disorders ( CAMS ) ; URL : http:// clinical trials.gov . Unique identifier : NCT00052078 BACKGROUND Anxiety disorders are common psychiatric conditions affecting children and adolescents . Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders , little is known about their relative or combined efficacy . METHODS In this r and omized , controlled trial , we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder , generalized anxiety disorder , or social phobia to receive 14 sessions of cognitive behavioral therapy , sertraline ( at a dose of up to 200 mg per day ) , a combination of sertraline and cognitive behavioral therapy , or a placebo drug for 12 weeks in a 2:2:2:1 ratio . We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4 , 8 , and 12 . RESULTS The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7 % for combination therapy ( P<0.001 ) , 59.7 % for cognitive behavioral therapy ( P<0.001 ) , and 54.9 % for sertraline ( P<0.001 ) ; all therapies were superior to placebo ( 23.7 % ) . Combination therapy was superior to both monotherapies ( P<0.001 ) . Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response ; combination therapy had a greater response than cognitive behavioral therapy , which was equivalent to sertraline , and all therapies were superior to placebo . Adverse events , including suicidal and homicidal ideation , were no more frequent in the sertraline group than in the placebo group . No child attempted suicide . There was less insomnia , fatigue , sedation , and restlessness associated with cognitive behavioral therapy than with sertraline . CONCLUSIONS Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders ; a combination of the two therapies had a superior response rate . ( Clinical Trials.gov number , NCT00052078 . BACKGROUND If most adults with mental disorders are found to have a juvenile psychiatric history , this would shift etiologic research and prevention policy to focus more on childhood mental disorders . METHOD Our prospect i ve longitudinal study followed up a representative birth cohort ( N = 1037 ) . We made psychiatric diagnoses according to DSM criteria at 11 , 13 , 15 , 18 , 21 , and 26 years of age . Adult disorders were defined in the following 3 ways : ( 1 ) cases diagnosed using a st and ardized diagnostic interview , ( 2 ) the subset using treatment , and ( 3 ) the subset receiving intensive mental health services . Follow-back analyses ascertained the proportion of adult cases who had juvenile diagnoses and the types of juvenile diagnoses they had . RESULTS Among adult cases defined via the Diagnostic Interview Schedule , 73.9 % had received a diagnosis before 18 years of age and 50.0 % before 15 years of age . Among treatment-using cases , 76.5 % received a diagnosis before 18 years of age and 57.5 % before 15 years of age . Among cases receiving intensive mental health services , 77.9 % received a diagnosis before 18 years of age and 60.3 % before 15 years of age . Adult disorders were generally preceded by their juvenile counterparts ( eg , adult anxiety was preceded by juvenile anxiety ) , but also by different disorders . Specifically , adult anxiety and schizophreniform disorders were preceded by a broad array of juvenile disorders . For all adult disorders , 25 % to 60 % of cases had a history of conduct and /or oppositional defiant disorder . CONCLUSIONS Most adult disorders should be reframed as extensions of juvenile disorders . In particular , juvenile conduct disorder is a priority prevention target for reducing psychiatric disorder in the adult population |
539 | 32,181,812 | We found that there is significant variation in scribe expectations and responsibilities across healthcare organizations ; scribes also frequently adapt their work based on the provider 's style and preferences .
Further , scribes ' job extends far beyond capturing conversation in the exam room ; they also actively interact with patients and the care team and integrate data from other sources such as prior charts and lab test results .
First , a one-size-fits-all solution will be unlikely to work because of the significant variation in scribe work .
Finally , issues of patient consent and privacy have yet to be adequately addressed , which could become paramount barriers to implementing such technologies in realistic clinical setting s. CONCLUSIONS Medical scribes perform complex and delicate work . | OBJECTIVE Use of medical scribes reduces clinician burnout by sharing the burden of clinical documentation .
However , medical scribes are cost-prohibitive for most setting s , prompting a growing interest in developing ambient , speech-based technologies capable of automatically generating clinical documentation based on patient-provider conversation .
Through a systematic review , we aim ed to develop a thorough underst and ing of the work performed by medical scribes in order to inform the design of such technologies . | Introduction Physicians dedicate substantial time to documentation . Scribes are sometimes used to improve efficiency by performing documentation tasks , although their impacts have not been prospect ively evaluated . Our objective was to assess a scribe program ’s impact on emergency department ( ED ) throughput , physician time utilization , and job satisfaction in a large academic emergency medicine practice . Methods We evaluated the intervention using pre- and post-intervention surveys and administrative data . All site physicians were included . Pre- and post-intervention data were collected in four-month periods one year apart . Primary outcomes included changes in monthly average ED length of stay ( LOS ) , provider-specific average relative value units ( RVUs ) per hour ( raw and normalized to volume ) , self-reported estimates of time spent teaching , self-reported estimates of time spent documenting , and job satisfaction . We analyzed data using descriptive statistics and appropriate tests for paired pre-post differences in continuous , categorical , and ranked variables . Results Pre- and post-survey response rates were 76.1 % and 69.0 % , respectively . Most responded positively to the intervention , although 9.5 % reported negative impressions . There was a 36 % reduction ( 25%–50 % ; p<0.01 ) in time spent documenting and a 30 % increase ( 11%–46 % , p<0.01 ) in time spent in direct patient contact . No statistically significant changes were seen in job satisfaction or perception of time spent teaching . ED volume increased by 88 patients per day ( 32–146 , p=0.04 ) pre- to post- and LOS was unchanged ; rates of patients leaving against medical advice dropped , and rates of patients leaving without being seen increased . RVUs per hour increased 5.5 % and per patient 5.3 % ; both were statistically significant . No statistically significant changes were seen in patients seen per hour . There was moderate correlation between changes in ED volume and changes in productivity metrics . Conclusion Scribes were well received in our practice . Documentation time was substantially reduced and redirected primarily to patient care . Despite an ED volume increase , LOS was maintained , with fewer patients leaving against medical advice but more leaving without being seen . RVUs per hour and per patient both increased PURPOSE Scribes are increasingly being used in clinical practice despite a lack of high- quality evidence regarding their effects . Our objective was to evaluate the effect of medical scribes on physician satisfaction , patient satisfaction , and charting efficiency . METHODS We conducted a r and omized controlled trial in which physicians in an academic family medicine clinic were r and omized to 1 week with a scribe then 1 week without a scribe for the course of 1 year . Scribes drafted all relevant documentation , which was review ed by the physician before attestation and signing . In encounters without a scribe , the physician performed all charting duties . Our outcomes were physician satisfaction , measured by a 5-item instrument that included physicians ’ perceptions of chart quality and chart accuracy ; patient satisfaction , measured by a 6-item instrument ; and charting efficiency , measured by time to chart close . RESULTS Scribes improved all aspects of physician satisfaction , including overall satisfaction with clinic ( OR = 10.75 ) , having enough face time with patients ( OR = 3.71 ) , time spent charting ( OR = 86.09 ) , chart quality ( OR = 7.25 ) , and chart accuracy ( OR = 4.61 ) ( all P values < .001 ) . Scribes had no effect on patient satisfaction . Scribes increased the proportion of charts that were closed within 48 hours ( OR = 1.18 , P = .028 ) . CONCLUSIONS To our knowledge , we have conducted the first r and omized controlled trial of scribes . We found that scribes produced significant improvements in overall physician satisfaction , satisfaction with chart quality and accuracy , and charting efficiency without detracting from patient satisfaction . Scribes appear to be a promising strategy to improve health care efficiency and reduce physician burnout PURPOSE The increasing use of electronic medical records during the clinical encounter brings not only benefits but also barriers that may affect the doctor-patient relationship and increase the work burden of the physician . We evaluated whether the use of an electronic medical record scribe in an academic urology program would ameliorate these problems . MATERIAL S AND METHODS We r and omly assigned electronic medical record scribes to the office hours of 5 academic urologists , and using surveys we evaluated patient and physician acceptance and satisfaction . RESULTS Patients were accepting of an electronic medical record scribe and satisfaction rates were high ( 93 % vs 87 % in the absence of a scribe , p = 0.36 ) . Patients were comfortable disclosing urological information in the presence of the scribe . Physicians were dramatically more satisfied with office hours when a scribe was present ( 69 % vs 19 % , p < 0.001 ) . We were unable to determine whether the presence of a scribe improves productivity . CONCLUSIONS Electronic medical record scribes in a urology practice may be a practical solution to provide documentation while maintaining or improving the doctor-patient relationship because they increase physician satisfaction and do not detract from patient satisfaction Background Use of electronic health records ( EHRs ) is associated with physician stress and burnout . While emergency departments and subspecialists have used scribes to address this issue , little is known about the impact of scribes in academic primary care . Objective Assess the impact of a scribe on physician and patient satisfaction at an academic general internal medicine ( GIM ) clinic . Design Prospect i ve , pre-post-pilot study . During the 3-month pilot , physicians had clinic sessions with and without a scribe . We assessed changes in ( 1 ) physician workplace satisfaction and burnout , ( 2 ) time spent on EHR documentation , and ( 3 ) patient satisfaction . Participants Six GIM faculty and a convenience sample of their patients ( N = 325 ) at an academic GIM clinic . Main Measures A 21-item pre- and 44-item post-pilot survey assessed physician workplace satisfaction and burnout . Physicians used logs to record time spent on EHR documentation outside of clinic hours . A 27-item post-visit survey assessed patient satisfaction during visits with and without the scribe . Key Results Of six physicians , 100 % were satisfied with clinic workflow post-pilot ( vs. 33 % pre-pilot ) , and 83 % were satisfied with EHR use post-pilot ( vs. 17 % pre-pilot ) . Physician burnout was low at baseline and did not change post-pilot . Mean time spent on post-clinic EHR documentation decreased from 1.65 to 0.76 h per clinic session ( p = 0.02 ) . Patient satisfaction was not different between patients who had clinic visits with vs. without scribe overall or by age , gender , and race . Compared to patients 65 years or older , younger patients were more likely to report that the physician was more attentive and provided more education during visits with the scribe present ( p = 0.03 and 0.02 , respectively ) . Male patients were more likely to report that they disliked having a scribe ( p = 0.03 ) . Conclusion In an academic GIM setting , employment of a scribe was associated with improved physician satisfaction without compromising patient satisfaction Objective Scribes have been used in the emergency department to improve physician productivity and patient interaction . There are no controlled , prospect i ve studies of scribe use in the clinic setting . Methods A prospect i ve controlled study compared st and ard visits ( 20 minute follow-up and 40 minute new patient ) to a scribe system ( 15 minute follow-up and 30 minute new patient ) in a cardiology clinic . Physician productivity , patient satisfaction , physician – patient interaction , and revenue were measured . Results Four physicians saw 129 patients using st and ard care and 210 patients with scribes during 65 clinic hours each . Patients seen per hour increased ( P < 0.001 ) from 2.2 ± 0.3 to 3.5 ± 0.4 ( 59 % increase ) and work relative value units ( wRVU ) per hour increased ( P < 0.001 ) from 3.5 ± 1.3 to 5.5 ± 1.3 ( 57 % increase ) . Patient satisfaction was high at baseline and unchanged with scribes . In a sub study , direct patient contact time was lower ( 9.1 ± 2.0 versus 12.9 ± 3.4 minutes ; P < 0.01 ) for scribe visits , but time of patient interaction ( without computer ) was greater ( 6.7 ± 2.1 versus 1.5 ± 1.9 minutes ; P < 0.01 ) . Subjective assessment of physician – patient interaction ( 1–10 ) was higher ( P < 0.01 ) on scribe visits ( 9.1 ± 0.9 versus 7.9 ± 1.1 ) . Direct and indirect ( downstream ) revenue per patient seen was $ 142 and $ 2,398 , with $ 205,740 additional revenue generated from the 81 additional patients seen with scribes . Conclusion Using scribes in a cardiology clinic is feasible , produces improvements in physician – patient interaction , and results in large increases in physician productivity and system cardiovascular revenue BACKGROUND Scribes are unlicensed professionals trained in medical data entry . Limited data exist on the impact of scribes on provider time management in the emergency department ( ED ) . Time-motion analysis is a tool utilized in business to capture detailed movements and duration s to task completion . It offers a means to categorize how providers allocate their time during a clinical shift . OBJECTIVE Evaluate the impact of scribes on how ED providers spend their time . METHODS A prospect i ve observational study was conducted to assess scribe impact on provider time utilization . Four research assistants ( RAs ) observed attending providers on 24 8-h control shifts ( without a scribe ) , and 24 scribed shifts . RAs observed and categorized provider activity . Providers self-reported after-hours documentation times . Two- sample t-tests were used for normally distributed data , and Wilcoxon rank-sum tests were used for skewed data . All tests were two-sided , and p-values < 0.05 were considered statistically significant . RESULTS Scribes decreased total documentation time both on shift ( mean 55.3 vs. 36.4 min , p < 0.001 ) and post shift ( mean 42.5 vs. 23.3 min , p = 0.038 ) . They did not significantly decrease the amount of time spent review ing the medical records or placing orders , nor did they have an impact on provider time spent at patients ' bedside or time spent discussing patient care with team members . CONCLUSION The presence of scribes decreased provider documentation time but did not change the amount of time spent at the bedside or communicating with other team members . Scribes may be a potential strategy to decrease the clerical burden BACKGROUND Medical scribes are frequently incorporated into the patient care model to improve provider efficiency and enable providers to refocus their attention to the patient rather than the electronic health record ( EHR ) . The medical scribe program was based on four pillars ( objectives ): ( 1 ) provider satisfaction , ( 2 ) st and ardized documentation , ( 3 ) documentation components for risk adjustment , and ( 4 ) revenue enhancement . METHODS The medical scribe program was deployed in nine non-resident-supported clinics ( internal medicine , ophthalmology , orthopedics , hematology/oncology , urology ) , with the medical scribes ( who have no clinical duties ) supporting both physicians and advanced practice providers ( nurse practitioners and physician assistants ) . This paper describes a prospect i ve quasi-experimental study conducted at an academic , inner-city , hospital-based clinic system , RESULTS : A pre-post analysis showed positive results ; of the 51 providers , 44 responded to the survey pre and 41 responded post . Respondents in the post-scribe group felt that a scribe was valuable ( 90.2 % ) , that documentation time at the office improved ( 75.0 % poor or marginal pre-scribe , vs. 24 % post ; p < 0.0001 ) , and that time spent on the EHR at home declined ( 63.6 % with excessive or moderately high home EHR time pre vs. 31.7 % post ; p = 0.003 ) . More providers felt satisfied with their role in clinic with the use of scribes , and more providers felt that with scribes they could listen sufficiently to patients ( p < 0.05 ) . CONCLUSION Scribe support was well received across the institution in multiple clinical setting s. Benefits for providers were seen in documentation time and ability to listen to patients . Scribes appear to be an effective intervention for improving clinician work life Background : Medical scribes are a clinical innovation increasingly being used in primary care . The impact of scribes in primary care remain unclear . We aim ed to examine the impact of medical scribes on productivity , time spent facing the patient during the visit , and patient comfort with scribes in primary care . Methods : We conducted a prospect i ve observational pre-post study of 5 family and internal medicine-pediatrics physicians and their patients at an urban safety net health clinic . Medical scribes accompanied providers in the examination room and documented the clinical encounter . After an initial phase-in period , we added an additional 20-minute patient slot per 200-minute session . We examined productivity by using electronic medical record data on the number of patients seen and work relative value units ( work RVUs ) per hour . We directly observed clinical encounters to measure the amount of time providers spent facing patients and other visit components . We queried patient comfort with scribes by using surveys administered after the visit . Results : Work RVUs per hour increased by 10.5 % from 2.59 prescribe to 2.86 post-scribe ( P < .001 ) . Patients seen per hour increased by 8.8 % from 1.82 to 1.98 ( P < .001 ) . Work RVUs per patient did not change . After scribe implementation , time spent facing the patient increased by 57 % ( P < .001 ) and time spent facing the computer decreased by 27 % ( P = .003 ) . The proportion of the visit time that was spent face-to-face increased by 39 % ( P < .001 ) . Most ( 69 % ) patients reported feeling very comfortable with the scribe in the room , while the proportion feeling very comfortable with the number of people in the room decreased from 93 % to 66 % ( P < .001 ) . Conclusions : Although the full implication s of medical scribe implementation remain to be seen , this initial study highlights the promising opportunity of medical scribe implementation in primary care Abstract Objectives To evaluate the changes in productivity when scribes were used by emergency physicians in emergency departments in Australia and assess the effect of scribes on throughput . Design R and omised , multicentre clinical trial . Setting Five emergency departments in Victoria used Australian trained scribes during their respective trial periods . Sites were broadly representative of Australian emergency departments : public ( urban , tertiary , regional referral , paediatric ) and private , not for profit . Participants 88 physicians who were permanent , salaried employees working more than one shift a week and were either emergency consultants or senior registrars in their final year of training ; 12 scribes trained at one site and rotated to each study site . Interventions Physicians worked their routine shifts and were r and omly allocated a scribe for the duration of their shift . Each site required a minimum of 100 scribed and non-scribed shifts , from November 2015 to January 2018 . Main outcome measures Physicians ’ productivity ( total patients , primary patients ) ; patient throughput ( door-to-doctor time , length of stay ) ; physicians ’ productivity in emergency department regions . Self reported harms of scribes were analysed , and a cost-benefit analysis was done . Results Data were collected from 589 scribed shifts ( 5098 patients ) and 3296 non-scribed shifts ( 23 838 patients ) . Scribes increased physicians ’ productivity from 1.13 ( 95 % confidence interval 1.11 to 1.17 ) to 1.31 ( 1.25 to 1.38 ) patients per hour per doctor , representing a 15.9 % gain . Primary consultations increased from 0.83 ( 0.81 to 0.85 ) to 1.04 ( 0.98 to 1.11 ) patients per hour per doctor , representing a 25.6 % gain . No change was seen in door-to-doctor time . Median length of stay reduced from 192 ( interquartile range 108 - 311 ) minutes to 173 ( 96 - 208 ) minutes , representing a 19 minute reduction ( P<0.001 ) . The greatest gains were achieved by placing scribes with senior doctors at triage , the least by using them in sub-acute/fast track regions . No significant harm involving scribes was reported . The cost-benefit analysis based on productivity and throughput gains showed a favourable financial position with use of scribes . Conclusions Scribes improved emergency physicians ’ productivity , particularly during primary consultations , and decreased patients ’ length of stay . Further work should evaluate the role of the scribe in countries with health systems similar to Australia ’s . Trial registration ACTRN12615000607572 ( pilot site ) ; ACTRN12616000618459 Objectives : Assess the impact of scribes on an academic emergency department 's ( ED ) throughput one year after implementation . Methods : A prospect i ve cohort design compared throughput metrics of patients managed when scribes were and were not a part of the treatment team during pre‐defined study hours in a tertiary academic ED with both an adult and pediatric ED . An alternating‐day pattern one year following scribe implementation ensured balance between the scribe and non‐scribe groups in time of day , day of week , and patient complexity . Results : Adult : Overall length of stay ( LOS ) was essentially the same in both groups ( 214 vs. 215 min , p = 0.34 ) . In area A where staffing includes an attending and residents , scribes made a significant impact in treatment room time in the afternoon ( 190 vs 179 min , p = 0.021 ) with an increase in patients seen per hour on scribed days ( 2.00 vs. 2.13 ) . There was no statistically significant changes in throughput metrics in area B staffed by an attending and a nurse practitioner/physician assistant , however scribed days did average more patients per hour ( 2.01 vs. 2.14 ) . Pediatric : All throughput measurements were significantly longer when the treatment team had a scribe ; however , patients per hour increased from 2.33 to 2.49 on scribed days . Conclusions : Overall patient throughput was not enhanced by scribes . Certain areas and staffing combinations yielded improvements in treatment room and door to provider time , however , scribes appear to have enabled attending physicians to see more patients per hour . This effect varied across treatment areas and times of day |
540 | 32,197,619 | The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate . | Drug safety assessment s in clinical trials present unique analytical challenges .
Some of these include adjusting for individual follow-up time , repeated measurements of multiple outcomes and missing data among others .
Furthermore , pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected .
Although existing guidelines such as CONSORT encourage thorough reporting of adverse events ( AEs ) in clinical trials , they provide limited details for safety data analysis .
A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy .
Lack of proper st and ardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety .
Therefore , a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy . | Background Adjustment for prognostic covariates can lead to increased power in the analysis of r and omized trials . However , adjusted analyses are not often performed in practice . Methods We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas . We assessed ( 1 ) how large an increase in power can be expected in practice ; and ( 2 ) the impact of adjustment for covariates that are not prognostic . Results Adjustment for known prognostic covariates led to large increases in power for most outcomes . When power was set to 80 % based on an unadjusted analysis , covariate adjustment led to a median increase in power to 92.6 % across the 12 outcomes ( range 80.6 to 99.4 % ) . Power was increased to over 85 % for 8 of 12 outcomes , and to over 95 % for 5 of 12 outcomes . Conversely , the largest decrease in power from adjustment for covariates that were not prognostic was from 80 % to 78.5 % . Conclusions Adjustment for known prognostic covariates can lead to substantial increases in power , and should be routinely incorporated into the analysis of r and omized trials . The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so , and so should also be considered Background Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa . Low birthweight ( LBW , < 2,500 g ) is common in Papua New Guinea ( PNG ) and contributing factors include malaria and reproductive tract infections . Methods From November 2009 to February 2013 , we conducted a parallel group , r and omised controlled trial in pregnant women ( ≤26 gestational weeks ) in PNG . Sulphadoxine-pyrimethamine ( 1,500/75 mg ) plus azithromycin ( 1 g twice daily for 2 days ) ( SPAZ ) monthly from second trimester ( intervention ) was compared against sulphadoxine-pyrimethamine and chloroquine ( 450 to 600 mg , daily for three days ) ( SPCQ ) given once , followed by SPCQ placebo ( control ) . Women were assigned to treatment ( 1:1 ) using a r and omisation sequence with block sizes of 32 . Participants were blinded to assignments . The primary outcome was LBW . Analysis was by intention-to-treat . Results Of 2,793 women r and omised , 2,021 ( 72.4 % ) were included in the primary outcome analysis ( SPCQ : 1,008 ; SPAZ : 1,013 ) . The prevalence of LBW was 15.1 % ( 305/2,021 ) . SPAZ reduced LBW ( risk ratio [ RR ] : 0.74 , 95 % CI : 0.60–0.91 , P = 0.005 ; absolute risk reduction ( ARR ) : 4.5 % , 95 % CI : 1.4–7.6 ; number needed to treat : 22 ) , and preterm delivery ( 0.62 , 95 % CI : 0.43–0.89 , P = 0.010 ) , and increased mean birthweight ( 41.9 g , 95 % CI : 0.2–83.6 , P = 0.049 ) . SPAZ reduced maternal parasitaemia ( RR : 0.57 , 95 % CI : 0.35–0.95 , P = 0.029 ) and active placental malaria ( 0.68 , 95 % CI : 0.47–0.98 , P = 0.037 ) , and reduced carriage of gonorrhoea ( 0.66 , 95 % CI : 0.44–0.99 , P = 0.041 ) at second visit . There were no treatment-related serious adverse events ( SAEs ) , and the number of SAEs ( intervention 13.1 % [ 181/1,378 ] , control 12.7 % [ 174/1,374 ] , P = 0.712 ) and AEs ( intervention 10.5 % [ 144/1,378 ] , control 10.8 % [ 149/1,374 ] , P = 0.737 ) was similar . A major limitation of the study was the high loss to follow-up for birthweight . Conclusions SPAZ was efficacious and safe in reducing LBW , possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections . The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study . The ability of SPAZ to improve pregnancy outcomes warrants further evaluation . Trial registration Clinical Trials.gov NCT01136850 ( 06 April 2010 ) Background Intermittent preventive treatment with sulphadoxine-pyrimethamine ( IPTp-SP ) is being implemented in most malaria endemic countries as a st and ard two-doses regimen as it reduces the risk of low birth weight ( LBW ) and the prevalence of maternal anaemia . Nevertheless , where the risk of infection close to delivery is high because of intense transmission , a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome . Methods Pregnant women in the 2nd or 3rd trimester were r and omized to receive either 2 ( SP2 ) or 3 doses ( SP3 ) of SP . Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule . Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed . The prevalence of LBW ( < 2500 g ) , severe anaemia ( Hb < 8 g/dL ) and premature birth was analysed using intention-to-treat ( ITT ) and per- protocol ( PP ) analysis . Results Data from 1274 singleton pregnancies were analysed ( 641 in the SP3 and 633 in the SP2 group ) . The uptake of the intervention appeared to be low . Though the prevalence of LBW in both intervention groups was similar ( adjusted Incident Rate Ratio , AIRR = 0.92 , 95%CI : 0.69 - 1.24 ) in the ITT analysis , the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group ( AIRR = 0.38 , 95%CI : 0.16 - 0.90 ) . The PP analysis showed a trend of reduced risk of LBW , severe anaemia and premature delivery in the SP3 group , albeit the difference between two and three IPTp-SP did not reach statistical significance . Conclusion The risk of LBW and severe anaemia tended to be lower in the SP3 group , though this was not statistically significant , probably due to the low uptake of the intervention which reduced the power of the study . Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in setting s where transmission is markedly seasonal Background Daily trimethoprim-sulfamethoxazole ( TMP-SMX ) and insecticide-treated nets remain the main interventions for prevention of malaria in human immunodeficiency virus (HIV)-infected pregnant women in Africa . However , antifolate and pyrethroid resistance threaten the effectiveness of these interventions , and new ones are needed . Methods We conducted a double-blinded , r and omized , placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine ( DP ) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Ug and a where indoor residual spraying of insecticide had recently been implemented . Participants were enrolled between gestation weeks 12 and 28 and given an insecticide-treated net . The primary outcome was detection of active or past placental malarial infection by histopathologic analysis . Secondary outcomes included incidence of malaria , parasite prevalence , and adverse birth outcomes . Result All 200 women enrolled were followed through delivery , and the primary outcome was assessed in 194 . There was no statistically significant difference in the risk of histopathologically detected placental malarial infection between the daily TMP-SMX plus DP arm and the daily TMP-SMX alone arm ( 6.1 % vs. 3.1 % ; relative risk , 1.96 ; 95 % confidence interval , .50 - 7.61 ; P = .50 ) . Similarly , there were no differences in secondary outcomes . Conclusions Among HIV-infected pregnant women in the setting of indoor residual spraying of insecticide , adding monthly DP to daily TMP-SMX did not reduce the risk of placental or maternal malaria or improve birth outcomes . Clinical Trials Registration NCT02282293 BACKGROUND In 2003 , Mali introduced intermittent preventive therapy in pregnancy ( ITPp ) with sulfadoxine-pyrimethamine ( SP ) for the control of malaria in pregnancy , consisting of 2 doses of SP given in the 2nd and 3rd trimester . This widely used regimen , although very effective , leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation , which is a pivotal period for fetal weight gain . The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight ( LBW ) . METHODS We conducted a parallel-group , open-label , individually r and omized controlled superiority trial involving 814 women of all gravidity , enrolled from April 2006 through March 2008 . All women were seen at least 3 times and received either 2 ( n = 401 ) or 3 ( n = 413 ) doses of IPTp-SP . The primary endpoint measured was placental malaria , LBW , preterm births , and maternal anemia were secondary endpoints , and severe maternal skin reactions and neonatal jaundice were safety endpoints . RESULTS Among the 96 % of study subjects who were followed up until delivery , the prevalence of placental malaria was 2-fold lower in the 3-dose group ( 8.0 % ) than in the 2-dose group ( 16.7 % ) ; the adjusted prevalence ratio ( APR ) was 0.48 ( 95 % confidence interval [ CI ] , 0.32 - 0.71 ) . LBW and preterm births were also reduced ; the prevalence of LBW was 6.6 % in the 3-dose group versus 13.3 % in the 2-dose group ( APR , 0.50 ; 95 % CI , 0.32 - 0.79 ) , and the prevalence of preterm births was 3.2 % versus 8.9 % ( APR , 0.37 ; 95 % CI , 0.19 - 0.71 ) . No significant reductions in maternal anemia or differences in safety endpoints were observed . CONCLUSIONS Adding a third dose of ITPp-SP halved the risk of placental malaria , LBW , and preterm births in all gravidae , compared with the st and ard 2-dose regimen , in this area of highly seasonal transmission with low levels of SP resistance . CLINICAL TRIALS REGISTRATION IS RCT N 74189211 BACKGROUND Intermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa . However , with the spread of resistance to sulfadoxine-pyrimethamine , new interventions are needed . METHODS We conducted a double-blind , r and omized , controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Ug and a , where sulfadoxine-pyrimethamine resistance is widespread . We r and omly assigned participants to a sulfadoxine-pyrimethamine regimen ( 106 participants ) , a three-dose dihydroartemisinin-piperaquine regimen ( 94 participants ) , or a monthly dihydroartemisinin-piperaquine regimen ( 100 participants ) . The primary outcome was the prevalence of histopathologically confirmed placental malaria . RESULTS The prevalence of histopathologically confirmed placental malaria was significantly higher in the sulfadoxine-pyrimethamine group ( 50.0 % ) than in the three-dose dihydroartemisinin-piperaquine group ( 34.1 % , P=0.03 ) or the monthly dihydroartemisinin-piperaquine group ( 27.1 % , P=0.001 ) . The prevalence of a composite adverse birth outcome was lower in the monthly dihydroartemisinin-piperaquine group ( 9.2 % ) than in the sulfadoxine-pyrimethamine group ( 18.6 % , P=0.05 ) or the three-dose dihydroartemisinin-piperaquine group ( 21.3 % , P=0.02 ) . During pregnancy , the incidence of symptomatic malaria was significantly higher in the sulfadoxine-pyrimethamine group ( 41 episodes over 43.0 person-years at risk ) than in the three-dose dihydroartemisinin-piperaquine group ( 12 episodes over 38.2 person-years at risk , P=0.001 ) or the monthly dihydroartemisinin-piperaquine group ( 0 episodes over 42.3 person-years at risk , P<0.001 ) , as was the prevalence of parasitemia ( 40.5 % in the sulfadoxine-pyrimethamine group vs. 16.6 % in the three-dose dihydroartemisinin-piperaquine group [ P<0.001 ] and 5.2 % in the monthly dihydroartemisinin-piperaquine group [ P<0.001 ] ) . In each treatment group , the risk of vomiting after administration of any dose of the study agents was less than 0.4 % , and there were no significant differences among the groups in the risk of adverse events . CONCLUSIONS The burden of malaria in pregnancy was significantly lower among adolescent girls or women who received intermittent preventive treatment with dihydroartemisinin-piperaquine than among those who received sulfadoxine-pyrimethamine , and monthly treatment with dihydroartemisinin-piperaquine was superior to three-dose dihydroartemisinin-piperaquine with regard to several outcomes . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ; Clinical Trials.gov number , NCT02163447 . ) BACKGROUND Human immunodeficiency virus ( HIV ) and malaria during pregnancy cause substantial perinatal mortality . As co-trimoxazole ( CMX ) protects children and HIV-positive adults against malaria , we compared the effectiveness of daily CMX with sulfadoxine-pyrimethamine intermittent preventive treatment ( IPT-SP ) on malaria risk in HIV-positive pregnant women in a Plasmodium falciparum-endemic African area . METHODS From January 2009 to April 2011 , we included in a r and omized noninferiority trial all HIV type 1-infected pregnant women ( ≤28 weeks ' gestation , CD4 count ≥200 cells/µL , hemoglobin level ≥7 g/L ) in 19 health centers in Togo . Women were r and omly assigned to daily 800 mg/160 mg CMX , or IPT-SP . The primary outcome was the proportion of malaria-free pregnancies . Other outcomes included malaria incidence , parasitemia , placental malaria , anemia , and infants ' birth weight . RESULTS Of 264 women r and omly assigned to the CMX or IPT-SP group , 126 of 132 and 124 of 132 , respectively , were included in the analysis . There were 33 confirmed cases of clinical malaria among 31 women in the CMX group , and 19 among 19 women in the IPT-SP group . Ninety-five of 126 ( 75.4 % ) women in the CMX group and 105 of 124 ( 84.7 % ) in the IPT-SP group remained malaria-free during their pregnancy ( difference , 9.3 % ; 95 % confidence interval [ CI ] , -.53 to 19.1 , not meeting the predefined noninferiority criterion ) . The incidence rate in intention-to-treat analysis was 108.8 malaria episodes per 100 person-years in CMX ( 95 % CI , 105.4 - 112.2 ) and 90.1 in IPT-SP ( 95 % CI , 86.8 - 93.4 ) ( not significant ) . Prevalence of parasitemia was 16.7 % in the CMX group vs 28 % in the IPT-SP group ( P = .02 ) . Histology revealed 20.3 % placental malaria in the CMX group vs. 24.6 % in the IPT-SP group ( not significant ) . Grade 3 - 4 anemia was more frequent in the CMX group ( 10 % vs 4 % ; P = .008 ) . No pregnant women died . Median birth weight was similar . CONCLUSIONS Daily CMX was not noninferior to IPT-SP for preventing maternal malaria but safe and at least similar regarding parasitemia or placental malaria and birth outcomes . Clinical Trials Registration IS RCT N98835811 Clara Menéndez and colleagues conducted a r and omized controlled trial among HIV-positive pregnant women in Kenya , Mozambique , and Tanzania to investigate the safety and efficacy of mefloquine as intermittent preventative therapy for malaria in women receiving cotrimoxazole prophylaxis and long-lasting insecticide treated nets . Please see later in the article for the Editors ' Objective R and omised controlled trials ( RCTs ) are often considered as the gold st and ard for assessing new health interventions . Patients are r and omly assigned to receive an intervention or control . The effect of the intervention can be estimated by comparing outcomes between groups , whose prognostic factors are expected to balance by r and omisation . However , patients ’ non-compliance with their assigned treatment will undermine r and omisation and potentially bias the estimate of treatment effect . Through simulation , we aim to compare common approaches in analysing non-compliant data under different non-compliant scenarios . Setting s Based on a real study , we simulated hypothetical trials by varying three non-compliant factors : the type , r and omness and degree of non-compliance . We compared the intention-to-treat ( ITT ) , as-treated ( AT ) , per- protocol ( PP ) , instrumental variable ( IV ) and complier average casual effect ( CACE ) analyses to estimate large ( 50 % improvement over the control ) , moderate ( 25 % improvement ) and null ( same as the control ) treatment effects . Different approaches were compared by the bias of estimate , mean square error ( MSE ) and 95 % coverage of the true value . Results For a large or moderate treatment effect , the ITT estimate was considerably biased in all scenarios . The AT , PP , IV and CACE estimates were unbiased when non-compliant behaviours were r and om . The IV estimate was unbiased when non-compliant behaviours were symmetrically dependent on patients ’ conditions . The PP estimate was mostly unbiased when patients in the control group did not have access to the intervention . When the intervention was not different from the control , the ITT was less biased than the other approaches . Similar results were found when comparing the MSE and 95 % coverage . Conclusions The st and ard ITT analysis under non-compliance is biased when the intervention has a moderate or large effect . Alternative analyses can provide unbiased or less biased estimates . Based on the results , we make some suggestions on choosing optimal approaches for analysing specific non-compliant scenarios When the aim of the r and omized controlled trial ( RCT ) is to show that one treatment is superior to another , a statistical test is employed and the trial ( test ) is called a superiority trial ( test ) . Often a nonsignificant superiority test is wrongly interpreted as proof of no difference between the two treatments . Proving that two treatments are equal in performance is impossible with statistical tools ; at most , one can show that they are equivalent . In an equivalence trial , the statistical test aims at showing that two treatments are not too different in characteristics , where " not too different " is defined in a clinical manner . Finally , in a non-inferiority trial , the aim is to show that an experimental treatment is not ( much ) worse than a st and ard treatment . In this report , the three types of trials are compared , but the main focus is on the non-inferiority trial . Special attention is paid to the practical implication s when setting up a non-inferiority trial . Illustrations are taken from a clinical trial in osteoarthritis and from thrombolytic research Introduction Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes . No studies have been done so far on the effects of daily Co-trimoxazole ( CTX ) prophylaxis on birth outcomes . A phase 3b r and omized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment ( IPT ) in reducing placental malaria ; preventing peripheral parasitaemia ; preventing perinatal mortality and also improving birth weight . To establish its safety on the offspring by measuring the gestational age and birth weight at delivery , and compare the safety and efficacy profile of CTX to that of SP . Methods Pregnant women ( HIV infected and uninfected ) attending antenatal clinic were r and omized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT . Safety was assessed using st and ard and pregnancy specific measurements . Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery . Results Data from 346 pregnant women ( CTX = 190 ; SP = 156 ) and 311 newborns ( CTX = 166 and SP = 145 ) showed that preterm deliveries ( CTX 3.6 % ; SP 3.0 % ) ; still births ( CTX 3.0 % ; SP 2.1 % ) , neonatal deaths ( CTX 0 % ; SP 1.4 % ) , and spontaneous abortions ( CTX 0.6 % ; SP 0 % ) were similar between study arms . The low birth weight rates were 9 % for CTX and 13 % for SP . There were no birth defects reported . Both drug exposure groups had full term deliveries with similar birth weights ( mean of 3.1 Kg ) . The incidence and severity of AEs in the two groups were comparable . Conclusion Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries , still births , neonatal deaths and spontaneous abortions compared to SP . However , more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals . Trial Registration Clinical trials.gov NCT00711906 OBJECTIVE To compare the effectiveness of mefloquine and sulphadoxine-pyrimethamine as intermittent preventive therapy for malaria among pregnant women with HIV . METHODS The present r and omized , controlled , prospect i ve , open-label study enrolled women with HIV who had reached at least 16 weeks of pregnancy attending prenatal clinics at secondary and tertiary health facilities in South West Nigeria between January 1 and August 31 , 2016 . Block r and omization was used to assign patients to treatment with mefloquine or sulphadoxine-pyrimethamine for malaria prophylaxis . The primary outcome was malaria parasitemia at delivery . Data were compared with the χ2 and t tests on a per- protocol basis . RESULTS Of 142 women enrolled and r and omized equally to each group , 131 ( 92.3 % ) completed the study ( 64 in the mefloquine group and 67 in the sulphadoxine-pyrimethamine group ) . Blood- sample malaria parasites were isolated from 6 ( 9 % ) and 5 ( 7 % ) patients in the mefloquine and sulphadoxine-pyrimethamine groups , respectively , at enrolment , and 6 ( 9 % ) and 9 ( 13 % ) patients in the mefloquine and sulphadoxine-pyrimethamine groups , respectively , at delivery ; the differences between the groups was not significant at enrolment ( P=0.693 ) or delivery ( P=0.466 ) . CONCLUSION Outcomes following prophylactic use of mefloquine for intermittent preventive therapy for malaria among pregnant women with HIV were comparable to sulphadoxine-pyrimethamine treatment ; mefloquine is a feasible alternative therapy . Clinical Trials.gov : NCT02524444 Background The World Health Organization recommends intermittent preventive treatment in pregnancy ( IPTp ) with sulfadoxine-pyrimethamine ( SP ) in African regions with moderate to high malaria transmission . However , growing resistance to SP threatens the effectiveness of IPTp-SP , and alternative drugs are needed . This study tested the efficacy , tolerability , and safety of a fixed-dose combination azithromycin-chloroquine ( AZCQ ; 250 mg AZ/155 mg CQ base ) for IPTp relative to IPTp-SP . Methods and Findings A r and omized , Phase 3 , open-label , multi-center study was conducted in sub-Saharan Africa ( Benin , Kenya , Malawi , Tanzania , and Ug and a ) between October 2010 and November 2013 . Pregnant women received 3 IPTp courses with AZCQ ( each course : 1,000/620 mg AZCQ QD for 3 days ) or SP ( each course 1,500/75 mg SP QD for 1 day ) at 4- to 8-week intervals during the second and third trimester . Long-lasting insecticide-treated bednets were also provided at enrollment . Study participants were followed up until day 28 post delivery ( time window : day 28–42 ) . The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes ( a composite endpoint comprising live-borne neonates with low birth weight [ LBW , < 2,500 g ] , premature birth [ < 37 weeks ] , still birth [ > 28 weeks ] , abortion [ ≤28 weeks ] , lost to follow-up prior to observation of pregnancy outcome , or missing birth weight ) . The study was terminated early after recruitment of 2,891 of the planned 5,044 participants , due to futility observed in a pre-specified 35 % interim analysis . In the final intent-to-treat data set , 378/1,445 ( 26.2 % ) participants in the AZCQ and 342/1,445 ( 23.7 % ) in the SP group had sub-optimal pregnancy outcomes , with an estimated risk ratio ( RR ) of 1.11 ( 95 % CI : 0.97 , 1.25 ; p = 0.12 ) . There was no significant difference in the incidence of LBW between treatment groups ( 57/1138 [ 5.0 % ] in the AZCQ group , 68/1188 [ 5.7 % ] in the SP group , RR 0.87 [ 95 % CI : 0.62 , 1.23 ] ; p = 0.44 ) . IPTp-AZCQ was less well-tolerated in mothers than IPTp-SP . Occurrences of congenital anomalies , deaths , and serious adverse events were comparable in neonates for both groups . Limitations included the open-label design and early study termination . Conclusions IPTp-AZCQ was not superior to IPTp-SP in this study and alternatives for IPTp-SP remain to be identified . The proportions of sub-optimal pregnancy outcomes and LBW were lower than expected , which may be linked to insecticide-treated bednet use throughout the study . Reduced incidences of symptomatic malaria infection and peripheral parasitemia in the AZCQ group relative to SP suggest that AZCQ warrants further investigation as an alternative treatment of uncomplicated malaria . Trial Registration Clinical Trials.gov ( NCT01103063 ) Background : Malaria during pregnancy has serious consequences that are worsened by HIV infection . Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole ( CTX ) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria , or intermittent preventive treatment ( IPTp ) with an antimalarial drug . Here , we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp , alone and in combination , in HIV-infected pregnant women . Methods : We conducted 2 r and omized , open-label , noninferiority trials in Benin . In the CTX-m and atory trial , HIV-infected women with CD4 counts of < 350 per cubic millimeter received CTX either alone or with MQ-IPTp ( N = 292 ) . In the CTX-not-m and atory trial ( CD4 count > 350/mm3 ) , CTX was compared with MQ-IPTp ( N = 140 ) . In both the trials , the primary end point was microscopic placental parasitemia . Results : At delivery , 1 woman in each CTX-alone treatment group exhibited placental parasitemia , versus no women in the groups receiving MQ . CTX alone demonstrated noninferiority in the CTX-m and atory trial . However , polymerase chain reaction – detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone ( 0/105 vs. 5/103 , P = 0.03 ) . Because of insufficient recruitment in the CTX-not-m and atory trial , noninferiority could not be conclusively assessed . Dizziness and vomiting of moderate intensity were reported by 34%–37 % of women receiving MQ in both the trials , versus 0%–3 % in CTX groups ( P < 0.0001 ) . No serious adverse events related to these drugs were found . Conclusions : CTX alone provided adequate protection against malaria in HIV-infected pregnant women , although MQ-IPTp showed higher efficacy against placental infection . Although more frequently associated with dizziness and vomiting , MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX Clara Menéndez and colleagues conducted an open-label r and omized controlled trial in HIV-negative pregnant women in Benin , Gabon , Mozambique , and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria . Please see later in the article for the Editors ' Intermittent preventive treatment of malaria during pregnancy ( IPTp ) and insecticide-treated nets ( ITN ) are recommended malaria interventions during pregnancy ; however , there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa . An individually-r and omised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp , ITNs alone , or ITNs used in combination with IPTp on maternal anaemia and low birth weight ( LBW ) in a highl and area of southwestern Ug and a. The overall prevalence of malaria infection , maternal anaemia and LBW was 15.0 % , 14.7 % and 6.5 % , respectively . Maternal and fetal outcomes were generally remarkably similar across all intervention groups ( P>0.05 for all outcomes examined ) . A marginal difference in maternal haemoglobin was observed in the dual intervention group ( 12.57g/dl ) compared with the IPTp and ITN alone groups ( 12.40g/dl and 12.44g/dl , respectively ; P=0.04 ) , but this was too slight to be of clinical importance . In conclusion , none of the preventive strategies was found to be superior to the others , and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed . With ITNs offering a number of advantages over IPTp , yet showing comparable efficacy , we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Preterm delivery , which is associated with infections during pregnancy , is common in sub-Saharan Africa . We enrolled 1,320 pregnant women into a r and omized , controlled trial in Malawi to study whether preterm delivery and low birth weight ( LBW ) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections . The participants received either sulfadoxine-pyrimethamine ( SP ) twice ( controls ) , monthly SP , or monthly SP and two doses of azithromycin ( AZI-SP ) . The incidence of preterm delivery was 17.9 % in controls , 15.4 % in the monthly SP group ( P = 0.32 ) , and 11.8 % in AZI-SP group ( risk ratio = 0.66 , P = 0.01 ) . Compared with controls , those in AZI-SP group had a risk ratio of 0.61 ( P = 0.02 ) for LBW . Incidence of serious adverse events was low in all groups . In conclusion , the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses True intention-to-treat analyses are rare in reports of r and omized clinical trials . To highlight the complex issues that arise in conducting and interpreting data from intention-to-treat analyses in studies with substantial levels of protocol violation ( e.g. attrition , noncompliance , or withdrawal of participants ) , data from a clinical trial of treatment for cocaine dependence were analyzed using three strategies to manage missing data : Strategy 1 addressed the effectiveness of treatments based on data collected from participants up to the point of dropout . Strategy 2 addressed the effectiveness of treatments based on data from the full intended duration of the protocol including data collected after participant dropout . The third strategy used a more novel approach , which used an intention-to-treat strategy for the full duration of the trial and the full sample , but also evaluated the effect of treatment retention outcomes by including an independent variable to reflect active treatment retention as a time-varying covariate . Conclusions about the relative efficacy of the study treatments varied to some extent depending on the analytic strategy used . These findings suggest that investigators should make every effort to conduct intent-to-treat analyses , but also to make use of multiple analytic strategies to fully underst and the effects of the treatments studied . Moreover , regardless of the strategy used , investigators should clearly describe their h and ling of data from participants who violate the protocol BACKGROUND Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy , and alternative regimens need to be identified . With the return of chloroquine efficacy in southern Africa , we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes . METHODS We did an open-label , single-centre , r and omised controlled trial at Ndir and e Health Centre , Blantyre , in southern Malawi . We enrolled pregnant women ( first or second pregnancy ) at 20 - 28 weeks ' gestation who were HIV negative . Participants were r and omly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine ( two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine , 4 weeks apart ) , intermittent chloroquine ( two doses of 600 mg on day 1 , 600 mg on day 2 , and 300 mg on day 3 ) , or chloroquine prophylaxis ( 600 mg on day 1 then 300 mg every week ) . The primary endpoint was placental malaria in the modified intent-to-treat population , which consisted of participants who contributed placental histopathology data at birth . Secondary outcomes included clinical malaria , maternal anaemia , low birthweight , and safety . This trial is registered with Clinical Trials.gov , number NCT01443130 . FINDINGS Between February , 2012 , and May , 2014 , we enrolled and r and omly allocated 900 women , of whom 765 contributed histopathological data and were included in the primary analysis . 108 ( 14 % ) women had placental malaria , which was lower than the anticipated prevalence of placental malaria infection . Protection from placental malaria was not improved by chloroquine as either prophylaxis ( 30 [ 12 % ] of 259 had positive histopathology ; relative risk [ RR ] 0·75 , 95 % CI 0·48 - 1·17 ) or intermittent therapy ( 39 [ 15 % ] of 253 ; RR 1·00 , 0·67 - 1·50 ) compared with intermittent sulfadoxine-pyrimethamine ( 39 [ 15 % ] of 253 ) . In protocol -specified analyses adjusted for maternal age , gestational age at enrolment , bednet use the night before enrolment , anaemia at enrolment , and malaria infection at enrolment , women taking chloroquine as prophylaxis had 34 % lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine ( RR 0·66 , 95 % CI 0·46 - 0·95 ) . Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine , four allocated intermittent chloroquine ( p=0·26 ) , and two allocated chloroquine prophylaxis ( p=0·063 ) . Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine , 15 allocated intermittent chloroquine ( p=0·038 ) , and six assigned chloroquine prophylaxis ( p>0·99 ) . Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine , 29 assigned intermittent chloroquine ( p=0·78 ) , and 41 allocated chloroquine prophylaxis ( p=0·28 ) . Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine ( p<0·0001 ) and 26 allocated chloroquine prophylaxis ( p<0·0001 ) . Three women had severe or life-threatening adverse events related to study product , of whom all were assigned intermittent chloroquine ( p=0·25 ) . INTERPRETATION Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine . Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy , but studies with larger sample sizes are needed to confirm these results . FUNDING US National Institutes of Health Objective To ascertain contemporary approaches to the collection , reporting and analysis of adverse events ( AEs ) in r and omised controlled trials ( RCTs ) with a primary efficacy outcome . Design A review of clinical trials of drug interventions from four high impact medical journals . Data sources Electronic contents table of the BMJ , the Journal of the American Medical Association ( JAMA ) , the Lancet and the New Engl and Journal of Medicine ( NEJM ) were search ed for reports of original RCTs published between September 2015 and September 2016 . Methods A prepiloted checklist was used and single data extraction was performed by three review ers with independent check of a r and omly sample d subset to verify quality . We extracted data on collection methods , assessment of severity and causality , reporting criteria , analysis methods and presentation of AE data . Results We identified 184 eligible reports ( BMJ n=3 ; JAMA n=38 , Lancet n=62 and NEJM n=81 ) . Sixty-two per cent reported some form of spontaneous AE collection but only 29 % included details of specific prompts used to ascertain AE data . Numbers that withdrew from the trial were well reported ( 80 % ) , however only 35 % of these reported whether withdrawals were due to AEs . Results presented and analysis performed was predominantly on ‘ patients with at least one event ’ with 84 % of studies ignoring repeated events . Despite a lack of power to undertake formal hypothesis testing , 47 % performed such tests for binary outcomes . Conclusions This review highlighted that the collection , reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underused . Areas to improve include reducing information loss when analysing at patient level and inappropriate practice of underpowered multiple hypothesis testing . Implementation of st and ard reporting practice s could enable a more accurate synthesis of safety data and development of guidance for statistical methodology to assess causality of AEs could facilitate better statistical practice BACKGROUND Intermittent treatment with sulfadoxine-pyrimethamine , recommended for prevention of malaria in pregnant women throughout sub-Saharan Africa , is threatened by parasite resistance . We assessed the efficacy and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine . METHODS We did a double-blind , r and omised , controlled , superiority trial at one rural site in Ug and a with high malaria transmission and sulfadoxine-pyrimethamine resistance . HIV-uninfected pregnant women between 12 and 20 weeks gestation were r and omly assigned ( 1:1 ) to monthly intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine . The primary endpoint was the risk of a composite adverse birth outcome defined as low birthweight , preterm birth , or small for gestational age in livebirths . Protective efficacy was defined as 1-prevalence ratio or 1-incidence rate ratio . All analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT02793622 . FINDINGS Between Sept 6 , 2016 , and May 29 , 2017 , 782 women were enrolled and r and omly assigned to receive sulfadoxine-pyrimethamine ( n=391 ) or dihydroartemisinin-piperaquine ( n=391 ) ; 666 ( 85·2 % ) women who delivered livebirths were included in the primary analysis . There was no significant difference in the risk of our composite adverse birth outcome between the dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine treatment group ( 54 [ 16 % ] of 337 women vs 60 [ 18 % ] of 329 women ; protective efficacy 12 % [ 95 % CI -23 to 37 ] , p=0·45 ) . Both drug regimens were well tolerated , with no significant differences in adverse events between the groups , with the exception of asymptomatic corrected QT interval prolongation , which was significantly higher in the dihydroartemisinin-piperaquine group ( mean change 13 ms [ SD 23 ] ) than in the sulfadoxine-pyrimethamine group ( mean change 0 ms [ SD 23 ] ; p<0·0001 ) . INTERPRETATION Monthly intermittent preventive treatment with dihydroartemisinin-piperaquine was safe but did not lead to significant improvements in birth outcomes compared with sulfadoxine-pyrimethamine . FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development , and Bill & Melinda Gates Foundation BACKGROUND Every year , more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences . The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance . We aim ed to assess the efficacy and safety of two alternative strategies : intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine , and intermittent preventive treatment with dihydroartemisinin-piperaquine . METHODS We did this open-label , three-group , r and omised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance . HIV-negative pregnant women between 16 and 32 weeks ' gestation were r and omly assigned ( 1:1:1 ) , via computer-generated permuted-block r and omisation ( block sizes of three , six , and nine ) , to receive intermittent screening and treatment with dihydroartemisinin-piperaquine , intermittent preventive treatment with dihydroartemisinin-piperaquine , or intermittent preventive treatment with sulfadoxine-pyrimethamine . Study participants , study clinic nurses , and the study coordinator were aware of treatment allocation , but allocation was concealed from study investigators , delivery unit nurses , and laboratory staff . The primary outcome was malaria infection at delivery , defined as a composite of peripheral or placental parasitaemia detected by placental histology , microscopy , or rapid diagnostic test . The primary analysis was by modified intention to treat . This study is registered with Clinical Trials.gov , number NCT01669941 . FINDINGS Between Aug 21 , 2012 , and June 19 , 2014 , we r and omly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine ( n=515 ) , intermittent preventive treatment with dihydroartemisinin-piperaquine ( n=516 ) , or intermittent preventive treatment with sulfadoxine-pyrimethamine ( n=515 ) ; 1368 ( 88 % ) women comprised the intention-to-treat population for the primary endpoint . Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group ( 15 [ 3 % ] of 457 women vs 47 [ 10 % ] of 459 women ; relative risk 0·32 , 95 % CI 0·18 - 0·56 ; p<0·0001 ) , but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group ( 57 [ 13 % ] of 452 women ; 1·23 , 0·86 - 1·77 ; p=0·26 ) . Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine , intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy ( 192·0 vs 54·4 events per 100 person-years ; incidence rate ratio [ IRR ] 0·28 , 95 % CI 0·22 - 0·36 ; p<0·0001 ) and clinical malaria during pregnancy ( 37·9 vs 6·1 events ; 0·16 , 0·08 - 0·33 ; p<0·0001 ) , whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection ( 232·0 events ; 1·21 , 1·03 - 1·41 ; p=0·0177 ) and clinical malaria ( 53·4 events ; 1·41 , 1·00 - 1·98 ; p=0·0475 ) . We recorded 303 maternal and infant serious adverse events , which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group . INTERPRETATION At current levels of rapid diagnostic test sensitivity , intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission . However , dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment . Future studies should investigate the efficacy , safety , operational feasibility , and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine . FUNDING The Malaria in Pregnancy Consortium , which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine |
541 | 32,294,971 | At the multivariate meta-regression , the effect of publication year was significant , as well as the effects of country , gender , and level .
Conclusions : RT has a significant impact in h and ball players . | Purpose : H and ball ( Team H and ball ) is an intermittent and strenuous contact sport , the successful performance of which depends on frequent body contacts , and the ability to make repeated explosive muscular contractions required for jumping , acceleration , sprinting , turning , changing pace , and throwing a ball .
Many studies have investigated the effect of resistance training ( RT ) in h and ball players , however with conflicting results .
Therefore , our objective was to investigate the impact of RT on maximal strength ( isometric and isokinetic strength ) , the power of both lower and upper limbs , and throwing velocity , in h and ball players . | Hermassi , S , Chelly , MS , Fathloun , M , and Shephard , RJ . The effect of heavy- vs. moderate-load training on the development of strength , power , and throwing ball velocity in male h and ball players . J Strength Cond Res 24(X ) : 000 - 000 , 2010-The aim was to compare the effect of 2 differing 10-week resistance training programs on the peak power ( PP ) output , muscle volume , strength , and throwing velocity of the upper limbs in h and ball players during the competitive season . The subjects were 26 men ( age 20.0 ± 0.6 years , body mass 85.0 ± 13.2 kg , height 1.86 ± 0.06 m , and body fat 13.7 ± 2.4 % ) . They were r and omly assigned to 1 of 3 groups : control ( C ; n = 8) , heavy resistance ( n = 9 ) , or moderate resistance ( MR ; n = 9 ) training , performed twice a week . A force-velocity test on an appropriately modified Monark cycle ergometer determined PP . Muscle volumes were estimated using a st and ard anthropometric kit . One-repetition maximum ( 1RM ) bench press ( 1RMBP ) and 1RM pull-over ( 1RMPO ) scores assessed arm strength . H and ball throwing velocity was measured with ( TR ) and without run-up ( TW ) . Both training programs enhanced absolute PP relative to controls ( p < 0.05 ) , although differences disappeared if PP was expressed per unit of muscle volume . Heavy resistance-enhanced 1RMBP and 1RMPO compared to both MR ( p < 0.01 and p < 0.05 , respectively ) and C ( p < 0.001 for both tests ) . Heavy resistance also increased TR and TW compared to C ( p < 0.01 and p < 0.05 , respectively ) . Moderate resistance increased only TR compared to C ( p < 0.01 ) . Thus , during the competitive season , the PP , 1RMBP , 1RMPO , and TW of male h and ball players were increased more by 10 weeks of bench press and pull-over training with suitably adapted heavy loads than with moderate loads . It would seem advantageous to add such resistance exercise before customary technical and tactical h and ball training sessions Abstract Raeder , C , Fern and ez-Fern and ez , J , and Ferrauti , A. Effects of six weeks of medicine ball training on throwing velocity , throwing precision , and isokinetic strength of shoulder rotators in female h and ball players . J Strength Cond Res 29(7 ) : 1904–1914 , 2015—The aim of this study was to investigate the effects of 6 weeks of medicine ball training ( MBT ) on throwing velocity , throwing precision , and isokinetic strength of shoulder rotators in competitive female h and ball players . Twenty-eight players ( mean ± SD ; age : 20.8 ± 3.3 years , height : 170.5 ± 5.6 cm , body mass : 65.2 ± 8.0 kg ) were r and omly assigned to an MBT group ( TG ; n = 15 ) and a control group ( CG ; n = 13 ) . TG performed a supervised MBT program , 3 times a week for a total of 6 weeks , focusing on h and ball-specific movement patterns . Both groups , TG and CG , also conducted a supervised shoulder injury prevention program with elastic tubes , as part of the warm-up , finishing with regular h and ball throws . Results showed a significant group × time interaction in throwing velocity ( p < 0.001 ) with the TG posttest results being significantly higher compared with CG ( d = 2.1 ) , and also a significant main time effect ( p < 0.001 ) , with an increase in throwing velocity of 14 % ( d = 3.0 ) and 3.7 % ( d = 0.3 ) for both TG and CG , respectively . Throwing precision did not significantly differ between groups and time points . Isokinetic strength measures revealed a significant group × time interaction ( p ⩽ 0.05 ) with the TG posttest results being significantly higher compared with CG ( d = 0.9 ) and also a significant main time effect ( p < 0.01 ) with an increase of 15 % ( d = 0.9 ) in concentric shoulder internal rotation at 180 ° ·s−1 in the dominant arm in TG , whereas no significant changes occurred in CG . The present results indicate that 6 weeks of MBT elicit significant improvements in functional performance ( i.e. , throwing velocity ) in female h and ball players , whereas throwing precision remained unaffected . Medicine ball training exercises seem to be a useful and inexpensive strength training strategy in enhancing functional performance by closely mimicking sport-specific movement activities PURPOSE The purpose of this study was to compare the effects of jump training as a complement to weight training on jump performance and muscle strategy during the squat and countermovement jump . METHOD Twenty-two male h and ball players , between the ages of 17 and 24 , and in good health , were r and omly divided into three groups . Two were trained groups , weight training ( WTG ) and jump training combined with weight training ( CTG ) , and one was a control group ( CG ) . Maximal isometric force and maximal concentric power were assessed by a supine leg press , squat jump ( SJ ) , counter movement jump ( CMJ ) , and surface EMG was used to determine changes in muscle adaptation before and after the training period . RESULTS After 6-wk training programs , the two training groups increased maximal isometric force , maximal concentric power , and squat jump performance . However , only combined training presented a significant increase in height jump performance during the countermovement jump ( P < 0.05 ) . EMG analysis ( as interpreted through the root mean square values ) showed that the SJ was performed similarly before and after the training period for the two training groups . However , during the CMJ , only the CTG group adopted a new technique manifested by a short transition phase together with an increase in knee joint stiffness and knee extensor muscle activation and rectus femoris ratio . CONCLUSION It was suggested that the central activities in knee joint during the transition phase , in conjunction with intrinsic muscle contractile properties , play a major role in the regulation of performance during a CMJ . Furthermore , our study suggests that a change in maximal strength and /or explosive strength does not necessarily cause changes in combined movement such as the stretch shortening cycle Objective Introduction of a neuromuscular training program will increase muscle strength , balance , and proprioception in elite female h and ball players . Design Prospect i ve intervention study . Participants Thirty-five female team h and ball players from 2 teams in the elite division participated . Their mean age was 23 ( ±2.5 ) years , and their mean weight was 69.2 ( ±7.3 ) kg . They had played h and ball for 14.9 ( ±3.2 ) years , 4.7 ( ±2.8 ) years at the top level . The total number of training hours per week was 10 to 11 . InterventionBased on earlier studies and knowledge about common risk situations in team h and ball , an anterior cruciate ligament ( ACL ) injury prevention program with 3 different sets of exercises was developed , each set with a 5-step progression from simple to more challenging exercises . The teams were instructed to use the program a minimum of 3 times a week during a training period of 5 to 7 weeks , and then once a week during the season . The duration of each training session was approximately 15 minutes . Main outcome measures Balance ( KAT 2000 ) , proprioception ( threshold to detection of passive motion ) , muscle strength ( Cybex 6000 ) , and 3 functional knee tests . The players were tested pretraining ( test 1 ) and 8 weeks ( test 2 ) and 12 months ( test 3 ) after the training started . Results There was a significant improvement in dynamic balance between test 1 and test 2 , with a balance index ( BI ) of 924 ( ±225 ) and 778 ( ±174 ) , respectively ( P = 0.01 ) . The effect on dynamic balance was maintained 1 year after training ( BI , 730 ± 156 ) . For static balance , no statistically significant changes were found . For the other variables measured , there were no statistical differences during the study period . Conclusion The ACL injury prevention training program improved dynamic balance in an elite team h and ball players Hermassi , S , Chelly , MS , Tabka , Z , Shephard , RJ , and Chamari , K. Effects of 8-week in-season upper and lower limb heavy resistance training on the peak power , throwing velocity , and sprint performance of elite male h and ball players . J Strength Cond Res 25(9 ) : 2424 - 2433 , 2011—The aims of this study were to test the potential of in-season heavy upper and lower limb strength training to enhance peak power output ( Wpeak ) , vertical jump , and h and ball related field performance in elite male h and ball players who were apparently already well trained , and to assess any adverse effects on sprint velocity . Twenty-four competitors were divided r and omly between a heavy resistance ( HR ) group ( age 20 ± 0.7 years ) and a control group ( C ; age 20 ± 0.1 years ) . Resistance training sessions were performed twice a week for 8 weeks . Performance was assessed before and after conditioning . Peak power ( Wpeak ) was determined by cycle ergometer ; vertical squat jump ( SJ ) and countermovement jump ( CMJ ) ; video analyses assessed velocities during the first step ( V1S ) , the first 5 m ( V5 m ) , and between 25 and 30 m ( Vpeak ) of a 30-m sprint . Upper limb bench press and pull-over exercises and lower limb back half squats were performed to 1-repetition maximum ( 1RM ) . Upper limb , leg , and thigh muscle volumes and mean thigh cross-sectional area ( CSA ) were assessed by anthropometry . Wpeak ( W ) for both limbs ( p < 0.001 ) , vertical jump height ( p < 0.01 for both SJ and CMJ ) , 1RM ( p < 0.001 for both upper and lower limbs ) and sprint velocities ( p < 0.01 for V1S and V5 m ; p < 0.001 for Vpeak ) improved in the HR group . Upper body , leg , and thigh muscle volumes and thigh CSA also increased significantly after strength training . We conclude that in-season biweekly heavy back half-squat , pull-over , and bench-press exercises can be commended to elite male h and ball players as improving many measures of h and ball-related performance without adverse effects upon speed of movement Abstract To investigate the influence of adding a weekly eccentric-overload training ( EOT ) session in several athletic performance ’s tests , 18 team-h and ball players were assigned either to an EOT ( n = 11 ) or a Control ( n = 7 ) group . Both groups continued to perform the same habitual strength training , but the EOT group added one session/week during a 7-week training programme consisting of four sets of eight repetitions for the bilateral half-squat and unilateral lunge exercises . The test battery included h and ball throwing velocity , maximum dynamic strength ( 1RM ) , countermovement jump ( CMJ ) , 20 m sprint , triple hop for distance , and eccentric/concentric power in both the half-squat and lunge exercises . Data were analysed using magnitude-based inferences . Both groups improved their 1RM in the half squat , 20 m sprint time , and CMJ performance to a similar extent , but the EOT group showed a beneficial effect for both right [ ( 42/58/0 ) , possibly positive ] and left [ ( 99/1/0 ) , very likely positive ] triple hop for distance performance . In addition , the EOT group showed greater power output improvements in both eccentric and concentric phases of the half-squat ( difference in percent of change ranging from 6.5 % to 22.0 % ) and lunge exercises ( difference in per cent of change ranging from 13.1 % to 24.9 % ) . Nevertheless , no group showed changes in h and ball throwing velocity . Selected variables related to team-h and ball performance ( i.e. functional jumping performance , power output ) can be improved by adding a single EOT session per week , highlighting the usefulness of this low-volume/high-intensity training when aim ing at optimizing dynamic athletic performance Abstract Chelly , MS , Hermassi , S , Aouadi , R , and Shephard , RJ . Effects of 8-week in-season plyometric training on upper and lower limb performance of elite adolescent h and ball players . J Strength Cond Res 28(5 ) : 1401–1410 , 2014—We hypothesized that replacement of a part of the normal in-season regimen of top-level adolescent h and ball players by an 8-week biweekly course of lower and upper limb plyometric training would enhance characteristics important to competition , including peak power output ( Wpeak ) , jump performance , muscle volume , and ball throwing velocity . Study participants ( 23 men , age : 17.4 ± 0.5 years , body mass : 79.9 ± 11.5 kg , height : 1.79 ± 6.19 m , body fat : 13.8 ± 2.1 % ) were r and omly assigned between controls ( C ; n = 11 ) and an experimental group ( E , n = 12 ) . Measures preintervention and postintervention included force-velocity ergometer tests for upper ( Wupper peak ) and lower limbs ( Wlower peak ) , force platform determinations of squat jump ( SJ ) and countermovement jump ( CMJ ) characteristics ( jump height , maximal force , initial velocity , and average power ) , video filming of sprint velocities ( first step [ V1S ] , first 5 m [ V5 m ] , and 25–30 m [ Vmax ] ) , and anthropometric estimates of leg muscle volume . E showed gains relative to C in Wupper peak and Wlower peak ( p < 0.01 and p < 0.001 ) , SJ ( height p < 0.01 ; force p ⩽ 0.05 ) , CMJ ( height p < 0.01 ; force p < 0.01 and relative power p ⩽ 0.05 ) , and sprint velocities ( p < 0.001 for V1S , V5 m , and Vmax ) . E also showed increases in leg and thigh muscle volumes ( p < 0.001 ) , but arm muscle volumes did not differ from control . We conclude that introduction of biweekly plyometric training into the st and ard regimen improved components important to h and ball performance , particularly explosive actions , such as sprinting , jumping , and ball throwing velocity Abstract . Maximal concentric one repetition maximum half-squat ( 1RMHS ) , bench-press ( 1RMBP ) , power-load curves during concentric actions with loads ranging from 30 % to 100 % of 1RMHS and 1RMBP were examined in 70 male subjects divided into five groups : weightlifters ( WL , n=11 ) , h and ball players ( HP , n=19 ) , amateur road cyclists ( RC , n=18 ) , middle-distance runners ( MDR , n=10 ) and age-matched control subjects ( C , n=12 ) . The 1RMHS values in WL , HP and RC were 50 % , 29 % and 28 % greater , respectively , ( P<0.001–0.01 ) than those recorded for MDR and C. The half-squat average power outputs at all loads examined ( from 30 % to 100 % ) in WL and HP ( P<0.001 at 45 % and 60 % with HP ) were higher ( P<0.05–0.001 ) than those in MDR , RC and C. Average power output at the load of 30 % of 1RMHS in RC was higher ( P<0.05 ) than that recorded in MDR and C. Maximal power output was produced at the load of 60 % for HP , MDR and C , and at the load of 45 % for WL and RC . The 1RMBP in WL was larger ( P<0.05 ) than those recorded in HP , RC , MDR and C. In the bench press , average muscle power outputs in WL and HP were higher ( P<0.05–0.001 ) than those in MDR , RC and C , and were maximized at a load of 30 % of 1RM for WL and HP , and at 45 % for RC , MDR and C. In addition , the velocities that elicited the maximal power in the lower extremities were lower ( ≈0.75 m·s–1 ) than those occurring in the upper extremities ( ≈1 m·s–1 ) . The data suggest that the magnitude of the sport-related differences in strength and /or muscle power output may be explained in part by differences in muscle cross-sectional area , fibre type distribution and in the muscle mechanics of the upper and lower limbs as well as by training background Abstract Ignjatovic , AM , Markovic , ZM , and Radovanovic , DS . Effects of 12-week medicine ball training on muscle strength and power in young female h and ball players . J Strength Cond Res 26(8 ) : 2166–2173 , 2012—The purpose of this study was to examine the effects of medicine ball training on the strength and power in young female h and ball athletes . Twenty-one young female h and ball players ( age , 16.9 ± 1.2 years ) were r and omly assigned to experimental and control groups . Experimental group ( n = 11 ) participated in a 12-week medicine ball training program incorporated into the regular training session , whereas controls ( n = 10 ) participated only in the regular training . Performance in the medicine ball throws in st and ing and sitting positions , 1 repetition maximum ( 1RM ) bench and shoulder press , and power test at 2 different loads ( 30 and 50 % of 1RM ) on bench and shoulder press were assessed at pre- and posttraining testing . The athletes participating in the medicine ball training program made significantly greater gains in all medicine ball throw tests compared with the controls ( p < 0.01 ) . Also , the experimental group made significantly greater gains in bench and shoulder press power than control group ( p < 0.05 ) . Both training groups ( E ) and ( C ) significantly ( p < 0.05 ) increased 1RM bench and shoulder strength , with no differences observed between the groups . Additionally , medicine ball throw tests showed stronger correlation with power tests , than with 1RM tests . These data suggest that 12-week medicine ball training , when incorporated into a regular training session , can provide greater sport-specific training improvements in the upper body for young female h and ball players Abstract Hermassi , S , van den Tillaar , R , Khlifa , R , Chelly , MS , and Chamari , K. Comparison of in-season-specific resistance vs. a regular throwing training program on throwing velocity , anthropometry , and power performance in elite h and ball players . J Strength Cond Res 29(8 ) : 2105–2114 , 2015—The purpose of this study was to compare the effect of a specific resistance training program ( throwing movement with a medicine ball ) with that of regular training ( throwing with regular balls ) on ball velocity , anthropometry , maximal upper-body strength , and power . Thirty-four elite male team h and ball players ( age : 18 ± 0.5 years , body mass : 80.6 ± 5.5 kg , height : 1.80 ± 5.1 m , body fat : 13.4 ± 0.6 % ) were r and omly assigned to 1 of the 3 groups : control ( n = 10 ) , resistance training group ( n = 12 ) , or regular throwing training group ( n = 12 ) . Over the 8-week in season , the athletes performed 3 times per week according to an assigned training program alongside their normal team h and ball training . One repetition maximum ( 1RM ) bench press and 1RM pullover scores assessed maximal arm strength . Anthropometry was assessed by body mass , fat percentage , and muscle volumes of upper body . H and ball throwing velocity was measured by a st and ing throw , a throw with run , and a jump throw . Power was measured by measuring total distance thrown by a 3-kg medicine ball overhead throw . Throwing ball velocity , maximal strength , power , and muscle volume increases for the specific resistance training group after the 8 weeks of training , whereas only maximal strength , muscle volume and power and in the jump throw increases were found for the regular throwing training group . No significant changes for the control group were found . The current findings suggest that elite male h and ball players can improve ball velocity , anthropometrics , maximal upper-body strength , and power during the competition season by implementing a medicine ball throwing program |
542 | 29,270,698 | Conclusions Goshajinkigan tended to prevent persistence but not severity of CIPN . | Background Chemotherapy-induced peripheral neuropathy ( CIPN ) is common and presents with persistent and challenging symptoms for which there is no effective means of prevention .
This systematic review assessed the efficacy and safety of Goshajinkigan in the prevention of CIPN . | Purpose Oxaliplatin-induced peripheral neurotoxicity ( OPN ) is frequent and potentially severe , but successful treatment of this condition is still an unmet clinical need . We aim ed to determine whether treatment with goshajinkigan ( TJ-107 ) , a traditional Japanese medicine , is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with st and ard FOLFOX regimens . Methods In this phase 2 , r and omized , double-blind , placebo-controlled study , patients undergoing oxaliplatin-based chemotherapy were r and omized to receive either oral TJ-107 ( 7.5 g ) or matching placebo daily . The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline , every 2 weeks until the 8th cycle , and every 4 weeks thereafter until the 26th week . The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy . Results Analyses were done by intention to treat . Eighty-nine patients were r and omly assigned to receive either TJ-107 ( n = 44 ) or placebo ( n = 45 ) between May 2009 and March 2010 . The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups , respectively ( relative risk ( RR ) , 0.76 ; 95 % CI , 0.47–1.21 ) . The incidence of grade 3 OPN was 7 % ( TJ-107 ) vs. 13 % ( placebo ) ( 0.51 , 0.14–1.92 ) . No concerns regarding toxicity emerged with TJ-107 treatment . Conclusions TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy IMPORTANCE There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy . OBJECTIVE To determine the effect of duloxetine , 60 mg daily , on average pain severity . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic setting s between April 2008 and March 2011 . Study follow-up was completed July 2012 . Stratified by chemotherapeutic drug and comorbid pain risk , patients were r and omized to receive either duloxetine followed by placebo or placebo followed by duloxetine . Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10 , representing average chemotherapy-induced pain , after paclitaxel , other taxane , or oxaliplatin treatment . INTERVENTIONS The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks . MAIN OUTCOME MEASURES The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain . Pain severity was assessed using the Brief Pain Inventory-Short Form " average pain " item with 0 representing no pain and 10 representing as bad as can be imagined . RESULTS Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 ( 95 % CI , 0.72 - 1.40 ) vs 0.34 ( 95 % CI , 0.01 - 0.66 ) among those who received placebo ( P = .003 ; effect size , 0.513 ) . The observed mean difference in the average pain score between duloxetine and placebo was 0.73 ( 95 % CI , 0.26 - 1.20 ) . Fifty-nine percent of those initially receiving duloxetine vs 38 % of those initially receiving placebo reported decreased pain of any amount . CONCLUSION AND RELEVANCE Among patients with painful chemotherapy-induced peripheral neuropathy , the use of duloxetine compared with placebo for 5 weeks result ed in a greater reduction in pain . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00489411 Background Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy . Calcium and magnesium ( Ca/Mg ) infusions are frequently used as preventatives , but a recent phase III trial failed to show that they prevent neurotoxicity . We therefore conducted a multicenter r and omized phase III trial to compare fluorouracil , leucovorin , and oxaliplatin ( mFOLFOX6 ) with and without Goshajinkigan ( GJG ) , a traditional Japanese herbal medicine ( Kampo ) , to determine GJG ’s potential for reducing peripheral neuropathy in patients with colorectal cancer . Methods Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were r and omly assigned to GJG ( 7.5 mg three times daily ) or placebo in a double-blind manner . The primary endpoint was the time to grade 2 or greater neuropathy , which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI CTCAE ) . Findings An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued . One hundred eighty-two patients were evaluable for response . They included 89 patients in the GJG group and 93 patients in the placebo group . The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group . A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy ( hazard ratio , 1.908 ; p = 0.007 ) . Conclusion Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial . The clinical study was therefore terminated IMPORTANCE Chemotherapy-induced peripheral neuropathy ( CIPN ) is a common adverse effect of neurotoxic chemotherapy result ing in pain , sensory loss , and decreased quality of life . Few studies have prospect ively examined the relationship between sensory neuropathy symptoms , falls , and fall-related injuries for patients receiving neurotoxic chemotherapy . OBJECTIVE To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy . DESIGN , SETTING , AND PARTICIPANTS In this secondary analysis of a prospect i ve study , 116 patients with breast , ovarian , or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics . These patients would call a novel automated telephone system daily for 1 full course of chemotherapy . The telephone system ( SymptomCare@Home ) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a question naire about falls . Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not . Data analysis was performed in November 2015 . EXPOSURE Chemotherapy with a neurotoxic taxane or platinum agent . MAIN OUTCOMES AND MEASURES Patient-reported falls or near falls and fall-related injuries . The hypothesis was generated after data collection but prior to data analysis . RESULTS Of the 116 patients who started neurotoxic chemotherapy ( mean [ SD ] age was 55.5 [ 11.9 ] years , and 109 [ 94.0 % ] were female ) , 32 met the predetermined criteria for CIPN symptoms . The mean duration of follow-up was 62 days , with 51 telephone calls completed per participant . Seventy-four falls or near falls were reported . The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms ( hazard ratio , 2.67 [ 95 % CI , 1.62 - 4.41 ] ; P < .001 ) . The participants with CIPN symptoms were more likely than the participants without CIPN symptoms to obtain medical care for falls ( 8 of 32 participants with CIPN symptoms [ 25.0 % ] vs 6 of 84 participants without CIPN symptoms [ 7.1 % ] ; P = .01 ) . CONCLUSIONS AND RELEVANCE These findings suggest that the sensory symptoms of CIPN are an indicator of an increased risk of falling and an increased use of health care re sources . This study demonstrates the utility of a novel telephone-based system to track neuropathy symptoms . Careful monitoring and coaching of patients receiving neurotoxic chemotherapy for new sensory symptoms may facilitate more effective fall prevention strategies Goshajinkigan , a herbal medicine , has long been used in Japan to alleviate the subjective symptoms of diabetic neuropathy ; however , its effects have not been confirmed objective ly . We evaluated its effects on subjective symptoms and on vibration sensation in patients with diabetic neuropathy . The oral administration of 7.5 g/day of Goshajinkigan for 3 months ( treatment period ) relieved subjective symptoms of numbness in 9 of 13 patients . When the drug was discontinued for 2 months as a washout period , the subjective symptom worsened in 7 of 13 patients . Chi-square analysis revealed significant effects of Goshajiniagan on subjective symptoms ( P < 0.001 for numbness and P < 0.05 for cold sensation ) . Vibration sensation was evaluated by measuring vibratory threshold using an SMV-5 vibrometer . There were significant changes in vibratory thresholds by paired t-test ( P < 0.05 ) both in the upper and the lower extremities during the treatment and washout periods . Chi-square analysis also revealed a significant effect of Goshajinkigan on vibratory threshold ( P < 0.01 ) . There was no significant change in glycosylated hemoglobin as a whole during the study . These observations confirm that Goshajinkigan relieves subjective symptoms and demonstrate that it improves vibration sensation in patients with diabetic neuropathy BACKGROUND Goshajinkigan ( GJG ) is used for the treatment of several neurological symptoms . We investigated the efficacy of GJG and mecobalamin ( B12 ) against neurotoxicity associated with docetaxel ( DOC ) in breast cancer patients . MATERIAL S AND METHODS Sixty breast cancer patients were treated with DOC . Thirty-three patients ( GJG group ) received oral administration of 7.5 g/day GJG and 27 patients ( B12 group ) received oral administration of 1500 μg/day B12 . Neuropathy was evaluated according to DEB-NTC ( Neurotoxicity Criteria of Debiopharm ) , Common Terminology Criteria for Adverse Events ( NCI-CTC ) ver . 3.0 , and a visual analogue scale ( VAS ) . This study employed a r and omized open design . RESULTS The incidence of neuropathy was 39.3 % in the GJG group , and 88.9 % in the B12 group ( p<0.01 ) . In the GJG group , grade 1 DEB-NTC was observed in 2 cases , grade 2 in 5 cases and grade 3 in 5 cases . Grade 1 NCI-CTC was observed in 7 cases , grade 2 in 6 cases , and VAS was 2.7 ± 2.2 . In the B12 group , grade s 1 , 2 and 3 DEB-NTC were observed in one case , 12 cases and 12 cases , respectively ; and grade s 1 , 2 and 3 NCI-CTC were observed in 11 cases , 12 cases and one case , and VAS was 4.9 ± 2.4 . CONCLUSIONS Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen |
543 | 23,550,773 | HLA-matched PLTs did not reduce alloimmunization and refractoriness rates beyond that offered by leukoreduction , and utilization was not consistently improved .
HLA-matched PLTs led to better 1-hour posttransfusion count increments and percentage of PLT recovery in refractory patients ; however , the effect at 24 hours was inconsistent . | BACKGROUND HLA-matched platelets ( PLTs ) are widely used to transfuse patients but the effectiveness of HLA matching has not been well defined and the cost is approximately five times the cost of preparing the r and om-donor PLTs .
The objective of this systematic review was to determine whether HLA-matched PLTs lead to a reduction in mortality ; reduction in frequency or severity of hemorrhage ; reduction in HLA alloimmunization , refractoriness , or PLT utilization ; or improvement in PLT count increment in patients with hypoproliferative thrombocytopenia . | Alloantibodies against HLA antigens can be reduced by applying leukodepletion to transfusions . Because the importance of immunological and nonimmunological causes of poor platelet transfusion results using leukodepleted transfusions is not clear , we conducted a prospect i ve study in an unselected patient population receiving leukodepleted transfusions . In 97 patients with hematological malignancies , 181 r and om leukodepleted platelet transfusions were studied for immunological causes of poor platelet transfusion results by calculating the odds ratio of four different screening tests for a low platelet recovery . Nonimmune causes were also studied by calculating the odds ratio of the most prevalent nonimmune causes for a low platelet recovery . No single screening test showed an association with recovery after 1 and 16 h following a platelet transfusion . The combination of a positive enzyme-linked immunosorbent assay ( ELISA ) and platelet immunofluorescence test ( PIFT ) or a combination of a positive lymphocyte immunofluorescence test ( LIFT ) and PIFT , demonstrating an association with a low platelet recovery after 16 h , was present in 2 % of all platelet transfusions . Of nonimmune causes , splenomegaly and storage time of platelets for more than 3 days were associated with low platelet recovery after 1 h and 16 h of being present in 29 % and 47 % of all platelet transfusions , respectively . Immunological causes account for a small proportion of poor platelet transfusion results compared to nonimmunological causes in a nonselected patient population receiving leukodepleted transfusions Seventy-nine platelet transfusions to 73 thrombocytopenic patients with cancer were analyzed to determine whether a platelet count obtained one hour after transfusion could help differentiate between alloimmunization and other clinical factors that result in rapid platelet destruction . These transfusions were selected because 18- to 24-hour increments were inadequate in response to fresh , r and om donor platelets . A corrected count increment ( Cl ) ( Cl=[posttransfusion count-pretransfusion count]Xbody surface area [ sq m]/platelets transfusedX10 ' ' ) at one hour of 10X103/microliter or greater was associated with absence of lymphocytotoxic antibody , whereas increments of less than 10X103/microliter were generally associated with high levels of strongly cytotoxic antibody . HLA-matched transfusions produced no improvement in increments when the previous one-hour Cl had been 10X103/microliter or greater , whereas in the other group significantly better increments were obtained . A one-hour posttransfusion count is a simple test that correlates well with the presence of antibody against HLA antigens , is valuable in predicting the need for HLA-matched platelets , and helps avoid wasteful , empirical use of such transfusions Immune and nonimmune causes of platelet refractoriness were evaluated in a group of patients receiving HLA‐selected single‐donor platelet transfusions . During a 1‐year observation period , 1 h and 24 h platelet recoveries were determined after 522 single‐donor platelet transfusions given to 43 patients persistently refractory to pooled r and om‐donor platelet transfusions . 72 % of patients tested ultimately developed lymphocytotoxic antibodies suggesting they were alloimmunized . When significant lymphocytotoxic antibodies were demonstrable in these patients , HLA well‐matched platelet transfusions consistently produced good transfusion responses . In contrast , patients without lymphocytotoxic antibodies had clinical factors that adversely affected transfusion outcome ( P < 0.0001 ) . Fever and splenomegaly markedly reduced 1 h post‐transfusion platelet recoveries , while sepsis compromised the 24 h platelet recovery . Overall , the presence of any clinical factor was most likely to reduce 1 h platelet recovery , while donor‐recipient HLA incompatibilities correlated best with poor 24 h posttransfusion platelet recovery A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets ( TRAP ) . Responses measured were platelet increments , interval between platelet transfusions , and platelet refractoriness . Patient factors that improved platelet responses were splenectomy and increasing patient age . In contrast , at least 2 prior pregnancies , male gender , splenomegaly , bleeding , fever , infection , disseminated intravascular coagulation , increasing height and weight , lymphocytotoxic antibody positivity , an increasing number of platelet transfusions , or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses . Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets , platelets stored for 48 hours or less , and giving large doses of platelets while ultraviolet B ( UV-B ) or gamma irradiation decreased platelet responses . However , in alloimmunized lymphocytoxic antibody-positive patients , the immediate increment to UV-B-irradiated platelets was well maintained , whereas all other products showed substantial reductions . Refractoriness to platelet transfusions developed in 27 % of the patients . Platelet refractoriness was associated with lymphocytotoxic antibody positivity , heparin administration , fever , bleeding , increasing number of platelet transfusions , increasing weight , at least 2 pregnancies , and male gender . The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets R and omized controlled trials have shown a reduction in platelet alloimmunization and refractoriness in patients with acute leukemia ( AL ) with the use of poststorage leukoreduction of blood products . Universal prestorage leukoreduction ( ULR ) of red cell and platelet products has been performed in Canada since August 1999 . We conducted a retrospective analysis of 13 902 platelet transfusions in 617 patients undergoing chemotherapy ( CT ) for AL or stem cell transplantation ( SCT ) before ( n = 315 ) and after ( n = 302 ) the introduction of ULR . Alloimmunization was significantly reduced ( 19 % to 7 % , P < .001 ) in the post-ULR group . Alloimmune platelet refractoriness was similarly reduced ( 14 % to 4 % , P < .001 ) . Fewer patients in the post-ULR group received HLA-matched platelets ( 14 % vs 5 % , P < .001 ) . Alloimmunization and alloimmune refractoriness in the 318 patients who were previously pregnant and /or transfused were also reduced after ULR ( P = .023 and P = .005 , respectively ) . In a Cox regression model , the 3 independent factors that predicted for alloimmune refractoriness were nonleukoreduced blood products ( relative risk [ RR ] , 2.2 [ 95 % CI , 1.2 - 4.3 ] ) , a history of pregnancy and /or transfusion ( RR , 2.3 [ 95 % CI , 1.3 - 4.2 ] ) , and receipt of 13 or more platelet transfusions ( RR , 6.0 [ 95 % CI , 2.4 - 15.3 ] ) . In conclusion , ULR reduces alloimmunization , refractoriness , and requirements for HLA-matched platelets when applied as routine transfusion practice to patients receiving CT or SCT A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized , thrombocytopenic patients is the large pool of HL‐typed donors needed to procure platelets perfectly matched for HLA antigens . We have , therefore , investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility . In 421 transfusions administered to 59 alloimmunized patients who were refractory to “ r and om donor ” platelets , it was found that platelets mismatched for 1 or 2 “ cross‐reactive ” HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets . A significant number of patients also responded to platelets from donors selectively mismatched for non‐cross‐reactive HLA antigens . The latter group had a significantly reduced frequency of the antigen HLA‐A2 ( 13 % ) in comparison to the total patient population ( 49 % ) . Use of donors whose HLA antigens are serologically cross‐reactive with those of alloimmunized patients provides approximately 10 times as many prospect i ve donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients Alloantibody tests demonstrate immunological causes of insufficient increments in r and om platelet transfusions . The value of a positive or negative test result in predicting the outcome of human leucocyte antigen (HLA)‐matched transfusions in patients refractory to leucodepleted r and om platelet transfusions has not been assessed . We retrospectively evaluated the outcome of the first HLA‐matched platelet transfusion in 72 patients with haematological diseases in two ways : first , the strategy according to which the patient was selected for HLA‐matched platelet transfusions was analysed . The strategies were : ( i ) results of alloantibody tests were not available , ( ii ) a positive alloantibody test , ( iii ) a negative alloantibody test . Secondly , the outcome of the first HLA‐matched transfusion was investigated relative to the results of alloantibody tests , irrespective of the decision strategy . No significant association was found between the decision strategy and the outcome of the first HLA‐matched platelet transfusion . Positive alloantibody tests , however , predicted a better outcome of the first HLA‐matched platelet transfusion ( P = 0·04 and P = 0·03 after 1 and 16 h respectively ) . In patients refractory to r and om platelet transfusions , positive alloantibody tests predicted a better outcome of HLA‐matched platelet transfusions . Patients with negative alloantibody tests , however , may benefit from HLA‐matched platelet transfusions Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Repeated platelet transfusion to thrombocytopenic patients frequently induce anti HLA antibodies , which are responsible for transfusion refractoriness . As the transfused platelet suspensions usually contain 15 - 30 % of the leukocytes originally present in the blood , it is not known whether these antibodies are raised by the platelets or by the contaminating leukocytes in the platelet suspensions . In the mouse , pure platelet suspensions are not able to induce a primary antibody response , as measured by the NIH test and the indirect immunofluorescence test on platelets and leukocytes , despite repeated injections . However , when the platelet suspensions are contaminated with leukocytes ( 10(3 ) or more/injection ) an antibody response is induced . This response is higher than the response indiced by an equal amount of leukocytes alone . As in man the use of leukocyte poor platelets postpones the development of refractoriness to r and om platelets it is concluded that transfusions with leukocyte free platelets will probably prevent immunization against the HLA antigens This study describes a novel application of HLAMatchmaker to determine platelet compatibility in 16 alloimmunized patients with aplastic anemia refractory to r and om donor platelet transfusions . HLAMatchmaker is a software algorithm that predicts HLA compatibility by identifying immunogenic epitopes represented by amino acid triplets in antibody-accessible regions of human leukocyte antigen ( HLA ) molecules and determines the number of triplet mismatches ( TMMs ) and highly immunogenic triplet mismatches ( HIMMs ) . Corrected count increments ( CCIs ) and molecular HLA typing were available for 523 transfusions . Conventional compatibility assessment based on cross-reactive group ( CREG ) determination was not predictive of transfusion outcome . Low HIMMs and TMMs numbers were associated with a higher likelihood of satisfactory ( CCIs > or = 8) compared with unsatisfactory ( CCIs < 8) outcomes ( median HIMMs = 4 vs 6 , p2 value < .001 ; median TMMs = 11 vs 13 , p2 value < .001 ) . Although receiver operator characteristic curves revealed that HIMMs or TMMs number are not powerful predictors of individual transfusion outcome , a threshold of at least 3 HIMMs or at least 9 TMMs appeared to be associated with successful transfusions . Triplet-matched transfusions were successful , regardless of CREG matching . Our data vali date HLAMatchmaker for platelet transfusions and demonstrate its potential to refine and exp and donor selection for HLA-alloimmunized patients We implemented a prospect i ve study to evaluate platelet transfusion utilization , re source use , and costs in a tertiary care hospital over a 6‐month period . All hospitalized patients receiving platelet transfusions between July and December 1996 were followed prospect ively to determine platelet use and costs . Clinical and financial data were collected , evaluated , and compared to identify trends in re source utilization based on admitting service and platelet‐refractory status . One thous and nine hundred forty‐four platelet units were transfused to 245 hospitalized patients ( 50.6 % male , mean age 49 years ) during the study period . The majority of platelet units transfused were single donor ( N = 1,460 , 75 % ) and administered to bone marrow patients and patients with a hematological malignancy/disorder . Median hospitalization costs per admission were $ 27,750 , ranging from a high of $ 58,729 for admission to the Bone Marrow Transplant service to $ 13,856 per admission to the Internal Medicine/Other service . Patients were refractory to platelet transfusions during 21.6 % of hospitalizations . Hospital stays were longer ( 35.0 days vs. 14.4 days , P < 0.001 ) and inpatient hospital costs ( $ 103,956 vs. $ 37,817 , P < 0.001 ) were more than two and a half times higher for patients refractory to platelet transfusions . Platelet utilization , re source use , and costs vary by admitting service . Refractoriness to platelet transfusion was associated with significantly greater costs and lengths of stay . Monitoring platelet transfusion practice s , particularly for patients refractory to platelet transfusions , may be beneficial for limiting costs and improving efficacy . Am . J. Hematol . 64:251–256 , 2000 . © 2000 Wiley‐Liss , BACKGROUND Immune refractoriness to platelet ( PLT ) transfusion is primarily due to HLA antibody . Patients at our institution are identified as refractory due to HLA by a Luminex-based immunoglobulin (Ig)G-single-antigen-bead ( SAB ) assay , but in highly sensitized patients , antigen-negative compatible donors can not be found due to the high sensitivity of the IgG-SAB method . We developed an assay that detects only HLA antibodies binding the first complement component ( C1q ) . We hypothesized that the C1q-SAB method might be more relevant than the IgG-SAB method because the antibodies identified may activate the complement cascade causing PLT destruction . STUDY DESIGN AND METHODS Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG-SAB method . They were retrospectively retested by the C1q-SAB method . Calculated percent reactive antibody ( CPRA ) and HLA antibody specificities were compared between the two methods and corrected count increment ( CCI ) values were analyzed . Additionally the impact of ABO compatibility on CCI responses was evaluated . RESULTS The mean CPRA value was significantly lower by C1q-SAB ( 60 % ) than by IgG-SAB ( 94 % ; p < 0.05 ) . Patients showed significantly better CCI ( 10.6 × 10(9 ) ± 0.8 × 10(9 ) /L ) with C1q-compatible ( n = 134 ) than with C1q-incompatible PLTs ( n = 43 ) ( 2.5 × 10(9 ) ± 0.9 × 10(9 ) /L/m(2 ) ; p < 0.0001 ) . ABO compatibility did not significantly impact the CCI values ( p < 0.0001 ) . Our results show that 75 % of PLT units previously considered incompatible were actually compatible . CONCLUSION For highly refractory patients to PLT transfusion , the C1q-based SAB binding assay may be a better method for identifying clinical ly relevant HLA antibodies and selecting PLT units that will result in acceptable CCI Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens ( HLA ) , with result ant refractoriness to platelet transfusions . Autologous peripheral blood or bone marrow stem cell transplantation ( referred here collectively as ‘ autoBMT ’ ) is emerging as a st and ard consolidative strategy in acute myelogenous leukemia ( AML ) . We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT ; we therefore retrospectively analyzed 39 AML patients for this complication following BMT . All patients received high-dose chemoradiotherapy , followed by infusion of allogeneic sibling donor ( n = 12 , alloBMT ) or autologous ( n = 27 , autoBMT ) stem cells . HLA alloimmunization was assessed if patients were suspected of immune refractoriness to r and om donor platelet transfusions . Within 100 days of stem cell infusion , one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized ( not statistically significant , NS ) . Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding , which contributed to their demise while still in remission ( P < 0.001 ) . increased platelet requirements in hla alloimmunized autobmt recipients were observed between days 61 and 100 post-bmt , at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients ( P < 0.01 ) and 17 in allobmt patients . our data suggest that platelet transfusion refractoriness , when associated with hla alloimmunization , is a risk factor for increased platelet transfusion requirements , delayed bleeding , and poor outcome following autobmt for aml . Bone Marrow Transplantation ( 2000 ) 26 , 315–320 A multi-site clinical study compared platelets chosen for refractory patients by prospect i ve platelet crossmatching using stored donor platelets and HLA-based selection . Seventy-three patients who were refractory to r and om-donor platelets received two plateletpheresis components , one chosen by HLA-based criteria and the other by crossmatching . Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results . Each of the five study sites used a crossmatch procedure with which it had experience . Results from this study indicate the following : 1 ) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grade s of matching and mismatching was compared to a crossmatch-based method of donor selection . 2 ) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone . Donor selection based on HLA matching ( grade s A or BU ) was also superior to selection based on any degree of HLA mismatching ( grade s BX , C , or D ) . 3 ) Selection of donors based on HLA-cross-reactive groups ( defined by in vitro serologic crossreactivity ) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone . 4 ) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients , even though patients demonstrating nonimmune factors were eliminated from the study . It can be concluded that HLA-compatible ( grade s A and BU ) platelets provide optimal support for refractory patients , but that crossmatch-selected platelets are acceptable as an alternative component Effective platelet support for alloimmunized refractory thrombocytopenic patients may be provided by several potential strategies , the most common being HLA-matched single-donor platelets or crossmatch-compatible , pooled r and om- or single-donor platelets . This study used a detailed economic analysis to compare the cost-effectiveness of several techniques for platelet crossmatching and that of HLA-matched single-donor platelets . The crossmatch methods evaluated were a microlymphocytotoxicity test ( LCT ) , an immunofluorescence technique ( PSIFT ) , a radioactive antiglobulin test ( PRAT ) , and an enzyme-linked immunosorbent assay ( ELISA ) . The analysis was based on the need to support 100 refractory patients with acute leukemia with a presumed requirement of 500 transfusions . The relative costs for a successful crossmatch were : PRAT less than LCT less than LCT + PRAT less than PSIFT less than ELISA . In the comparison of the crossmatch methods , an increase in costs was generally associated with an increase in the number of successful transfusion episodes . However , decreasing marginal gains were seen . The HLA-matched single-donor platelets were relatively cost-inefficient in comparison to the crossmatch-compatible platelets . A theoretic sequence of tests for cost-effective provision of optimal platelet support in refractory patients was evaluated . Such considerations of cost are important in the selection of an optimal program for the management of alloimmunized refractory thrombocytopenic patients Immune-mediated refractoriness to platelet transfusion is a major problem in patients undergoing HSCT . In a cohort of 50 pediatric patients affected by beta thalassemia coming from Middle East countries , we experienced a high incidence of refractoriness because of anti-HLA antibodies during post-HSCT aplasia . In a risk factors analysis , factors predicting a negative transfusion outcome were presence of spleen and the number of anti-HLA antibodies . We adopted a policy to select platelet donors by avoiding HLA antigens against which the patient had specific antibodies . Transfusion of dedicated units result ed in 26 % refractoriness compared to 74 % to r and om units ( p < 0.0001 ) . When dedicated transfusions were used , the presence of spleen did not influence transfusion outcome . Analyzing transfusion outcome depending on the degree of HLA match and ABO compatibility , 76 % successful transfusions were obtained with HLA-matched- ABO compatible followed by 67 % in HLA-1mismatch- ABO compatible or HLA-matched- ABO incompatible and by 46 % in HLA-1mismatch- ABO incompatible . In conclusion , we provide evidence that the selection of platelet donors according to patient characteristics , anti-HLA antibodies and ABO matching , is successful in reducing platelet refractoriness in heavily alloimmunized thalassemia patients undergoing transplantation Histocompatibility ( HLA ) matched platelet concentrates , harvested from voluntary donors by plateletpheresis using blood cell separators , were used in the treatment of 14 thrombocytopenic patients who had become unresponsive to the transfusion of r and om platelet concentrates . In all patients bleeding stopped . Platelet concentrates contained a mean of 3.56 X 10(11 ) platelets/l . The average increase in platelet count was 33 X 10(9)/l . The use of HLA matched platelet transfusions should be considered in bleeding thrombocytopenic patients refractory to the transfusion of r and om platelets BACKGROUND Although HLA-matched platelets are frequently requested for alloimmunized patients , recent evidence has indicated that 1-hour posttransfusion platelet increments in these patients are specifically sensitive to crossmatch compatibility . STUDY DESIGN AND METHODS To determine the extent of advantage gained by use of single-donor apheresis ( SD ) platelets selected on the basis of HLA match when crossmatch-compatible SD platelets were available , a total of 220 platelet transfusions given in the absence of individually determined significant nonimmune factors were analyzed in a well-characterized cohort of platelet-refractory patients . Platelets were selected by solid-phase crossmatch from a small donor pool of relatively poor HLA matches or , upon request , ordered as HLA-matched and later crossmatched . RESULTS Alloimmunized patients responded better to SD platelets selected on the basis of HLA than to pooled platelet concentrates or SD platelets selected at r and om , although most of the benefit was limited to the 57-percent subset of good HLA matches . Crossmatch-compatible SD platelets provided similar posttransfusion platelet increments independent of the HLA match . None of 31 crossmatch-incompatible SD platelets transfused provided an adequate increment , including 13 that were ordered as HLA-matched platelets . CONCLUSION No benefit could be demonstrated from requesting that SD platelets be HLA-matched when crossmatch-compatible SD platelets were available BACKGROUND Despite supportive care with platelet ( PLT ) transfusions , bleeding complications occur in a substantial number of patients with thrombocytopenia due to cytotoxic therapy . Moreover , refractoriness to PLT transfusions remains a frequently encountered problem . The clinical impact of PLT transfusion failure was investigated in 117 patients , part of a r and omized PLT transfusion trial , which excluded patients with HLA and /or HPA alloantibodies . STUDY DESIGN AND METHODS Between October 2003 and April 2005 , a multicenter r and omized controlled trial , testing the clinical efficacy of PLTs stored in plasma compared to PLT additive solution ( PAS II ) , was performed . Using multiple regression analysis of observational data of patients r and omized in one of the participating centers , the occurrence of PLT transfusion refractoriness was analyzed for a relation with bleeding complications and patient survival . RESULTS PLT transfusion failure occurred at least once in 49.6 percent of the patients . Mild to moderate bleeding complications occurred in 19 percent of the patients . PLT transfusion failure was , independently from thrombocytopenia , positively associated with bleeding complications ( odds ratio , 3.4 ; 95 % confidence interval , 1.1 - 11 ) . Moreover , patients experiencing one or more 24-hour PLT transfusion failures had , compared to patients always showing a sufficient 24-hour increment , a significantly reduced median survival of 491 days ( interquartile range [ IQR ] , 156 - 858 days ) versus 825 days ( IQR , 355 - 996 days ) , respectively . In a Cox regression model , the effect on survival was independent of therapy , diagnosis , and age . CONCLUSION Our results suggest that PLT transfusion failure might be a sensitive clinical marker for the occurrence of bleeding and impaired patient survival . PLT transfusion failure , bleeding complications , and decreased survival could be manifestations of a more severe degree of endothelial damage Abstract Thrombocytopenic patients who are refractory to transfusions of platelets obtained from r and om donors will respond to platelets from HL-A-identical siblings . The efficacy of using HL-A lymphocyte typing to select unrelated compatible platelet donors , however , has not been well documented . In this study , three patients who were not responding to r and om donor platelets were transfused with platelets obtained from selected unrelated persons matched for HL-A. The median response in circulating platelets ( increment times body-surface area per unit ) measured at 20 hours was 11.2 , 9.1 and 17.0 ( X 103 ) as compared to 0 , 0 and 2.2 ( X 103 ) , respectively , to nonmatched platelets . These observations indicate that alloimmunization in multi-transfused patients is primarily due to HL-A antigens and that lymphocyte HL-A typing can be used to select unrelated compatible platelet donors for refractory patients BACKGROUND Patients who are refractory to platelet transfusion as a result of HLA alloimmunization are generally given HLA-matched or crossmatched platelets . However , HLA-matched platelets that are matched at HLA-A and -B loci ( A-matched ) or those without any mismatched or cross-reactive antigens ( BU-matched ) are frequently unavailable . A disadvantage of crossmatching is that crossmatched platelets have a shelf life of only 5 days , so that crossmatch tests must be performed frequently for patients requiring long-term platelet transfusions . An alternative method is the selection of platelets according to the patient 's HLA antibody specificity , called the antibody specificity prediction ( ASP ) method . STUDY DESIGN AND METHODS An anti-human globulin-enhanced microlymphocytotoxicity test modified by a double addition of serum and a computer program were used to determine the specificity of patients ' HLA antibodies . Platelet crossmatching was performed with a solid-phase adherence assay . The percentage of platelet recovery ( PPR ) was determined in 1621 platelet transfusions in an observational study in 114 patients , and the PPR of platelets selected by the ASP method was compared with the PPR of those that were HLA-matched , crossmatched , or r and omly selected . The numbers of potential donors in files of HLA-typed donors as identified by HLA matching vs. the ASP method were determined . RESULTS After adjustments for covariates , the mean + /- SEM PPR was similar for HLA-matched ( 21 + /-4 % ) , cross-matched ( 23+/-4 % ) , and ASP-selected ( 24+/-3 % ) platelets and was significantly lower for r and omly selected ( 15+/-1.4 % ) platelets . For 29 alloimmunized HLA-typed patients , the mean number of potential donors found in a file of 7247 HLA-typed donors was 6 who were an HLA-A match ( median = 1 ) , 33 who were an HLA-BU match ( median = 20 ) , and 1426 who were identified by the ASP method ( median = 1365 ) . CONCLUSION The ASP method of donor selection for refractory alloimmunized patients appears as effective as HLA matching or crossmatching . Far more donors are identified in a file of HLA-typed donors by the ASP method than by HLA matching , and this indicates that the ASP method provides important advantages regarding the availability of compatible platelet components BACKGROUND We conducted a multi-institutional , r and omized , blinded trial to determine whether the use of platelets from which leukocytes had been removed by a filter or that had been treated with ultraviolet B irradiation would prevent the formation of antiplatelet alloantibodies and refractoriness to platelet transfusions . METHODS Patients who were receiving induction chemotherapy for acute myeloid leukemia were r and omly assigned to receive one of four types of platelets transfusions : unmodified , pooled platelet concentrates from r and om donors ( control ) ; filtered , pooled platelet concentrates from r and om donors ( F-PC ) ; ultraviolet B-irradiated , pooled platelet concentrates from r and om donors ( UVB-PC ) ; or filtered platelets obtained by apheresis from single r and om donors ( F-AP ) . All patients received transfusions of filtered , leukocyte-reduced red cells . RESULTS Of 530 patients with no alloantibodies at base line , 13 percent of those in the control group produced lymphocytotoxic antibodies and their thrombocytopenia became refractory to platelet transfusions , as compared with 3 percent in the F-PC group , 5 percent in the UVB-PC group , and 4 percent in the F-AP group ( P < or = 0.03 for each treated group as compared with the controls ; there were no significant differences among the treated groups ) . Lymphocytotoxic antibodies were found in 45 percent of the controls , as compared with 17 to 21 percent in the treated groups ( P<0.001 for each treated group as compared with the controls ; there were no significant differences among the treated groups ) . Antibodies against platelet glycoproteins developed in 6 to 11 percent of the patients , with no significant differences among the four groups . CONCLUSIONS Reduction of leukocytes by filtration and ultraviolet B irradiation of platelets are equally effective in preventing alloantibody-mediated refractoriness to platelets during chemotherapy for acute myeloid leukemia . Platelets obtained by apheresis from single r and om donors provided no additional benefit as compared with pooled platelet concentrates from r and om donors In this prospect i ve study , 26 consecutive patients being treated for haematological malignancies receiving st and ard ( i.e. non-leucocyte-depleted ) blood components were observed for the development of refractoriness to platelet transfusions . One hundred and sixteen of the 266 ( 44 % ) platelet transfusions failed to produce a satisfactory response . In 102/116 ( 88 % ) , the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness . Non-immune factors were present alone in 78/116 ( 67 % ) , and in combination with immune factors in a further 24/116 ( 21 % ) . Immune factors ( HLA and platelet-specific antibodies ) were present during 29/116 ( 25 % ) of unsuccessful platelet transfusions . Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of non-immune factors . The non-immune factors associated with refractoriness were often multiple , most frequently a combination of fever , infection and antibiotic therapy . This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied . It also suggests that measures for the prevention of HLA alloimmunisation , such as leucocyte depletion , may have a limited impact in reducing the incidence of refractoriness to platelet transfusions A prospect i ve study was undertaken to assess the values of platelet aggregometry , lymphocytotoxicity , and mixed lymphocyte cultures in selecting compatible donors for patients refractory to r and om platelet transfusions . Donors were selected at r and om without regard to HLA types . Concurrent with each platelet transfusion , platelet aggregometry and lymphocytotoxicity were performed using patient serum and donor cells . The results were compared with HLA types , MLC , and increments in platelet counts . Forty-one transfusions were given to 21 patients ; 27 were from related and 14 from unrelated donors . Platelet aggregometry was used successfully in selecting compatible donors in 37 cases ( 90 % ) with three false negative and one false positive results . Lymphocytotoxicity was useful in 73 per cent of cases with eight false negative and three false positive results . The response to platelet transfusions correlated poorly with HLA matches or MLC reactions . These data suggest platelet aggregometry and lymphocytotoxicity are useful cross matching techniques in selection of compatible platelet donors Sera from 12 multitransfused patients who were refractory to r and om-donor platelets were tested for lymphocytotoxic and leukoagglutinating antibodies using panel cells from various volunteers whose HLA-A and -B antigens were known . All sera contained leukoagglutinins reactive with cells from at least one panel member , whereas only 33 % had lymphocytotoxic antibodies . Patients whose sera reacted frequently with panel cells using the microcapillary agglutination technic seldom responded to HLA-matched paltelets , whereas those whose sera reacted infrequently usually responded satisfactorily . It is concluded that non-HLA antibodies may play a significant role in determining the responses to platelet transfusions in multi-transfused patients BACKGROUND The purpose s of this study were to determine the overall incidence of platelet refractoriness and alloimmunization among multiply transfused children on a medical oncology and bone marrow transplant service and to evaluate the effect of routine white cell reduction in blood components on that incidence . STUDY DESIGN AND METHODS The platelet transfusion records of 128 consecutive children admitted to the hospital and requiring blood component support for the treatment of disease were evaluated retrospectively . Mean corrected count increments ( CCIs ) for each patient were calculated for all r and om-donor platelet transfusions given within 7 days of the routine weekly testings of the patient 's serum for lymphocytotoxic antibodies ( LCTAbs ) . Mean CCIs for HLA-matched platelet transfusions were calculated separately for the patients receiving them . RESULTS Thirty-one patients ( 24 % ) had or developed persistently positive LCTAbs ( patient 's serum reacted with > or = 3/10 panel lymphocytes ) ; 22 ( 71 % ) of these patients had a mean CCI < 7.5 to r and om-donor platelet transfusions . In contrast , of the 97 patients with negative or transiently positive LCTAbs , only 25 ( 26 % ) had a mean CCI < 7.5 . The overall incidence of platelet refractoriness ( CCI < 7.5 ) was 37 percent . Patients with acute myelogenous leukemia had a significantly ( p < 0.01 ) reduced incidence ( 17 % ) of low CCIs , with or without positive LCTAbs , as compared to patients with other malignant or nonmalignant disorders ( 41 % ) . No difference in the incidence of LCTAbs or low CCIs was seen in patients undergoing allogeneic or autologous bone marrow transplant or receiving drug therapy only . Among the 24 patients who received HLA-matched platelets , only those with positive LCTAbs showed a significant improvement in CCIs over that achieved with r and om-donor platelet transfusions . Routine white cell reduction in red cell and platelet components with third-generation white cell filters was performed prior to transfusion in 73 of the patients . There was no significant difference between the incidence of LCTAbs and /or low CCIs in this group and that in the 55 children receiving unfiltered transfusions . CONCLUSION Alloimmunization and platelet refractoriness occur in pediatric oncology and bone marrow transplant patients , but the incidence -- particularly in children with acute myelogenous leukemia -- appears to be low . The detection of LCTAbs predicts a poor response to r and om-donor platelet transfusion , but most such patients show improved CCIs with HLA-matched platelets . Routine use of white cell-reduction filters has thus far failed to eliminate alloimmunization in children requiring prolonged blood component support Frequent platelet support is an essential part of the management of patients with severe aplastic anaemia and platelet transfusions from r and om donors are usually given as initial therapy . To evaluate those parameters that might correlate with the development of refractoriness to platelets from r and om donors , we performed a retrospective multivariate analysis in 264 patients with severe aplastic anaemia who presented for allogeneic bone marrow transplantation . Two hundred and ten ( 79.5 % ) of these patients had received multiple platelet and red cell transfusions , and 71 ( 34 % ) were refractory to r and om donor platelets . The strongest factor correlating with refractoriness was the presence of lymphocytotoxic antibodies , followed by the number of platelet units previously transfused . However , the latter variable attained significance only when the number of platelet units transfused exceeded 40 . When given HLA‐compatible platelet transfusions , only five ( 7 % ) of the refractory patients did not show a reasonable post‐transfusion platelet increment . Measures which would delay or prevent platelet alloimmunization might include a policy of therapeutic rather than prophylactic platelet transfusions , and referring patients early in the course of their disease for marrow grafting if a suitable donor is available The use of histocompatability antigen (HLA)‐matched platelets has been advocated for the support of thrombocytopenic cancer patients . We r and omized 78 newly diagnosed cancer patients prospect ively ( before thrombocytopenia ) to receive either HLA‐matched or mismatched single‐donor platelet transfusions . Three hundred forty‐one platelet transfusions were given for 80 separate episodes of therapy induced thrombocytopenia in 33 patients . Forty‐five patients receiving intensive chemotherapy did not develop significant ( < 20,000 platelets/mm3 ) thrombocytopenia and did not receive a platelet transfusion . No marked difference was observed between the matched and mismatched groups in regard to number of total platelet transfusions per patient ( median , 3 vs. 5 , respectively ; P = 0.076 ) , number of platelet transfusions per episode ( median , 3.0 vs. 3.5 , respectively ; P = 0.28 ) , or days between transfusions ( median , 2 vs. 2 , respectively , P > 0.4 ) . Bleeding episodes , although rare , tended to be of increased severity in the mismatched group . Febrile patients receiving mismatched platelets tended to have a lower posttransfusion increment increase than their nonfebrile counterparts ( P = 0.068 ) , although a similar trend could not be demonstrated between febrile and nonfebrile patients who received matched platelets ( P = 0.22 ) . Patients treated as out patients had significantly higher posttransfusion increments than when transfused as in patients when they were given mismatched platelets ( P < 0.0005 ) . Development of antiplatelet antibody did not appear to affect response to platelet transfusions . Only one patient developed sustained high‐level antibody titers . In patients where thrombocytopenia was significant , the transfusion of HLA‐matched platelets did not appear to offer a significant advantage . However , HLA‐matched platelet transfusions tended to be associated with higher posttransfusion increments in febrile patients and a trend toward fewer severe bleeding episodes . A multi‐institution trial containing a large number of patients is needed to evaluate trends observed in this study Summary . Recent studies have shown that the incidence of alloimmunization due to repeated platelet transfusions from r and om donors may be reduced by the use of leucocyte‐poor blood components . These results were confirmed by this study , where 16 % of patients with acute leukaemia undergoing initial chemotherapy and receiving leucocyte‐poor blood components developed lymphocytotoxic antibodies , compared with 48 % of patients in a control group receiving st and ard ( non‐leucocyte‐depleted ) blood components . In a third group , who received leucocyte‐poor blood components and HLA‐matched platelets , none of the patients developed lymphocytotoxic antibodies . There was a low incidence of platelet‐specific antibodies ( 8 % ) but no difference between the three groups . Improved methods of removing leucocytes from blood components appear to offer the best approach for minimizing HLA alloimmunization , as the provision of HLA‐matched platelet donors for prophylactic platelet support of all patients is not feasible BACKGROUND HLAMatchmaker ( HLAMM ) is an algorithm that determines donor-recipient histocompatibility based on HLA type . This study determines the effectiveness of HLAMM in identifying suitable platelet ( PLT ) donors for refractory patients . STUDY DESIGN AND METHODS Data from a previous prospect ively r and omized multicenter study comparing cross-reactive group (CREG)-matched versus serologic crossmatch-selected PLT transfusions in refractory patients were analyzed . By use of HLAMM , the compatibility of donor-recipient pairings was determined as the number of donor triplet mismatches ( TMMs ) and eplet mismatches ( EMMs ) and compared against the posttransfusion PLT corrected count increment ( CCI ) . The data included 73 patients who received up to two CREG-matched and crossmatch-selected PLT transfusions each ( 214 transfusions analyzed ) . RESULTS TMM and EMM values correlated well with CREG match grade . A and BU matches had TMM and EMM values of 0 ; BX matches had TMMs and EMMs of 4 and 6 respectively ; and C and D matches had TMMs of 10 to 21 and EMMs of 13 to 24 . Fewer mismatches ( TMM or EMM ) predicted better transfusion outcomes ( p < 0.05 ) . The median 1-hour CCI was 8000 with TMMs of not more than 9 versus 6000 with TMMs of more than 9 . The median 1-hour CCI was 7954 with EMMs of not more than 11 versus 6356 with EMMs of more than 11 . The positive predictive value of the different methods in producing a 1-hour CCI of more than 7500 were comparable : TMM , 56 percent ; EMM , 54 percent ; CREG , 50 percent ; and crossmatching , 45 percent ( p > 0.05 ) . CONCLUSIONS HLAMM ( both TMM and EMM ) successfully identified donors associated with good transfusion outcomes in refractory recipients and represents an acceptable method of choosing donors for refractory patients BACKGROUND For HLA-alloimmunized patients , platelet ( PLT ) concentrations are provided either at matched HLA-A and HLA-B loci or by serologic cross-reactivity groups ( CREG ) matching strategy . However , this method has some limitations . STUDY DESIGN AND METHODS In this study , the epitope-based matching ( EBM ) method was evaluated for selecting proper HLA-typed PLTs for patients with PLT transfusion refractoriness . Bead-based single-antigen HLA antibody detection method and HLAMatchmaker software were used to define the epitopes recognized by HLA-specific antibodies and to select compatible PLTs for nine patients with alloimmunized refractoriness . Corrected count increments ( CCIs ) were prospect ively determined to compare successful transfusion rates among different matching methods in 142 PLT transfusions . In addition , HLA antibodies were serially detected to see whether any emerging antibodies appeared after receiving the EBM-matched PLTs . RESULTS The transfusion success rates evaluated with 1-hour CCIs for perfect matching or lacking any mismatching at HLA-A and -B locus (A/BU)-matched , CREG-matched , and EBM-matched PLTs were 85.2 , 63.2 , and 83.7 % , respectively . Compared to CREG-matched PLTs , EBM-matched PLTs showed better transfusion results ( p = 0.035 ) . In the follow-up study ( 7 months ; range , 3 - 13 months ) , no emerging HLA-specific antibodies were detected after receiving EBM-matched PLTs . CONCLUSIONS EBM performed on the basis of bead-based single-antigen HLA antibody detection coupled with the HLAMatchmaker program is recommended in choosing proper PLTs for refractory patients when A/BU-matched PLTs were not available |
544 | 23,805,818 | CONCLUSIONS Review ed r and omized controlled trials showed varied success of MI in improving oral health . | BACKGROUND The control and management of many oral health conditions highly depend on one 's daily self-care practice and compliance to preventive and curative measures .
Conventional ( health ) education ( CE ) , focusing on disseminating information and giving normative advice , is insufficient to achieve sustained behavioral changes .
A counseling approach , motivational interviewing ( MI ) , is potentially useful in changing oral health behaviors .
This systematic review aims to synthesize the evidence on the effectiveness of MI compared with CE in improving oral health . | One hundred twenty-three male veterans were r and omly assigned to control , education , and psychological groups to improve oral hygiene behavior . The educational group received four 40-min sessions design ed to increase knowledge of the causes and prevention of dental disease . The psychological intervention also consisted of four 40-min sessions . However , a psychologist provided the intervention using a Stage of Change intervention . The control group received pre- and post-testing only . There were no significant changes in dental knowledge for the control group while the increases in dental knowledge in the educational and psychological groups were similar and statistically significant . Pre-Post change scores for flossing self-efficacy scores showed significant changes for all groups . The magnitude of changes was similar when the control and educational groups were compared . In contrast , the psychological intervention group demonstrated significantly greater flossing self-efficacy changes when compared to either the control or the educational groups . These results suggest that increases in self-efficacy may be an important component of interventions design ed to change health behavior and may serve a role in evaluating and comparing the efficacy of these interventions PURPOSE The proximate use of illicit drugs or alcohol ( substance use ) is the most common precipitator of facial injuries among socioeconomically disadvantaged population s. Reducing these risky behaviors could minimize adverse health sequelae and potential reinjury . The objective of our study was to test whether a culturally competent , personalized motivational intervention incorporated into surgical care could significantly reduce existing substance use behaviors in facial injury patients . PATIENTS AND METHODS Substance-using subjects ( n = 218 ) presenting with facial injuries to a level 1 trauma center were r and omly assigned to either a personalized motivational intervention ( PMI ) condition or a health-information ( HI ) control condition . After a brief assessment of the individual 's substance use severity and willingness to change these behaviors , both groups attended 2 counseling sessions with a trained interventionist . The PMI subjects ( n = 118 ) received individualized , motivational interventions , whereas the HI subjects ( n = 100 ) received only general health information . Both groups were reassessed at 6 and 12 months postinjury , and changes in substance-use patterns were measured to assess the effects of intervention . RESULTS The PMI and HI groups were closely matched on their sociodemographic and substance use characteristics . Subjects in the PMI group showed statistically significant declines in drug use at both the 6- and 12-month assessment s. The intervention 's effect on lowering illicit drug use was greatest at the 6-month assessment but had weakened by the 1-year follow-up . The efficacy of the PMI was moderated by an individual 's initial drug use severity ; individuals with greater drug use dependency at baseline were seen to have larger intervention effects , as did individuals who were most aware of their drug problem and willing to change their substance use behaviors . Unlike illicit drug use , changes in alcohol use did not differ significantly between the intervention and control groups , irrespective of an individuals ' recognition of the alcohol problem or willingness to take steps to address it . CONCLUSION A culturally competent , motivational intervention integrated into the care of vulnerable patients with facial injury can reduce illicit drug use behaviors . Subgroups of injured patients appear to benefit most from such personalized motivational interventions . A better articulation of target population s , intervention content , and delivery would allow for directed interventions and an appropriate focusing of limited time and health care re sources We describe a r and omized trial design ed to evaluate the effectiveness of a smokeless tobacco cessation intervention delivered by dental hygienists as part of a patient 's regularly scheduled cleaning visit . Seventy-five practice s were r and omized to continue their usual care ( n=25 ; 239 smokeless tobacco using patients enrolled ) or to receive training to provide a tobacco cessation intervention ( n=50 ; 394 smokeless tobacco using patients enrolled ) . Patient reports indicated that the training program was successful in getting hygienists to implement the intervention . The intervention produced a strong effect on sustained quitting for smokeless tobacco users but had no impact on secondary outcomes , including unsuccessful quit attempts , future intent to quit using smokeless tobacco , and change in readiness to quit using . Frequency of smokeless tobacco use and receipt of specific components of the intervention , including the video and written material s , predicted sustained cessation . Since this intervention was delivered by dental hygienists as part of a patient 's regularly scheduled cleaning visit , it is easily disseminable OBJECTIVES This pragmatic r and omized trial evaluated the effectiveness of a tailored educational intervention on oral health behaviors and new untreated carious lesions in low-income African-American children in Detroit , Michigan . METHODS Participating families were recruited in a longitudinal study of the determinants of dental caries in 1021 r and omly selected children ( 0 - 5 years ) and their caregivers . The families were examined at baseline in 2002 - 2004 ( Wave I ) , 2004 - 2005 ( Wave II ) and 2007 ( Wave III ) . Prior to Wave II , the families were r and omized into two educational groups . An interviewer trained in applying motivational interviewing principles ( MI ) review ed the dental examination findings with caregivers assigned to the intervention group ( MI + DVD ) and engaged the caregiver in a dialogue on the importance of and potential actions for improving the child 's oral health . The interviewer and caregiver watched a special 15-minute DVD developed specifically for this project based on data collected at Wave I and focused on how the caregivers can ' keep their children free from tooth decay ' . After the MI session , the caregivers developed their own preventive goals . Some families in this group chose not to develop goals and were offered the project-developed goals . The goals , if defined , were printed on glossy paper that included the child 's photograph . Families in the second group ( DVD-only ) were met by an interviewer , shown the DVD , and provided with the project 's recommended goals . Both groups of families received a copy of the DVD . Families in the MI + DVD group received booster calls within 6 months of the intervention . Both caregivers and the children were interviewed and examined after approximately 2 years ( Wave III : 2007 ) . RESULTS After 6-month of follow-up , caregivers receiving MI + DVD were more likely to report checking the child for ' precavities ' and making sure the child brushes at bedtime . Evaluation of the final outcomes approximately 2 years later found that caregivers receiving the MI + DVD were still more likely to report making sure the child brushed at bedtime , yet were no more likely to make sure the child brushed twice per day . Despite differences in one of the reported behaviors , children whose caregivers received the motivational intervention did not have fewer new untreated lesions at the final evaluation . CONCLUSIONS This study found that a single motivational interviewing intervention may change some reported oral health behaviors , it failed to reduce the number of new untreated carious lesions This cluster-r and omized pragmatic ( effectiveness ) trial tested maternal counseling based on Motivational Interviewing ( MI ) as an approach to control caries in indigenous children . Nine Cree communities in Quebec , Canada were r and omly allocated to test or control . MI-style counseling was delivered in test communities to mothers during pregnancy and at well-baby visits . Data on outcomes were collected when children were 30 months old . Two hundred seventy-two mothers were recruited from the 5 test and 4 control communities . Baseline characteristics were comparable but not equivalent for both groups . At trial ’s end , 241 children had follow-up . The primary analysis outcome was enamel caries with substance loss ( d2 ) ; no statistically significant treatment effect was detected . Prevalence of treated and untreated caries at the d2 level was 76 % in controls vs. 65 % in test ( p = 0.17 ) . Exploratory analyses suggested a substantial preventive effect for untreated decay at or beyond the level of the dentin , d3 ( prevalences : 60 % controls vs. 35 % test ) , and a particularly large treatment effect when mothers had 4 or more MI-style sessions . Overall , these results provide preliminary evidence that , for these young , indigenous children , an MI-style intervention has an impact on severity of caries ( clinical trial registration IS RCT N41467632 ) OBJECTIVES Primary care medical clinics are good setting s for smoking interventions . This study extends this strategy with a smokeless tobacco intervention delivered by dentists and dental hygienists in the course of routine dental care . METHODS Male users of moist snuff and chewing tobacco ( n = 518 ) were identified by question naire in clinic waiting rooms and then r and omly assigned to either usual care or intervention . The intervention included a routine oral examination with special attention to the part of the mouth in which tobacco was kept and an explanation of the health risks of using smokeless tobacco . After receiving unequivocal advice to stop using tobacco , each patient viewed a 9-minute videotape , received a self-help manual , and was briefly counseled by the dental hygienist . RESULTS Long-term success was defined as no smokeless tobacco use at both 3- and 12-month follow-ups , with those lost to follow-up counted as smokeless tobacco users . The intervention increased the proportion of patients who quit by about one half ( 12.5 % vs 18.4 % , P < .05 ) . CONCLUSIONS These results demonstrate the efficacy of a brief dental office intervention for the general population of smokeless tobacco users AIM To develop and test the methodology of an intervention to reduce avoidance of dental care among adolescents , and to measure the respondents ' beliefs regarding the intervention ( credibility and cognitions ) . METHODS Based on a group comparison design a sample of 18 year olds ( n=50 ) with dental non-attendance behaviour was r and omly selected to three experimental and one control group . Subjects were surveyed with one baseline question naire and one post-intervention question naire , to evaluate their beliefs regarding the program . Two different instruments were tested : 1 ) cards representing different statements related to previous dental experiences , possible reasons for attending ( pros ) and not attending ( cons ) dental appointments , and preferences for future treatment . Cards were selected based on individual priority ; 2 ) a brief , structured telephone interview based on Motivational Interviewing . The instruments were tested separately ( groups I and II ) and in combination ( group III ) . Subjects in the control group ( group IV ) were given conventional health education . RESULTS Subjects in the experimental groups had significantly higher credibility scores to the statement " How much easier do you perceive dental treatment to be for you , based on this program " , compared with the control group ( p<0.05 ) . They had also more positive beliefs to the statement " I think the interviewer liked to talk to me " ( p<0.05 ) than controls . CONCLUSION A question naire sent to non-attending adolescents followed by a brief telephone call based on Motivational Interviewing appears to be a credible intervention for adolescents avoiding dental care AIM Because patient adherence to oral hygiene is essential for periodontal treatment success , the aim of the study was to assess whether a motivational interview addressing the five dimensions of Leventhal 's theory performed better than conventional basic instruction on improving compliance with plaque control among patients with periodontitis . MATERIAL S AND METHODS A r and omized controlled clinical trial design was used in which a group of patients underwent a motivational interview in addition to classical consultation . A control group received only the st and ard consultation . The O'Leary Plaque Index was used to judge the oral hygiene at baseline and at 1 month follow-up . Patient satisfaction with the dental visit was scored using a specific question naire . RESULTS At baseline , the mean full mouth plaque score varied between 55 % ( experimental group ) and 58 % ( control group ) . Patients in the experimental group had a higher oral hygiene improvement ( 21 ± 20 % versus 4 ± 5 % , p < 0.001 ) 1 month post-treatment . The motivational interview result ed in greater satisfaction scores compared with those of patients in the control group : 10.55 ± 1.53 versus 8.82 ± 2.40 , p = 0.014 . CONCLUSIONS This new concept of motivational interview is a promising approach and can be useful for counselling-related periodontal disorders AIM To evaluate the effectiveness of an individually tailored oral health educational programme for oral hygiene self-care in patients with chronic periodontitis compared with the st and ard treatment . MATERIAL AND METHOD A r and omized , evaluator-blinded , controlled trial with two different active treatments were used with 113 subjects ( 60 females and 53 males ) r and omly allocated to an experimental or a control group . The individually tailored oral health educational programme was based on cognitive behavioural principles and the individual tailoring for each participant was based on participants ' thoughts , intermediate , and long-term goals , and oral health status . The effect of the programmes on gingivitis [ gingival index ( GI ) ] , oral hygiene [ plaque indices ( PlI ) and self-report ] , and participants ' global rating of treatment was evaluated 3 and 12 months after oral health education and non-surgical treatment . RESULTS Between baseline and the 12-month follow-up , the experimental group improved both GI and PlI more than the control group . The mean gain-score difference was 0.27 for global GI [ 99.2 % confidence interval ( CI ) : 0.16 - 0.39 , p<0.001 ] and 0.40 for proximal GI ( 99.2 % CI : 0.27 - 0.53 , p<0.001 ) . The mean gain-score difference was 0.16 for global PlI ( 99.2 % CI : 0.03 - 0.30 , p=0.001 ) , and 0.26 for proximal PlI ( 99.2 % CI : 0.10 - 0.43 , p<0.001 ) . The subjects in the experimental group reported a higher frequency of daily inter-dental cleaning and were more certain that they could maintain the attained level of behaviour change . CONCLUSION The individually tailored oral health educational programme was efficacious in improving long-term adherence to oral hygiene in periodontal treatment . The largest difference was for interproximal surfaces AIMS To assess the impact of two methods of brief nurse-delivered brief interventions in reducing drinking variables in hazardous drinkers with alcohol-related facial injuries . METHODS A r and omised controlled trial of two brief interventions involving hazardous drinkers with facial trauma in three Oral and Maxillofacial Surgery outpatient clinics in the West of Scotl and ; 194 patients were recruited and r and omised to have either a nurse-led brief motivational intervention ( intervention group ) or a leaflet about alcohol misuse ( control group ) . Patients were followed up at 3 and 12 months after the intervention and drinking variables reassessed . RESULTS A brief motivational intervention for alcohol provided by a nurse was more effective than a leaflet in helping some patients with facial trauma to reduce their alcohol consumption 12 months after the intervention ( p<0.05 ) . CONCLUSIONS Facial trauma in the West of Scotl and is strongly associated with alcohol misuse and is a recurrent disease , particularly among those who drink heavily . A nurse-delivered brief motivational intervention is effective in helping patients with high scores in the Alcohol Use Disorders Identification Test to reduce their drinking , and this effect was apparent 12 months after the intervention PURPOSE The purpose s of this r and omized controlled trial were to : ( 1 ) test motivational interviewing ( MI ) to prevent early childhood caries ; and ( 2 ) use Poisson regression for data analysis . METHODS A total of 240 South Asian children 6 to 18 months old were enrolled and r and omly assigned to either the MI or control condition . Children had a dental exam , and their mothers completed pretested instruments at baseline and 1 and 2 years postintervention . Other covariates that might explain outcomes over and above treatment differences were modeled using Poisson regression . Hazard ratios were produced . RESULTS Analyses included all participants whenever possible . Poisson regression supported a protective effect of MI ( hazard ratio [HR]=0.54 (95%CI=035 - 0.84)-that is , the M/ group had about a 46 % lower rate of dmfs at 2 years than did control children . Similar treatment effect estimates were obtained from models that included , as alternative outcomes , ds , dms , and dmfs , including " white spot lesions . " Exploratory analyses revealed that rates of dmfs were higher in children whose mothers had : ( 1 ) prechewed their food ; ( 2 ) been raised in a rural environment ; and ( 3 ) a higher family income ( P<.05 ) . CONCLUSIONS A motivational interviewing-style intervention shows promise to promote preventive behaviors in mothers of young children at high risk for caries BACKGROUND The purpose of this study was to compare the effect of a motivational interviewing ( MI ) counseling visit with traditional health education for mothers of young children at high risk of developing dental caries . METHODS The authors enrolled 240 infants aged 6 to 18 months and their mothers in the study and r and omly assigned them to MI or traditional health education ( control ) groups . Mothers in the control group received a pamphlet and watched a videotape . Those in the MI group received the pamphlet and watched the videotape , as well as received an MI counseling session and six follow-up telephone calls during the first year . There were no interventions in year 2 . RESULTS After two years , children in the MI group exhibited significantly less new caries ( decayed or filled surfaces ) than those in the control group ( that is , a protective effect of MI ) ( odds ratio = 0.35 , 95 percent confidence interval = 0.15 to 0.83 ) . CONCLUSIONS MI is a promising approach that warrants further attention in a variety of dental context s. CLINICAL IMPLICATION S The results of this study show that MI has a protective effect with regard to the development of early childhood caries . One reason for this clinical effect is greater compliance with recommended fluoride varnish treatment regimens in families who received MI counseling compared with families who received traditional education More knowledge is needed regarding what works to prevent oral health problems and reduce disparities in oral health . Motivational interviewing ( MI ) has demonstrated utility for improving health behavior , including among those with severe mental illness . This study tests whether MI enhances the efficacy of an oral health education intervention in individuals with severe mental illness . Sixty individuals were r and omly assigned to MI plus oral health education or oral health education alone . Plaque scores , oral health knowledge , and self-regulation were assessed at baseline and at 4 and 8 weeks . Repeated- measures ANOVA showed improvement ( p < 0.05 ) in plaque , autonomous regulation , and oral health knowledge across time for both groups ; however , individuals receiving MI improved significantly more when compared with those receiving oral health education alone . Results suggest that MI is effective for enhancing short-term oral health behavior change for people with severe mental illness and may be useful for the general population AIM To evaluate an individually tailored oral health educational programme ( ITOHEP ) on periodontal health compared with a st and ard oral health educational programme . A further aim was to evaluate whether both interventions had a clinical ly significant effect on non-surgical periodontal treatment at 12-month follow-up . MATERIAL AND METHOD A r and omized , evaluator-blinded , controlled trial with 113 subjects ( 60 females and 53 males ) r and omly allocated into two different active treatments was used . ITOHEP was based on cognitive behavioural principles and motivational interviewing . The control condition was st and ard oral hygiene education ( ST ) . The effect on bleeding on probing ( BoP ) , periodontal pocket depth , " pocket closure " i.e. percentage of periodontal pocket > 4 mm before treatment that were < 5 mm after treatment , oral hygiene [ plaque indices ( PlI ) ] , and participants ' global rating of oral health was evaluated . Preset criteria for PlI , BoP , and " pocket closure " were used to describe clinical ly significant non-surgical periodontal treatment success . RESULTS The ITOHEP group had lower BoP scores 12-month post-treatment ( 95 % confidence interval : 5 - 15 , p<0.001 ) than the ST group . No difference between the two groups was observed for " pocket closure " and reduction of periodontal pocket depth . More individuals in the ITOHEP group reached a level of treatment success . Lower PlI scores at baseline and ITOHEP intervention gave higher odds of treatment success . CONCLUSIONS ITOHEP intervention in combination with scaling is preferable to the ST programme in non-surgical periodontal treatment 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 OBJECTIVES We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation , reduction in tobacco use , number of quit attempts , and change in readiness to quit . METHODS We r and omized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states ( Mississippi , New York , and Oregon ) to the intervention ( brief advice and assistance , including nicotine replacement therapy ) or usual care group . RESULTS We enrolled 2549 smokers . Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up , for both point prevalence ( F(1,12 ) = 6.84 ; P < .05 ) and prolonged abstinence ( F(1,12 ) = 14.62 ; P < .01 ) than did those in the usual care group . CONCLUSIONS The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers . Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans PURPOSE The objective of the present study was to study the ability to influence young at-risk patients ' attitudes toward tobacco use through two intervention methods that were performed by dental health professionals . MATERIAL S AND METHODS Two interventions , a brief individual motivational interview and an adapted school lecture , were studied , and both were compared with a control group . Before and after interventions , a question naire was used . Patients born in 1989 and 1992 who were judged by the dental personnel as potentially at risk for dental diseases , a total of 301 individuals , were included . RESULTS Both before and after interventions , the results showed a generally negative attitude towards tobacco use . A majority of the participants were positive towards measures that were taken to control the spread of tobacco use , younger participants ( born 1992 ) to a greater extent ( 73 % ) than the older participants ( born 1989 ) ( 54 % ) . Important factors that kept the participants away from tobacco use were the harmful effects and the approaches of parents and friends . The older participants believed to a greater extent that they would try smoking as adults . No change in tobacco use was registered after intervention , although the participants reported an increased use among friends . CONCLUSIONS The two pedagogical methods that were used in the present study influenced the young people 's attitudes towards tobacco use only to a small extent . However , the period between 12 and 15 years old seems to provide a good opportunity to influence attitudes towards tobacco . The adolescents ' dem and for interactive learning and their development of attitudes and tobacco use habits in relation to family and friends provide opportunities to use new pedagogical models AIM The aim of this study was to compare the effectiveness of oral health counseling sessions with traditional oral hygiene education in orthodontic patients with fixed appliances . MATERIAL S AND METHODS STUDY DESIGN r and omised control trial with experimental and control group . A group of 99 adolescents with fixed orthodontic appliances were r and omly assigned to oral health counseling ( experimental ) or traditional health education ( control ) group . Subjects in the control group received verbal instructions and a demonstration of the modified Bass brushing technique on a model . The experimental group also received the verbal information with demonstration on the model and in addition a personalised 40-minutes counseling session on oral hygiene . Plaque Index ( PI ) and gingivitis ( G ) were recorded before , 1 and 6 months after the counseling session/traditional education . RESULTS Oral health counseling and traditional education improved the oral hygiene of orthodontic patients . PI values were significantly lower after 6 months compared to the baseline in both groups , but the prevalence of gingival inflammation remained significantly lower only in the experimental group . CONCLUSION Oral health counseling increased plaque removal efficacy and control of gingival inflammation . The efficiency of counseling and traditional education was similar . Counseling is a promising approach that warrants further attention in a variety of dental context OBJECTIVES Patient engagement in effective oral hygiene following periodontal therapy is essential to long-term success . Motivational interviewing ( MI ) is a behavioural counselling approach documented to positively influence behaviour change related to smoking , diabetes control and medication adherence . Emerging evidence suggests utility of MI to improve oral health . The objective of this study was to evaluate whether the use of brief motivational interviewing ( BMI ) is effective in improving internal motivation for oral hygiene behaviour . METHODS A convenience sample of fifty-six previously treated periodontal patients who were in maintenance yet presented with signs of clinical inflammation were recruited to participate in this single blind , r and omized controlled trial . Patients were r and omly assigned to receive either BMI in conjunction with traditional oral health education ( TOHE ) , ( n = 29 ) or TOHE alone ( n = 27 ) . Bleeding on probing scores ( BOP ) , plaque index ( PI ) , pocket depths ( PD ) , motivation ( M ) , autonomous regulation ( AR ) controlled regulation ( CR ) and oral health knowledge ( K ) were assessed at baseline , 6 weeks and 12 weeks . RESULTS Statistically significant decreases were found over time for BOP ( P = 0.001 ) , PI ( P = 0.001 ) and PD 4 - 6 mm ( P = 0.001 ) for both groups . Differences in clinical parameters between groups were not evident at either 6 or 12 weeks . CONCLUSION Results show that a one-time MI session is insufficient for improving oral hygiene in long-st and ing maintenance patients AIM The aim of this cost-effectiveness analysis ( CEA ) , performed from a societal perspective , was to compare costs and consequences of an individually tailored oral health educational programme ( ITOHEP ) based on cognitive behavioural strategies integrated in non-surgical periodontal treatment compared with a st and ard treatment programme ( ST ) . MATERIAL AND METHODS A r and omized ( n = 113 ) , evaluator-blinded , controlled trial , with two different active treatments , was analysed with respect to their costs and consequences 12 months after non-surgical treatment . Costs referred to both treatment costs and costs contributed by the patient . Consequences ( outcome ) were expressed as the proportion of individuals classified as having reached the pre-set criteria for treatment success after non-surgical treatment ( " successful-NSPT " ) . RESULTS More individuals in the ITOHEP group reached the pre-set criteria for treatment success than individuals in the ST group did . The CEA revealed an incremental cost-effectiveness of SEK1724 [ € 191.09 ; SEK9.02 = € 1 ( January 2007 ) ] per " successful-NSPT " case , of which treatment costs represented SEK1189 ( € 131.82 ) , using the unit cost for a dental hygienist . CONCLUSION The incremental costs per " successful-NSPT " case can be considered as low and strengthens the suggestion that an ITOHEP integrated into non-surgical periodontal treatment is preferable to a st and ardized education programme AIM To evaluate the effect of a single session of motivational interviewing ( MI ) on self-performed periodontal infection control . MATERIAL AND METHODS A r and omized , examiner masked , controlled clinical trial of 6-month duration was performed involving 44 patients with chronic periodontitis , referred for periodontal treatment . At baseline , all subjects were examined concerning marginal gingival bleeding ( MBI ) and plaque ( PI ) . Test subjects received a single MI-session before initiation of the periodontal treatment . Otherwise , all patients followed the same treatment protocol for conventional educational intervention and non-surgical periodontal therapy . Efficacy variables for evaluation of self-performed periodontal infection control were MBI ( primary variable ) and PI . RESULTS The MI intervention result ed in a negligible decrease ( 3 - 4 % ) in MBI and PI that was not significantly different from the changes observed in the control group without any intervention . Neither was any additive effect of the initial MI-session found on the st and ard of oral hygiene subsequent to conventional treatment . A desirable MBI score of ≤20 % at the end of treatment was associated with being a female patient , whereas high plaque scores at baseline counteracted a corresponding desirable final PI of ≤20 % . CONCLUSION A single freest and ing MI session as a prelude to conventional periodontal treatment had no significant effect on the individuals ' st and ard of self-performed periodontal infection control in a short-term perspective |
545 | 29,334,694 | Whilst housing did not affect body weight , both food intake and visceral adipose tissue mass were significantly higher in individually compared with socially housed animals .
A combination of emotional stress and lack of social thermoregulation likely contributed to these effects . | Rats and mice are widely used to study environmental effects on psychological and metabolic health .
Study design s differ widely and are often characterized by varying ( social ) housing conditions .
In itself , housing has a profound influence on physiology and behaviour of rodents , affecting energy balance and sustainable metabolic health .
However , evidence for potential long-term consequences of individual versus social housing on body weight and metabolic phenotype is inconsistent . | Background Cold-stimulated adaptive thermogenesis in brown adipose tissue ( BAT ) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity . We have recently shown high prevalence of BAT in adult humans , which was inversely related to body mass index ( BMI ) and body fat percentage ( BF% ) , suggesting that obesity is associated with lower BAT activity . Here , we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis ( CIT ) after applying a personalized cooling protocol . We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure . Methods and Findings After applying a personalized cooling protocol for maximal non-shivering conditions , BAT activity was determined using positron-emission tomography and computed tomography ( PET-CT ) . Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects . Combined with results from lean to morbidly obese subjects ( n = 39 ) from previous study , the collective data show a highly significant correlation between BAT activity and body composition ( P<0.001 ) , respectively explaining 64 % and 60 % of the variance in BMI ( r = 0.8 ; P<0.001 ) and BF% ( r = 0.75 ; P<0.001 ) . Obese individuals demonstrate a blunted CIT combined with low BAT activity . Only in BAT-positive subjects ( n = 26 ) mean energy expenditure was increased significantly upon cold exposure ( 51.5±6.7 J/s versus 44.0±5.1 J/s , P = 0.001 ) , and the increase was significantly higher compared to BAT-negative subjects ( + 15.5±8.9 % versus + 3.6±8.9 % , P = 0.001 ) , indicating a role for BAT in CIT in humans . Conclusions This study shows that in an extremely large range of body compositions , BAT activity is highly correlated with BMI and BF% . BAT-positive subjects showed higher CIT , indicating that BAT is also in humans involved in adaptive thermogenesis . Increasing BAT activity could be a therapeutic target in ( morbid ) obesity The cage systems commonly used for housing laboratory rats often result in sedentary and overweight animals , as a consequence of restricted opportunities for physical activity combined with ad libitum feeding . This can have implication s both for animal well-being and for the experimental outcome . Physical activity has several known positive effects on health and lifespan , and physical fitness might therefore be incorporated into the animal welfare concept . The aim of this study was to investigate if and how pen housing affects the physical activity and fitness of rats . Thirty-two juvenile male Sprague-Dawley rats were r and omly assigned to two different housing systems for a 4-week period . Sixteen rats were kept individually in st and ard Makrolon type III cages ( 42 × 26 × 18 cm ) furnished with black plastic tubes ( singly-housed , SI ) . The remaining rats were kept in groups of eight , housed in large floor pens ( 150 × 210 cm ) , which were furnished with various objects to increase environmental complexity ( pen-housed , PH ) . The body weight gain , and food and water intake of the rats were measured . During weeks 3 or 4 , home cage behaviour , urinary cortiosterone/creatinine ratios ( CO/CR ) , and muscle strength on an inclined plane , were measured . Enzyme activities and glycogen content were measured in tissue sample s from m. triceps brachii taken after euthanization at the end of the study . There were no significant differences between groups for food and water intake , but PH rats weighed 14 % less than SI rats after 4 weeks , and PH rats also had a more diverse behavioural pattern than SI rats . PH rats had significantly higher oxidative capacity ( 28 % more citrate synthase ( CS ) ) and greater glycogen content ( 28 % ) in their muscle sample s than SI rats . The PH rats performed significantly better on the inclined plane , both in the muscle strength test ( mean angle 75 ± 0.5 ° for PH rats and 69 ± 0.4 ° for SI rats ) and the endurance strength test ( mean time 233 ± 22 s for PH rats and 73 ± 14 s for SI rats ) . There was a negative correlation between body weight and results on the inclined plane for the PH rats . There were no significant differences between housing types with respect to CO/CR ratios . In conclusion , the large pen represents an environment that stimulates physical activity and more varied behaviour , which should be beneficial for the welfare of the animal Currently , environmental enrichment is a very common means of improving animal well-being , especially for laboratory animals . Although environmental enrichment seems to be a possible way for improving the well-being of animals , the consideration of housing laboratory animals should not only focus solely on animal well-being , manpower and economics but also on the precision and accuracy of the experimental results . The purpose of the present study was to evaluate the effects of enriched cages ( nest box , nesting material , climbing bar ) on body weight , haematological data and final organ weights . BALB/c , C57BL/6 and A/J mice , originated from Harlan Winkelmann , were used for the experiments - 16 animals of each strain . Animals at 3 weeks of age were marked and separated r and omly to enriched or non-enriched cages , in groups of four , half for each housing condition . Both cages were type III Makrolon cages , only the enriched cages contained a nest box , a wood bar for climbing and nesting material . Animals were kept in a clean animal room under specific pathogen free ( SPF ) conditions . Body weights were recorded every week . Blood sample s were collected at 14 weeks of age ( white blood cells ( WBC ) , red blood cells ( RBC ) , haemoglobin ( HGB ) , and haematocrit ( HCT ) were analysed ) . At 15 weeks of age , the animals were euthanized by CO2 in their home cages , and final body weight and organ weights ( heart , liver , kidney , adrenal , spleen and uterus ) were recorded immediately . Although nearly all the test variables were not affected by environmental enrichment in their mean values , the enriched group showed higher coefficients of variation in many variables , and strain differences of both housing conditions were not consistent . The influences of enrichment were shown to be strain- and test-dependent . Such effects may lead to an increase in the number of animals which is necessary or may change the experimental results , especially when a study , using enriched housing conditions , focuses on strain differences . Since the same enrichment design can result in different influences , a positive or a negative or no adverse effect , due to the strain and the variables studied , research ers need to collect more information before enrichment design s are introduced into experimental plans Ad libitum fed male Sprague-Dawley rats were r and omly assigned to be housed individually ( n=32 ) or four in each cage ( n=32 ) from five to 23 months of age . Body weight and body composition by bioimpedance analysis were monitored longitudinally . An equation for analysis of body composition was developed . Deaths and causes of death were recorded . Of the individually housed animals ( H1 ) 16 percent died , while 44 percent of those housed four in a cage ( H4 ) died , the most common causes of death being circulatory failure , nephritis and tumours of the hypophysis . Body weight increased in both groups over time , significantly more for H4 from 6months of age . Both fat free mass and total body fat increased in both groups over time . Fat in percent of body weight increased up to an age of 14months . H4 animals had significantly more fat from 11 to 20 months of age but lost weight , mostly fat when approaching 23months of age . The occiput-sacrum length of the animals increased up to 11months of age and stayed then constant . Animals in both groups grew also in the cross-sectional dimension . The H1 animals continued to grow all the time , while the growth of the H4 animals stopped at the age of 17 months , when the mortality started to become pronounced . It is concluded that housing conditions can modulate the outcome of the ageing of sedentary and otherwise not treated rats in long-term experiments . Further , the feasibility of monitoring body composition longitudinally with bioimpedance analysis was demonstrated The aim of the present study was to investigate the effects of glucocorticoids ( GCs ) on appetite and gene expression of the hypothalamic appetite regulatory peptides , neuropeptide Y ( NPY ) , agouti-related protein ( AGRP ) and cocaine and amphetamine-regulated transcript ( CART ) , in non-obese and obese rats . Both non-obese and obese rats were r and omly assigned to three groups : normal saline , low- and high-dose GC groups ( NSG , LDG and HDG , respectively ) , which received an intraperitoneal injection with normal saline ( 0.2 ml/100 g ) or hydrocortisone sodium succinate at 5 and 15 mg/kg , respectively , for 20 days . The expression levels of NPY , AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR . Non-obese and obese rats were found to undergo weight loss after GC injection , and a higher degree of weight loss was observed in the HDG rats . The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG ( p<0.05 ) . mRNA expression levels of the orexigenic neuropeptides , NPY and AGRP , and the anorexigenic neuropeptide , CART , were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats ( p<0.05 ) . GC treatment decreased appetite and body weight , induced apparent glucolipid metabolic disturbances and hyperinsulinemia , while down-regulated mRNA expression levels of the orexigenic neuropeptides , NPY and AGRP , and anorexigenic neuropeptide , CART , in the hypothalamus in the rats . The mechanism which induces this neuropeptide expression requires further study Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies |
546 | 26,940,430 | Changes were reported in several brain areas in FD patients including the frontal cortex , somatosensory cortex , insula , anterior cingulate cortex , thalamus , hippocampus , and amygdala .
These brain activity changes were associated with visceral hypersensitivity , dyspeptic symptoms , poorer quality of life , anxiety , and depression .
The results show that FD is associated with functional abnormalities in sensory and pain modulation , emotion , saliency , and homeostatic processing regions . | BACKGROUND There is increasing evidence in support of the presence of abnormal central changes ( compared to healthy controls ) in functional dyspepsia ( FD ) in addition to the peripheral changes in gastrointestinal tract .
PURPOSE This systematic review aims to provide an integrative underst and ing of the abnormal functional brain activity , visceral sensation , dyspeptic symptoms , and psychological changes of FD . | The experience of pain arises from both physiological and psychological factors , including one 's beliefs and expectations . Thus , placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations . However , controversy exists regarding whether placebos alter sensory pain transmission , pain affect , or simply produce compliance with the suggestions of investigators . In two functional magnetic resonance imaging ( fMRI ) experiments , we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions , including the thalamus , insula , and anterior cingulate cortex , and was associated with increased activity during anticipation of pain in the prefrontal cortex , providing evidence that placebos alter the experience of pain Abstract Although individual differences in fear and anxiety modulate the pain response and may even cause more suffering than the initiating physical stimulus , little is known about the neural systems mediating this relationship . The present study provided the first examination of the neural correlates of individual differences in the tendency to ( 1 ) feel anxious about the potentially negative implication s of physical sensations , as measured by the anxiety sensitivity index ( ASI ) , and ( 2 ) fear various types of physical pain , as indexed by the fear of pain question naire ( FPQ ) . In separate sessions , participants completed these question naires and experienced alternating blocks of noxious thermal stimulation ( 45–50 ° C ) and neutral thermal stimulation ( 38 ° C ) during the collection of whole‐brain fMRI data . Regression analyses demonstrated that during the experience of pain , ASI scores predicted activation of a medial prefrontal region associated with self‐focused attention , whereas FPQ scores predicted activation of a ventral lateral frontal region associated with response regulation and anterior and posterior cingulate regions associated with monitoring and evaluation of affective responses . These functional relationships can not be wholly explained by generalized anxiety ( indexed by STAI‐T scores ) , which did not significantly correlate with activation of any regions . The present findings may help clarify both the impact of individual differences in emotion on the neural correlates of pain , and the roles in anxiety , fear , and pain processing played by medial and orbitofrontal systems The endogenous opioid system is involved in stress responses , in the regulation of the experience of pain , and in the action of analgesic opiate drugs . We examined the function of the opioid system and μ-opioid receptors in the brains of healthy human subjects undergoing sustained pain . Sustained pain induced the regional release of endogenous opioids interacting with μ-opioid receptors in a number of cortical and subcortical brain regions . The activation of the μ-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience , with distinct neuroanatomical involvements . These data demonstrate the central role of the μ-opioid receptors and their endogenous lig and s in the regulation of sensory and affective components of the pain experience OBJECTIVE : The lack of a suitable disease-specific , health-related quality of life instrument for dyspepsia prompted the development of the Nepean Dyspepsia Index ( NDI ) . The utility of the NDI in functional dyspepsia is unknown . We aim ed to assess the validity of this new quality of life instrument for the first time in United States patients with documented functional dyspepsia . METHODS : The long form of the NDI contains a symptom index and 42 items design ed to measure impairment of subjects ’ ability to engage in and to enjoy relevant aspects of their life because of dyspepsia , as well as a ranking of the individual importance of each aspect . Patients ( n = 101 , mean age 51 yr , 62 % female ) who had a history of functional dyspepsia for ≥1 month and a negative endoscopy within the prior 1 yr were followed for 14 days . Patients completed the NDI and the vali date d Speilberger State-Trait Anxiety Inventory , Beck Depression Inventory , Short Form-36 , and a global assessment of symptoms and quality of life at baseline and 14 days later ; the NDI was also retested at 48 h and 2 wk . RESULTS : Five clinical ly relevant factors ( subscales ) , namely , tension/sleep , interference , eating/drinking , knowledge/control , and work/ study were identified by factor analysis , after incorporating individual importance ratings ( 25 items total ) . All subscales had excellent face validity and internal consistency ( Chronbach 's α , all > 0.85 ) . Reliability was also excellent ( intraclass correlations all > 0.84 ) . There were modest typically negative correlations between a number of the NDI subscales and the Short Form-36 , anxiety , and depression , indicating that the NDI is disease-specific and supporting its validity . Changes in NDI scales correlated moderately with global assessment of change ( total score r = −0.49 ) , indicating initial responsiveness . CONCLUSIONS : The Nepean Dyspepsia Index is a valid , disease-specific index for functional dyspepsia , measuring symptoms and health-related quality of life BACKGROUND & AIMS Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia ( FD ) . Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity . We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention . Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD . METHODS Brain (15)O-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions : no distention , sham distention , and isobaric distention to unpleasant or painful sensation . Pain , discomfort , nausea , and bloating during maximal distention were rated on visual analogue scales . Data were analyzed using statistical parametric mapping . RESULTS The threshold for painful distention was 6.6 + /- 3.8 mm Hg greater than the minimal distending pressure . At the corrected P level of less than .05 , subtraction analysis ( painful distention - no distention ) showed activations in bilateral gyrus pre central is , bilateral gyrus frontalis inferior , bilateral gyrus frontalis medialis , bilateral gyrus temporalis superior , bilateral cerebellar hemisphere , and left gyrus temporalis inferior . Sham distention minus no distention showed no activations . CONCLUSIONS Similar to healthy volunteers , proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri , putatively involved in regulation of hunger and satiety . In hypersensitive FD , these activations occur at significantly lower distention pressures . In contrast to findings in normosensitivity , none of the components of the medial pain system were significantly activated & NA ; Irritable bowel syndrome ( IBS ) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception . Previous studies in IBS have failed to demonstrate altered somatic or cutaneous perception . The aims of the study were to determine whether IBS patients have visceral hypersensitivity and cutaneous heat‐induced hyperalgesia restricted to lumbosacral dermatomes , consistent with a localized segmental mechanism . Twelve patients ( ten women , two men ) with IBS and 17 control subjects ( 13 women , four men ) rated pain intensity and unpleasantness to distension of the rectum ( 35 , 55 mmHg ) and thermal stimulation ( 45 , 47 ° C ) of the h and and foot . Patients with IBS demonstrated cutaneous allodynia/hyperalgesia to thermal pain applied to the h and and foot . The cutaneous hyperalgesia was pronounced in the lower extremity yet present in the upper extremity to a lesser extent . Psychological testing revealed the IBS patients report more state anxiety and a greater number of somatic symptoms that significantly correlated with most of the pain measures . However , they did not differ from controls on several personality trait measures . These results suggest that patients with IBS have visceral hyperalgesia and cutaneous hyperalgesia that is distributed over a considerable rostral‐caudal distance yet optimally expressed in lumbosacral dermatomes . This distribution is consistent with patterns of spinal hyperexcitability observed in experimentally induced persistent pain conditions OBJECTIVES : Acupuncture is a commonly used therapy for treating functional dyspepsia ( FD ) , although the mechanism remains unclear . The objectives of this study were to investigate the differences in cerebral glycometabolism changes evoked by acupuncture and sham acupuncture and to explore the possible correlations between brain responses and clinical efficacy . METHODS : In all , 72 FD patients were r and omly assigned to receive either acupuncture or sham acupuncture treatment for 4 weeks . Ten patients in each group were r and omly selected for fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography scans to detect cerebral glycometabolism changes . The Nepean Dyspepsia Index ( NDI ) and Symptom Index of Dyspepsia ( SID ) were used to evaluate the therapeutic effect . RESULTS : ( i ) The clinical data showed that after treatment the decrease in SID score in the acupuncture group was significantly greater than that in the sham acupuncture group ( P<0.05 ) . The increase in NDI score between the two groups did not differ ( P>0.05 ) , and only the improvement in NDI score in the acupuncture group was clinical ly significant . ( ii ) The neuroimaging data indicated that after treatment the acupuncture group showed extensive deactivation in cerebral activities compared with the sham acupuncture group . In the acupuncture group , the deactivations of the brainstem , anterior cingulate cortex ( ACC ) , insula , thalamus , and hypothalamus were nearly all related to the decrease in SID score and the increase in NDI score ( P<0.05 , corrected ) . In the sham acupuncture group , the deactivations of the brainstem and thalamus tended to be associated with the increase in NDI score ( P<0.1 , corrected ) . CONCLUSIONS : Acupuncture and sham acupuncture have relatively different clinical efficacy and brain responses . Acupuncture treatment more significantly improves the symptoms and quality of life of FD patients . The more remarkable modulation on the homeostatic afferent network , including the insula , ACC , and hypothalamus , might be the specific mechanism of acupuncture It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems . The rostral anterior cingulate cortex ( rACC ) and the brainstem are implicated in opioid analgesia , suggesting a similar role for these structures in placebo analgesia . Using positron emission tomography , we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC . We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia , but not during the pain-only condition . These findings indicate a related neural mechanism in placebo and opioid analgesia & NA ; Visceral pain/discomfort is the cardinal complaints and treatment targets for functional gastrointestinal disorders ( FGID ) . However , effective treatment for such pain is limited and often associated with high placebo effects . The mechanisms of placebo effects in visceral pain are unclear . We used functional neuroimaging to study the central representations of the placebo effect and its anticipation during esophageal pain in healthy adults . Fourteen subjects were enrolled . Pain extent , psychophysical inventories [ Pain Catastrophizing Scale ( PAS ) , visual analogue scale ( VAS ) and short‐form McGill question naire ] , and brain activity upon placebo intervention and upon anticipation were assessed in response to esophageal balloon distension . Large reductions of pain extent , VAS rating , short‐form McGill question naire scores , and brain activity in the visceral pain matrix [ thalamus , somatosensory cortices , insula , prefrontal cortex ( PFC ) , anterior cingulate cortex ] were observed upon placebo treatment . The aforementioned brain areas and the bilateral amygdala were significantly correlated with decreased pain extent and VAS in response to placebo . The ventral lateral PFC ( VLPFC ) was associated with increased activity during anticipation of visceral pain . PAS can not predict the placebo effect in visceral pain . In conclusion , pronounced placebo analgesia was coupled with prominent changes of brain activity in visceral pain matrix , which are thus likely involved in high placebo efficacy during the treatment of visceral pain in FGID . VLPFC activation during the anticipation of placebo analgesia suggests top‐down control in the modulation of pain experience |
547 | 23,269,446 | Based on our results , we conclude that there is evidence in favour of the extravesical ureteroneocystostomy for having a smaller amount of urological complications in kidney transplantation | Urological complications are still a major problem postoperatively with a reported incidence of up to 30 % , associated with significant morbidity , mortality , prolonged hospital stay and high medical costs .
To date , there is no evidence favouring either an extravesical or an intravesical approach .
The purpose of this systematic review and meta- analysis is to determine if an intravesical or extravesical anastomosis in kidney transplantation is to be preferred . | We carried out a trial to evaluate the complication rate of intravesical ( LP ) versus extravesical ( Lich ) ureteroneocystostomy in recipients of renal transplantation . Ureteric stenosis was the predominant complication in the LP technique , which was more difficult to correct . Complications by the Lich technique were urinary leaks , which were managed successfully by prolonged bladder drainage . We conclude that the Lich technique is simpler to perform and avoids the complication of ureteric stenosis , and should therefore be the procedure of choice for ureteric implantation in recipients of renal transplants OBJECTIVE To determine whether the change from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis in renal transplantation has altered the incidence of urological complications . PATIENTS AND METHODS Data were retrieved from a prospect i ve computerized data base and by case-note review on 248 consecutive renal transplants performed between January 1990 and June 1996 . The characteristics of the donor . recipient and organ were noted , together with the technique used for the vesicoureteric anastomosis and the occurrence of major and minor urological complications . RESULTS The Leadbetter-Politano technique was used in 140 transplants and the stented extravesical technique in 108 . There were no significant differences in the donor , recipient or organ characteristics between the groups . The stented extravesical technique was associated with a significantly lower rate of major complications ( < 2 % ) and clinical ly significant haematuria than with the Leadbetter-Politano technique . CONCLUSION Changing from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis has been a major factor in reducing the incidence of urological complications in our transplant practice Abstract The incidence of urologic complications was studied in 131 patients with cadaver renal allografts allocated r and omly to undergo either the Politano-Leadbetter or end-to-side ureteroneocystostomy . Obstruction occurred in 6 per cent of patients with end-to-side versus 0 per cent of those with Politano-Leadbetter reconstructions ( p less than 0.05 ) . Complications of leakage , infection and graft loss were comparable in the 2 groups |
548 | 27,749,919 | Consumption of RTEC is associated with a healthier dietary pattern , concerning intake of carbohydrates , dietary fiber , fat and micronutrients , however total sugar intake is higher .
Persons consuming RTEC frequently ( ≥ 5 times/week ) have a lower risk of inadequate micronutrient intake especially for vitamin A , calcium , folate , vitamin B 6 , magnesium and zinc .
Evidence from prospect i ve studies suggests that whole grain RTEC may have beneficial effects on hypertension and type 2 diabetes .
Consumption of RTEC with soluble fiber helps to reduce LDL cholesterol in hypercholesterolemic men and RTEC fortified with folate can reduce plasma homocysteine .
Consumption of RTEC , especially of fiber-rich or whole grain RTEC , is implicated with several beneficial nutritional and health outcomes .
Of concern is the higher total sugar intake associated with frequent RTEC consumption | BACKGROUND In many countries breakfast cereals are an important component of breakfast .
This systematic review assesses the contribution of consumption of ready-to eat cereal ( RTEC ) to the recommended nutrient intake .
Furthermore , the effects of RTEC consumption on key health parameters are investigated as well as health promoting properties of RTEC . | A new guar-containing wheatflake product was developed to assess its effect on carbohydrate tolerance in normal-weight , healthy subjects . The extruded wheatflake breakfast cereals containing 0 ( control ) or approximately 90 g guar gum/kg DM were fed to ten fasting , normal-weight , healthy subjects using a repeated measures design . The meals were similar in energy ( approximately 1.8 MJ ) , available carbohydrate ( 78 g ) , protein ( 15 g ) and fat ( 5.4 g ) content . The guar gum content of the test meals was 6.3 g. Venous blood sample s were taken fasting and at 15 , 30 , 45 , 60 , 90 , 120 , 150 and 240 min after commencing each breakfast and analysed for plasma glucose , insulin and C-peptide . The guar wheatflake meal produced a significant main effect for glucose and insulin at 0 - 60 min and 0 - 240 min time intervals respectively , but not for the C-peptide levels compared with the control meal . Significant reductions in postpr and ial glucose and insulin responses were seen following the guar wheatflake meal compared with the control meal at 15 and 60 min ( glucose ) and 15 , 60 , 90 and 120 min ( insulin ) . The 60 and 120 min areas under the curve for glucose and insulin were significantly reduced by the guar gum meal , as was the 240 min area under the curve for insulin . Thus , it can be concluded that the use of a severe method of heat extrusion to produce guar wheatflakes does not diminish the physiological activity of the guar gum The effects of an enzyme-hydrolyzed arabinoxylan from wheat ( AXOS ) versus an intact arabinoxylan from flax ( FLAX ) added to a ready-to-eat cereal ( RTEC ) on the postpr and ial appetitive , hormonal , and metabolic responses in overweight women ( BMI 25.0–29.9 kg/m2 ) were evaluated . Subsequent meal energy intake was also assessed . Two r and omized , double-blind , crossover design studies were completed . For trial 1 , the participants consumed the following RTEC breakfast , matched for total weight and varied in energy content : low-fiber ( LF , 4 g ) ; high-fiber ( HF , 15 g ) as either AXOS or FLAX . For trial 2 , the participants consumed LF , HF-AXOS , and HF-FLAX RTECs but also consumed another LF breakfast that was isocaloric ( LF-iso ) to that of the HF breakfasts . Perceived appetite and blood sample s ( trial 2 only ) were assessed before and after breakfast . An ad libitum lunch was offered 4 h post-breakfast . No differences in postpr and ial appetite responses were observed among any breakfasts in either trial . The HF-AXOS and HF-FLAX led to increased postpr and ial GLP-1 and peptide YY ( PYY ) concentrations vs. LF-iso . No differences were observed in lunch meal energy intake among breakfast meals in either trial . Collectively , these data suggest that 15 g of low molecular weight fiber added to RTECs did not affect perceived appetite or subsequent energy intake despite differences in satiety hormone signaling in overweight females Background — Among adults , skipping meals is associated with excess body weight , hypertension , insulin resistance , and elevated fasting lipid concentrations . However , it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease ( CHD ) risk . The objective of this study was to prospect ively examine eating habits and risk of CHD . Methods and Results — Eating habits , including breakfast eating , were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer . During 16 years of follow-up , 1527 incident CHD cases were diagnosed . Cox proportional hazards models were used to estimate relative risks and 95 % confidence intervals for CHD , adjusted for demographic , diet , lifestyle , and other CHD risk factors . Men who skipped breakfast had a 27 % higher risk of CHD compared with men who did not ( relative risk , 1.27 ; 95 % confidence interval , 1.06–1.53 ) . Compared with men who did not eat late at night , those who ate late at night had a 55 % higher CHD risk ( relative risk , 1.55 ; 95 % confidence interval , 1.05–2.29 ) . These associations were mediated by body mass index , hypertension , hypercholesterolemia , and diabetes mellitus . No association was observed between eating frequency ( times per day ) and risk of CHD . Conclusions — Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals Objective : To test the hypothesis that a high carbohydrate breakfast with breakfast cereal leads to a meaningful reduction in dietary energy intake from fat , especially from saturated fat , and thus lower serum cholesterol levels . Design : An open r and omized controlled cross-over trial . The subjects were r and omized into intervention breakfast cereal or usual breakfast ( control ) groups . Setting : Free-living subjects aged 29–71 y in Eastern Finl and Subjects : 224 enrolled , 209 completed the study . The subjects were recruited from a survey of a r and om population sample and from other sources , and their serum cholesterol was not lower than 5.0 mmol/l . Recruited persons did not have any chronic disease or very low saturated fat intake . Intervention : The cereal group consumed 80 g ( men ) or 60 g ( women ) cereal at breakfast and the control group continued their usual dietary habits for six weeks . After a wash out of six weeks , a cross-over with another six week trial period took place . Measurements ( including serum sample s and a 3 d food record ) took place before and after the two trial periods . Results : The intervention period led to 2.5 en% ( energy percent units ) reduction in saturated fatty acids intake . The reduction in total fat intake was 5.5 en% . This was compensated for by increased intake of carbohydrates . The reduction in saturated fatty acids intake led to modest ( but in group 1 significant ) 0.15 mmol/l ( 2.5 % ) reduction in total serum cholesterol level . Conclusions : The trial showed that regular cereal breakfast can lead to reduced intake of total and saturated fatty acids of the daily diet and consequently to reduction in serum cholesterol level . Sponsorship : Supported by the Kellogg Company of Great Britain BACKGROUND Certain dietary components may play a role in the prevention of type 2 diabetes . OBJECTIVE We examined prospect ively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men . DESIGN Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 ( n = 42898 ) were followed for < /=12 y. Intakes of whole and refined grains , measured every 4 y by use of food-frequency question naires , were used to predict subsequent type 2 diabetes risk through multivariate analysis . RESULTS We ascertained 1197 cases of incident type 2 diabetes . After adjustment for age ; physical activity ; cigarette smoking ; alcohol consumption ; family history of diabetes ; and fruit , vegetable , and energy intakes , the relative risk of type 2 diabetes was 0.58 ( 95 % CI : 0.47 , 0.70 ; P for trend < 0.0001 ) comparing the highest with the lowest quintile of whole-grain intake . The association was moderately attenuated when additionally adjusted for body mass index ( relative risk : 0.70 ; 95 % CI : 0.57 , 0.85 ; P for trend = 0.0006 ) . Intake of refined grains was not significantly associated with risk of type 2 diabetes . After further adjustment for magnesium intake , cereal fiber intake , and glycemic load , the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant . CONCLUSIONS In men , a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber . Efforts should be made to replace refined-grain with whole-grain foods Epidemiological studies have shown an inverse association between dietary intake of whole grains and the risk of chronic disease . This may be related to the ability to mediate a prebiotic modulation of gut microbiota . However , no studies have been conducted on the microbiota modulatory capability of whole-grain ( WG ) cereals . In the present study , the impact of WG wheat on the human intestinal microbiota compared to wheat bran ( WB ) was determined . A double-blind , r and omised , crossover study was carried out in thirty-one volunteers who were r and omised into two groups and consumed daily 48 g breakfast cereals , either WG or WB , in two 3-week study periods , separated by a 2-week washout period . Numbers of faecal bifidobacteria and lactobacilli ( the target genera for prebiotic intake ) , were significantly higher upon WG ingestion compared with WB . Ingestion of both breakfast cereals result ed in a significant increase in ferulic acid concentrations in blood but no discernible difference in faeces or urine . No significant differences in faecal SCFA , fasting blood glucose , insulin , total cholesterol ( TC ) , TAG or HDL-cholesterol were observed upon ingestion of WG compared with WB . However , a significant reduction in TC was observed in volunteers in the top quartile of TC concentrations upon ingestion of either cereal . No adverse intestinal symptoms were reported and WB ingestion increased stool frequency . Daily consumption of WG wheat exerted a pronounced prebiotic effect on the human gut microbiota composition . This prebiotic activity may contribute towards the beneficial physiological effects of WG wheat BACKGROUND The glycemic index ( GI ) of a food is thought to directly reflect the rate of digestion and entry of glucose into the systemic circulation . The blood glucose concentration , however , represents a balance of both the entry and the removal of glucose into and from the blood , respectively . Such direct quantification of the postpr and ial glucose curve with respect to interpreting the GI is lacking in the literature . OBJECTIVE We compared the plasma glucose kinetics of low- and high-GI breakfast cereals . DESIGN On 2 occasions , plasma insulin concentrations and plasma glucose kinetics ( by constant-rate infusion of [6,6-(2)H(2)]glucose ) were measured in 6 healthy males for 180 min after they fasted overnight and then consumed an amount of corn flakes ( CF ) or bran cereal ( BC ) containing 50 g available carbohydrate . RESULTS The GI of CF was more than twice that of BC ( 131.5 + /- 33.0 compared with 54.5 + /- 7.2 ; P < 0.05 ) , despite no significant differences in the rate of appearance of glucose into the plasma during the 180-min period . Postpr and ial hyperinsulinemia occurred earlier with BC than with CF , result ing in a 76 % higher plasma insulin concentration at 20 min ( 20.4 + /- 4.5 compared with 11.6 + /- 2.1 micro U/mL ; P < 0.05 ) . This was associated with a 31 % higher rate of disappearance of glucose with BC than with CF during the 30 - 60-min period ( 28.7 + /- 3.1 compared with 21.9 + /- 3.1 micro mol . kg(-)(1 ) . min(-)(1 ) ; P < 0.05 ) . CONCLUSION The lower GI of BC than of CF was not due to a lower rate of appearance of glucose but instead to an earlier postpr and ial hyperinsulinemia and an earlier increase in the rate of disappearance of glucose , which attenuated the increase in the plasma glucose concentration BACKGROUND High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease , stroke , and dementia and are relatively common in older adults . OBJECTIVE We assessed the effect of breakfast cereal fortified with folic acid , vitamin B-6 , and vitamin B-12 on vitamin and homocysteine status . DESIGN A r and omized , double-blind trial was conducted in 189 volunteers aged 50 - 85 y. The subjects had no history of hypertension , anemia , asthma , cancer , or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal . Subjects were r and omly assigned to consume 1 cup ( 0.24 L ) breakfast cereal fortified with 440 microg folic acid , 1.8 mg vitamin B-6 , and 4.8 microg vitamin B-12 or placebo cereal for 12 wk . Blood was drawn at 0 , 2 , 12 , and 14 wk . Methionine-loading tests were conducted at baseline and week 14 . RESULTS Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group ( P < 0.001 ) . The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2 % to 0 % , with vitamin B-12 concentrations < 185 pmol/L from 9 % to 3 % , with vitamin B-6 concentrations < 20 nmol/L from 6 % to 2 % , and with homocysteine concentrations > 10.4 micromol/L ( women ) or > 11.4 micromol/L ( men ) from 6.4 % to 1.6 % . The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased . CONCLUSIONS In this relatively healthy group of volunteers , consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations , including post-methionine-load homocysteine concentrations BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women We evaluated the effect of high-fiber cereals on short-term food intake . At 0730 , 14 subjects ingested one of five cereals , plus milk and orange juice . At 1100 they were presented with a buffet lunch . There was a significant inverse correlation between fiber content of the cereals and energy intake at lunch . In a second study subjects ingested a very-high-fiber ( VHF ) cereal or a very-low-fiber ( VLF ) cereal . Fewer kcalories were ingested at lunch after ingestion of the VHF cereal than after ingestion of the VLF cereal . The degree of colonic microbial fermentation of the various cereals was evaluated by breath-hydrogen analysis . The higher-fiber cereals result ed in greater hydrogen production ; however , this may not influence energy intake . The results of question naires that asked about hunger indicated that food intake can be reduced without the perception of feeling less hungry . Thus , we found that cereals containing relatively large quantities of dietary fiber may decrease short-term food intake BACKGROUND Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse , and characterization of this association has been obscured by method ologic inconsistencies in the assessment of whole grains . OBJECTIVE We aim ed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men . DESIGN The study was conducted in a prospect i ve cohort of 27 082 men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were obtained periodically by using self-reported question naires , and participants measured and reported their body weight in 1986 and 1994 . RESULTS In multivariate analyses , an increase in whole-grain intake was inversely associated with long-term weight gain ( P for trend < 0.0001 ) . A dose-response relation was observed , and for every 40-g/d increment in whole-grain intake from all foods , weight gain was reduced by 0.49 kg . Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain ( P for trend = 0.01 ) , and , for every 20 g/d increase in intake , weight gain was reduced by 0.36 kg . Changes in cereal and fruit fiber were inversely related to weight gain . No associations were observed between changes in refined-grain or added germ consumption and body weight . CONCLUSIONS The increased consumption of whole grains was inversely related to weight gain , and the associations persisted after changes in added bran or fiber intakes were accounted for . This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain Soluble-fiber breakfast cereals were examined for their cholesterol-lowering ability in 58 male patients with mild to moderate hypercholesterolemia in a r and omized , double-blind , placebo-controlled study . Patients followed a step 1 diet for a minimum of 6 wk , then were r and omly assigned to groups incorporating either corn flakes or one of two soluble-fiber cereals ( pectin enriched or psyllium enriched ) in the diet for an additional 6 wk . During the diet-only phase , total cholesterol dropped 3.8 % . During the cereal-plus-diet phase , total and LDL cholesterol values of the pectin-enriched cereal group dropped an additional 2.1 % ( P = 0.243 ) and 3.9 % ( P = 0.16 ) , respectively , and they dropped 5.9 % ( P = 0.005 ) and 5.7 % ( P = 0.034 ) , respectively , in the psyllium-enriched cereal group . During the cereal-plus-diet phase , no significant effects on HDL cholesterol , triglyceride , or body weight were found within or between any cereal groups . These results support use of soluble-fiber cereals as an effective and well-tolerated part of a prudent diet in the treatment of mild to moderate hypercholesterolemia BACKGROUND Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight , little is known about the relation of whole grains to body weight and long-term weight changes . OBJECTIVE We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time . DESIGN In a prospect i ve cohort study , 74,091 US female nurses , aged 38 - 63 y in 1984 and free of known cardiovascular disease , cancer , and diabetes at baseline , were followed from 1984 to 1996 ; their dietary habits were assessed in 1984 , 1986 , 1990 , and 1994 with vali date d food-frequency question naires . Using multiple models to adjust for covariates , we calculated average weight , body mass index ( BMI ; in kg/m(2 ) ) , long-term weight changes , and the odds ratio of developing obesity ( BMI > or = 30 ) according to change in dietary intake . RESULTS Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains ( P for trend < 0.0001 ) . Over 12 y , those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber ( P for trend < 0.0001 ) independent of body weight at baseline , age , and changes in covariate status . Women in the highest quintile of dietary fiber intake had a 49 % lower risk of major weight gain than did women in the highest quintile ( OR = 0.51 ; 95 % CI : 0.39 , 0.67 ; P < 0.0001 for trend ) . CONCLUSION Weight gain was inversely associated with the intake of high-fiber , whole-grain foods but positively related to the intake of refined-grain foods , which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control BACKGROUND Prospect i ve studies evaluating associations between food intake and risk of heart failure ( HF ) in diverse population s are needed . OBJECTIVES Relationships between incident HF ( death or hospitalization ) and intake of seven food categories ( whole grains , fruits/vegetables , fish , nuts , high-fat dairy , eggs , red meat ) were investigated in an observational cohort of 14,153 African-American and white adults , age 45 to 64 years , sample d from four US communities . METHODS Between baseline ( 1987 - 1989 ) and Exam 3 ( 1993 - 1995 ) , dietary intake was based on responses to a 66-item food frequency question naire administered at baseline ; thereafter , intake was based on averaged baseline and Exam 3 responses . Hazard ratios ( HR [ 95 % CI ] ) for HF were calculated per 1-daily serving difference in food group intake . RESULTS During a mean of 13 years , 1,140 HF hospitalizations were identified . After multivariable adjustment ( energy intake , demographics , lifestyle factors , prevalent cardiovascular disease , diabetes , hypertension ) , HF risk was lower with greater whole-grain intake ( 0.93 [ 0.87 , 0.99 ] ) , but HF risk was higher with greater intake of eggs ( 1.23 [ 1.08 , 1.41 ] ) and high-fat dairy ( 1.08 [ 1.01 , 1.16 ] ) . These associations remained significant independent of intakes of the five other food categories , which were not associated with HF . CONCLUSIONS In this large , population -based sample of African-American and white adults , whole-grain intake was associated with lower HF risk , whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders Objective : To investigate the effect of a breakfast cereal containing inulin on blood lipids and colonic ecosystem in normolipidemic young men . Setting : Department of Food Science and Microbiology , University of Milan , Italy . Subjects : Twelve healthy male volunteers , age 23.3±0.5 y , body mass index ( BMI ) 25.7±1.2 kg/m2 ( mean±s.e.m . ) . Interventions : Subjects consumed daily , for three periods of four weeks , 50 g of a rice-based ready-to-eat cereal ( placebo ) and the same cereal containing 18 % inulin ( test ) in substitution of their habitual breakfast , then returned to the habitual diet ( wash-out ) . They followed no other dietary restrictions . Results : No changes in body weight , dietary habits , faecal and bile acid output , faecal short-chain fatty acid ( SCFA ) and faecal pH , were observed at the end of each period , whereas plasma total cholesterol and triacylglycerols significantly decreased at the end of test period by 7.9±5.4 ( P<0.05 ) and 21.2±7.8 % ( P<0.005 ) respectively . Meal glucose tolerance test ( MTT ) result ed in the same incremental area under the curve for both cereals ( IAUC test 124±35 ; placebo 118±33 mmol·min/l , ns ) . Inulin markedly enhanced breath H2 excretion ( IAUC test 280±40 ; placebo 78±26 ppm·h , P<0.005 ) , as well as faecal concentration of L-lactate . Total facultative anaerobes significantly decreased after test , and bifidobacteria increased after correction for total anaerobes ( P<0.05 ) . Changes in blood lipids were negatively correlated with bifidobacteria counts and positively with secondary bile acid excretion ( P<0.05 ) . Conclusions : Inulin seems to have a lipid lowering potential in normolipidemic men possibly mediated by mechanisms related to colonic fermentation . Sponsorship : National Research Council of Italy , grant number 95.00773.PF41 OBJECTIVES : To test ( 1 ) whether children will consume low-sugar ready-to-eat ( RTE ) cereals and ( 2 ) the effects of serving high- versus low-sugar cereals on the consumption of cereal , refined sugar , fresh fruit , and milk . PARTICIPANTS AND METHODS : Using an experimental design , we r and omly assigned children ( n = 91 ) who were attending summer day camp to receive a breakfast that included either the choice of 1 of 3 high-sugar cereals ( high-sugar condition ) or low-sugar cereals ( low-sugar condition ) , as well as low-fat milk , orange juice , bananas , strawberries , and sugar packets . Participants served themselves and completed a background question naire after eating . Research ers measured the amount and calories consumed of each food . RESULTS : In both conditions , children reported “ liking ” or “ loving ” the cereal they chose . Children in the low-sugar cereal condition consumed , on average , slightly more than 1 serving of cereal ( 35 g ) , whereas children in the high-sugar condition consumed significantly more ( 61 g ) and almost twice the amount of refined sugar in total ( 24.4 vs 12.5 g ) . Milk and total calories consumed did not differ significantly between conditions , but children in the low-sugar condition were more likely to put fruit on their cereal ( 54 % vs 8 % ) and consumed a greater portion of total calories from fresh fruit ( 20 % vs 13 % ) . CONCLUSIONS : Compared with serving low-sugar cereals , high-sugar cereals increase children 's total sugar consumption and reduce the overall nutritional quality of their breakfast . Children will consume low-sugar cereals when offered , and they provide a superior breakfast option BACKGROUND Studies from the West have demonstrated that ready-to-eat cereals ( RTECs ) are a common form of breakfast and more likely to be consumed by children . This study aim ed to investigate the breakfast eating pattern and RTECs consumption among schoolchildren in Kuala Lumpur . METHODS In this cross-sectional study , a total of 382 schoolchildren , aged 10 and 11 years old , were recruited from seven r and omly selected primary schools in Kuala Lumpur . Information on socio-demographics , breakfast eating patterns , and perceptions of RTECs and dietary intake ( 24-hour dietary recalls ) were obtained . RESULTS Among the respondents , only 22 % of them consumed breakfast on a regular basis . The most commonly eaten food by children at breakfast was bread ( 27.2 % ) , followed by biscuits ( 22.2 % ) and RTECs ( 20.5 % ) . The majority of them ( 93 % ) reported that they consumed RTECs sometimes during the week . Chocolate RTECs ( 34.1 % ) , corn flake RTECs ( 30.3 % ) , and RTECs coated with honey ( 25.1 % ) were the most popular RTECs chosen by children . Respondents who consumed RTECs showed a significantly higher intake in calories , carbohydrate , vitamin A , vitamin B1 , vitamin B2 , vitamin B3 , folate , vitamin C , calcium , iron , and fibre ( P < 0.05 ) , compared to those who skipped breakfast and those who had breakfast foods other than RTECs . CONCLUSION The lower levels of breakfast consumption among schoolchildren in Kuala Lumpur need serious attention . RTEC is a nutritious food which is well accepted by a majority of the schoolchildren in Kuala Lumpur . Nutrition intervention should be conducted in the future to include a well-balanced breakfast with the utilisation of RTECs for schoolchildren BACKGROUND Prospect i ve studies linking whole- and refined-grain intakes with the risk of hypertension , a major cardiovascular disease risk factor , remain limited . OBJECTIVE We aim ed to determine whether baseline intake of whole or refined grains is associated with subsequent development of hypertension . DESIGN We conducted a prospect i ve cohort study in 28 926 female US health professionals aged > or=45 y who were free of baseline cardiovascular disease , cancer , and hypertension in 1992 . Baseline whole- and refined-grain intakes were assessed from semiquantitative food-frequency question naires . We identified 8722 incident cases of hypertension from annual question naires during 10 y of follow-up . RESULTS After adjustment for known hypertension risk factors , the relative risks ( RRs ) ( and 95 % CIs ) of incident hypertension were 1.00 ( reference ) , 0.96 ( 0.89 , 1.03 ) , 0.95 ( 0.88 , 1.02 ) , 0.92 ( 0.85 , 0.99 ) , and 0.89 ( 0.82 , 0.97 ) across the increasing quintiles of baseline whole-grain intake ( P for trend = 0.007 ) . When functional cutoffs were used , women who consumed 0.5 to < 1 , 1 to < 2 , 2 to < 4 , and > or=4 whole-grain servings/d had multivariate RRs ( 95 % CIs ) of 0.93 ( 0.87 , 1.00 ) , 0.93 ( 0.87 , 0.99 ) , 0.92 ( 0.85 , 0.99 ) , and 0.77 ( 0.66 , 0.89 ) , respectively , compared with those who consumed < 0.5 whole-grain servings/d . In contrast , refined-grain intake was not associated with the risk of hypertension . The multivariate RRs of hypertension across the increasing quintiles of refined-grain intake were 1.00 , 0.97 , 0.94 , 0.99 , and 0.97 ( P for trend = 0.80 ) . CONCLUSION Higher whole-grain intake was associated with a reduced risk of hypertension in middle-aged and older women , which suggests a potential role for increasing whole-grain intake in the primary prevention of hypertension and its cardiovascular complications Background Dietary fibre food intake is related to a reduced risk of developing diabetes mellitus . However , the mechanism of this effect is still not clear . The aim of this study was to evaluate the effect of commercial fibre cereals on the rate of gastric emptying , postpr and ial glucose response and satiety in healthy subjects . Methods Gastric emptying rate ( GER ) was measured by st and ardized real time ultrasonography . Twelve healthy subjects were assessed using a r and omized crossover blinded trial . The subjects were examined after an 8 hour fast and after assessment of normal fasting blood glucose level . Satiety scores were estimated and blood glucose measurements were taken before and at 0 , 20 , 30 , 40 , 60 , 80 , 100 and 120 min after the end of the meal . GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 min after ingestion of sour milk with corn flakes ( GER1 ) , cereal bran flakes ( GER2 ) or wholemeal oat flakes ( GER3 ) . Results The median value was , respectively , 42 % for GER1 , 33 % for GER2 and 51 % for GER3 . The difference between the GER after ingestion of bran flakes compared to wholemeal oat flakes was statistically significant ( p = 0.023 ) . The postpr and ial delta blood glucose level was statistically significantly lower at 40 min ( p = 0.045 ) and 120 min ( p = 0.023 ) after the cereal bran flakes meal . There was no statistical significance between the areas under the curve ( AUCs ) of the cereals as far as blood glucose and satiety were concerned . Conclusion The result of this study demonstrates that the intake of either bran flakes or wholemeal oat flakes has no effect on the total postpr and ial blood glucose response or satiety when compared to corn flakes . However , the study does show that the intake of cereal bran flakes slows the GER when compared to oat flakes and corn flakes , probably due to a higher fibre content . Since these products do not differ in terms of glucose response and satiety on healthy subjects , they should be considered equivalent in this respect . Trial registration IS RCT BACKGROUND Prospect i ve data on the relation between whole grain intake and incident hypertension in men are limited , and no previous studies have quantitatively estimated total grams of whole grains in relation to risk of hypertension . OBJECTIVE The purpose of this study was to estimate the association of whole-grain intake ( g/d ) and risk of incident hypertension in a large prospect i ve cohort of men . DESIGN The Health Professionals Follow-Up Study is a prospect i ve cohort consisting of 51,529 male health professionals ranging in age from 40 to 75 y at enrollment in 1986 . Baseline and up date d measurement of whole-grain intake as well as important covariates were measured , and 31,684 participants without known hypertension , cancer , stroke , or coronary heart disease were followed prospect ively for 18 y through 2004 for onset of hypertension . RESULTS A total of 9227 cases of incident hypertension were reported over the 18 y of follow-up . In multivariate-adjusted analyses , whole-grain intake was inversely associated with risk of hypertension , with a relative risk ( RR ) of 0.81 ( 95 % CI : 0.75 - 0.87 ) in the highest compared with the lowest quintile ( P for trend < 0.0001 ) . In the multivariate model , total bran was inversely associated with hypertension , with a relative risk ( RR ) of 0.85 ( 95 % CI : 0.78 , 0.92 ) in the highest compared with the lowest quintile ( P for trend : 0.002 ) . CONCLUSIONS In summary , we found an independent inverse association between intake of whole grains and incident hypertension in men . Bran may play an important role in this association . These findings have implication s for future dietary guidelines and prevention of hypertension Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND In cohort studies , insoluble fiber has been associated with a reduced risk of obesity and diabetes ; however , compared with soluble fiber , its role in the regulation of short-term food intake ( FI ) and satiety has received little attention . OBJECTIVE Our aim was to compare the effects of a high-insoluble-fiber ( HF ) cereal with a low-fiber ( LF ) cereal on FI , subjective appetite ( SA ) , and plasma glucose ( PG ) in healthy individuals . DESIGN Males and females ( n = 32 ) were r and omly assigned to consume 60 g of either HF ( 26 g insoluble fiber , 120 kcal ) or LF ( 1 g fiber , 217 kcal ) breakfast cereal . Pre- and postlunch SA and PG were measured regularly for 4 h , and ad libitum FI was measured at 3 h. RESULTS The prelunch SA area under the curve did not differ between the 2 cereals , but when expressed as change in appetite per kilocalorie of cereal , HF suppressed SA more than did LF ( -17.6 + /- 1.8 compared with -10.0 + /- 1.1 mm . min . kcal(-)(1 ) , respectively ; P < 0.01 ) . Lunchtime FI did not differ between cereals , but cumulative energy intake ( cereal + lunch ) was lower after the HF than after the LF cereal ( 1330 + /- 57 compared with 1422 + /- 66 kcal , respectively ; P = 0.01 ) . The prelunch PG area under the curve ( P < 0.0001 ) and the immediate postlunch PG ( P = 0.01 ) were lower after HF cereal consumption . CONCLUSIONS An HF breakfast cereal contributes to a cumulative reduction in breakfast and lunch energy intake , possibly due to its high satiety value per kilocalorie . A short-term benefit of the HF cereal , compared with LF cereal , was lower PG concentration before and immediately after lunch OBJECTIVE The objective of this study was to compare the plasma glucose and insulin responses elicited by two ready-to-eat breakfast cereals ( one being high and the other being low in cereal fiber ) and to see if the differences in response depended on subjects ' fasting plasma insulin . RESEARCH DESIGN AND METHODS Nondiabetic men ( n = 77 ) were studied on two occasions after 10- to 14-h overnight fasts . They consumed 25 g of available carbohydrate from high- or low-fiber breakfast cereals in r and om order with blood taken at intervals for 2 h. Data from the 42 men with high fasting plasma insulin ( FPI ) on screening ( > 40 pmol/l ) were compared with those from the 35 men with normal FPI ( < or = 40 pmol/l ) . RESULTS Hyperinsulinemic men had significantly higher waist circumference and BMI , lower HDL cholesterol , and a trend toward higher triglycerides ( P = 0.07 ) than control subjects . In all 77 subjects , the incremental area under the glucose response curve ( AUC ) after high-fiber cereal was 11.8 + /- 5.5 % ( P = 0.036 ) less than after low-fiber cereal with the reductions being equivalent in the hyperinsulinemic ( 12.6 + /- 8.3 % ) and control ( 10.9 + /- 9.1 % ) groups . However , insulin peak rise was reduced by the high-fiber cereal only in hyperinsulinemic men ( 351 + /- 29 vs. 485 + /- 55 pmol/l ) but not in control subjects ( 211 + /- 20 vs. 220 + /- 20 pmol/l ; cereal x group interaction P = 0.044 ) . Insulin AUC after the high-fiber cereal , expressed as a percentage of that after low-fiber cereal , was negatively related to FPI ( P = 0.009 ) but not to age , BMI , or waist circumference . CONCLUSIONS The high-fiber cereal reduced glucose responses to the same extent in normal and hyperinsulinemic men , but reduced insulin responses only in hyperinsulinemic subjects Objective . To investigate the relationship between ready-to-eat ( RTE ) breakfast cereal consumption patterns and body mass index ( BMI ) , nutrient intake , and whole grain intake in an older American population . Design . A cross-sectional survey of US households , collected by the NPD Group via the National Eating Trends ( NET ) survey . Main outcome measures include BMI , nutrient intake , and whole grain intake . Subjects/ Setting . The sample included 1759 participants age 55 and older , which was divided into approximate quartiles based on intake of RTE breakfast cereal for the 2-week period ( 0 servings , 1–3 servings , 4–7 servings , and ≥8 servings ) . Results . In the multivariate linear regression analysis adjusted for energy and age ; intake of dietary fiber , whole grains , and the majority of micronutrients examined were found to be positively associated with frequent RTE cereal consumption . The proportion of participants consuming less than the Estimated Average Requirement ( EAR ) was lower for the highest quartile of RTE cereal consumers compared to nonconsumers , for the majority of vitamins and minerals examined . Significant differences in BMI between RTE breakfast cereal intake groups were found for men . Conclusion . Results suggest that ready-to-eat breakfast cereals may contribute to the nutritional quality of the diets of older Americans . Prospect i ve studies and experimental trials are needed to better evaluate the role of RTE cereal consumption in energy balance OBJECTIVE Prospect i ve studies have suggested that substituting whole grain for refined grain products may lower the risk of overweight and obesity . Breakfast cereal intake is a major source of whole and refined grains and has also been associated with having a lower BMI . The aim of this study was to prospect ively assess the association between whole and refined grain breakfast cereal intakes and risk of overweight ( BMI > or= 25 kg/m(2 ) ) and weight gain . RESEARCH METHODS AND PROCEDURES We examined 17,881 U.S. male physicians 40 to 84 years of age in 1982 who were free of cardiovascular disease , diabetes mellitus , and cancer at baseline and reported measures of breakfast cereal intake , weight , and height . RESULTS Over 8 and 13 years of follow-up , respectively , men who consumed breakfast cereal , regardless of type , consistently weighed less than those who consumed breakfast cereals less often ( p value for trend = 0.01 ) . Whole and refined grain breakfast cereal intake was inversely associated with body weight gain over 8 years , after adjustment for age , smoking , baseline BMI , alcohol intake , physical activity , hypertension , high cholesterol , and use of multivitamins . Compared with men who rarely or never consumed breakfast cereals , those who consumed > or=1 serving/d of breakfast cereals were 22 % and 12 % less likely to become overweight during follow-up periods of 8 and 13 years ( relative risk , 0.78 and 0.88 ; 95 % confidence interval , 0.67 to 0.91 and 0.76 to 1.00 , respectively ) . DISCUSSION BMI and weight gain were inversely associated with intake of breakfast cereals , independently of other risk factors Objectives : To examine if and how ready-to-eat cereals ( RTEC ) contribute to the quality of the diet of children , adolescents and young adults in a Mediterranean setting . Methods : A r and om sample of 3534 subjects aged 2 to 24 years in Spain was studied . Food and nutrient intakes were determined by a 24 hour recall . RTEC consumption was assessed by a quantitative food frequency question naire . Additional questions on socioeconomic level and nutritional knowledge were administered . Cereal consumption was classified into non-consumers and daily intakes between 1 and 20 g , 21 and 40 g , and more than 40 g . After excluding the underreporters the final sample consisted of 2852 individuals . Results : About half of the population ( 49.8 % ) reported eating RTEC . Macronutrient profile improved with increasing cereal consumption . Intakes of thiamine , riboflavin and vitamin B6 increased significantly with increasing consumption of RTEC in all age-sex groups , whereas niacin and folate intake improved in almost all groups and calcium , iron and vitamin D in at least half of the groups . Except for magnesium , vitamin B12 and vitamin E in males , consumption of RTEC was significantly associated with increased coverage of the daily nutrient requirements for all micronutrients studied . Higher levels of RTEC consumption was associated with a greater consumption of dairy products , and related to better breakfast quality . Conclusions : Level of RTEC consumption is associated with a better nutritional profile in the diets of Spanish children , adolescents and young adults and a lower risk for inadequate micronutrient intakes . RTEC consumers have better quality breakfasts , in terms of both food choices as well as energy and nutrient content OBJECTIVE To determine the cholesterol-lowering effect of ready-to-eat cereal containing soluble fibre as psyllium ( 86 % ) , oatmeal and barley on the plasma lipids of otherwise healthy men with mild hypercholesterolaemia , who were already eating a diet low in saturated fats . DESIGN Double-blind crossover trial , lasting 12 weeks , in volunteers eating each cereal for six weeks at home , in Sydney and Newcastle ( New South Wales ) . PARTICIPANTS Eighty-one men ( average age 50 years ; range , 31 - 69 years ) who had initial plasma ( total ) cholesterol concentrations of 5.8 - 8.8 mmol/L , but did not have major illness , obesity or diabetes , and were not on special diets or taking stool bulkers . INTERVENTION One box of cereal was eaten each day : control , 60 g wheat/wheat bran ( 2 g soluble fibre ) ; or test , 50 g of product containing psyllium/oats/barley ( 12 g soluble fibre ) . Subjects were allocated at r and om , when established on a low saturated fat diet , to wheat followed by psyllium cereal or psyllium followed by wheat cereal . MAIN OUTCOME MEASURES Plasma total cholesterol , high density lipoprotein cholesterol , triglyceride and low density lipoprotein cholesterol concentrations measured twice , four to seven days apart before the start of the trial and then after six weeks of eating each cereal . RESULTS Compliance was excellent with both cereals . There were no significant differences in subjects ' macronutrient intake or body weight between the two six-week periods . Total cholesterol and low density lipoprotein cholesterol concentrations fell significantly on psyllium cereal , relative to wheat cereal , in both periods at both centres ( mean -3.2 % and -4.4 % , respectively ) . There were no consistent changes in triglyceride or high density lipoprotein cholesterol concentrations . CONCLUSIONS This type of product , which is easy to consume on a daily basis , is a useful adjunct to the dietary management of mild hypercholesterolaemia OBJECTIVES This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus . METHODS We used a food frequency question naire for repeated dietary assessment s to prospect ively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984 . RESULTS During the 10-year follow-up , we confirmed 1879 incident cases of diabetes mellitus . When the highest and the lowest quintiles of intake were compared , the age and energy-adjusted relative risks were 0.62 ( 95 % confidence interval [ CI ] = 0.53 , 0.71 , P trend < .0001 ) for whole grain , 1.31 ( 95 % CI = 1.12 , 1.53 , P trend = .0003 ) for refined grain , and 1.57 ( 95 % CI = 1.36 , 1.82 , P trend < .0001 ) for the ratio of refined- to whole-grain intake . These findings remained significant in multivariate analyses . The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber , magnesium , and vitamin E. CONCLUSIONS These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus OBJECTIVE To examine sex differences and longitudinal changes in ready-to-eat ( RTE ) cereal and breakfast consumption in the Dietary Intervention Study in Children , and the relationship between RTE cereal intake with nutrient intake , blood lipids , and body mass index ( BMI ) . DESIGN Secondary analyses based on data from Dietary Intervention Study in Children , a r and omized , controlled , multicenter , clinical trial with five sets of three 24-hour recalls . SUBJECTS/ SETTING Children ( n=660 ) from six clinics aged 8 to 10 years at study entry . Participants had serum low-density lipoprotein cholesterol levels between the 80th and 98th percentiles for age , and were followed for a mean of 7.5 years . INTERVENTION Children were r and omized to a total fat- and saturated fat-modified dietary intervention or usual care . STATISTICAL ANALYSES Frequency of RTE cereal and breakfast consumption was examined by sex and age . Mixed models by sex were used to examine the relationship of RTE cereal consumption to average daily intake of nutrients , blood lipids , and BMI . RESULTS For all children , RTE cereal and breakfast consumption declined with age . Boys consumed RTE cereal more often compared with girls . Except for energy , RTE cereal consumption was positively associated with all measures of nutrients for both sexes . In boys , higher RTE cereal consumption was associated with lower total and low-density lipoprotein cholesterol levels and lower BMI . CONCLUSIONS Food and nutrition professionals should continue to educate youth and their parents on the nutritional benefits of routinely eating RTE cereal OBJECTIVES To investigate the relationship between plasma folate , vitamin B12 and total homocysteine concentrations , dietary intake of folate and vitamins B12 , B6 and B2 , and the risk of first acute myocardial infa rct ion ( MI ) . DESIGN Nested case-referent study with up to 13 years of follow-up . SETTING The population -based Northern Sweden Health and Disease Study , with 73 879 participants at the time of case ascertainment . SUBJECTS A total of 571 MI cases ( 406 men ) and 1569 matched referents . Of the cases , 530 had plasma sample s available , and 247 had dietary B-vitamin intake data . RESULTS Plasma concentrations of folate were inversely associated , and total homocysteine positively associated , with the risk of MI , independently of each other and of a number of established and novel cardiovascular risk factors , including renal function [ multivariate odds ratio for highest vs. lowest quintile of folate 0.52 ( 95 % CI 0.31 - 0.84 ) , P for trend = 0.036 , and homocysteine 1.92 ( 95 % CI 1.20 - 3.09 ) , P for trend = 0.006 ] . For plasma vitamin B12 concentrations , and vitamin B12 , B6 and B2 intake , no clear risk relationship was apparent . Though not statistically significant , the results for folate intake were consistent with those for plasma concentrations . CONCLUSIONS In this large prospect i ve study of a population without m and atory folic acid fortification , both folate and homocysteine were strongly associated with the risk of myocardial infa rct ion , independently of each other and of renal function . Although r and omized trials of folic acid supplementation are needed to determine causality , our findings highlight the potential importance of folate , or sources of folate , in incident cardiovascular disease BACKGROUND & AIMS The optimal dietary approach for weight loss and improving insulin sensitivity in adolescents is unknown . This study aim ed to explore the association between the estimated insulin dem and of the diet , as measured by glycemic and insulin load , weight loss , percentage body fat and insulin sensitivity index ( ISI ) in obese adolescents with clinical features of insulin resistance and /or prediabetes after a 3 month lifestyle and metformin intervention . METHODS Secondary data analysis of 91 adolescents ( median age 12.7 years ( range 10.1 - 17.4 ) participating in a r and omized controlled trial , known as RESIST ; ACTRN12608000416392 . Weight change between baseline and 3 months was measured by BMI expressed as percentage of the 95th centile ( BMI % 95 ) . Body composition was measured by dual energy X-ray absorptiometry and ISI was determined by an oral glucose tolerance test . RESULTS Higher dietary glycemic load and insulin load were associated with less weight loss ( BMI % 95 ) , adjusted for sex and pubertal stage , β = 0.0466 , P = 0.007 and β = 0.0124 , P = 0.040 , respectively . Inclusion of total energy intake in the model explained observed associations between dietary glycemic load and insulin load and change in BMI % 95 . Neither dietary glycemic load nor insulin load were associated with changes in percentage body fat or ISI . Dietary glycemic index and macronutrient content ( % of total energy ) were not associated to changes in BMI % 95 , percentage body fat or ISI . CONCLUSION Reduced energy diet contributes to weight loss in obese , insulin resistant adolescents . Diets with a lower insulin dem and were associated with a lower energy intake and may hence assist with weight loss BACKGROUND Heart failure ( HF ) is the leading cause of hospitalization among the elderly population in the United States . Consumption of grain products and dietary fiber has been shown to reduce the risk of hypertension and myocardial infa rct ion . However , it is not known whether a higher consumption of breakfast cereals is associated with risk of HF . METHODS This study evaluated prospect ively the association between breakfast cereal intake and incident HF among 21 376 participants of the Physicians ' Health Study I. Cereal consumption was estimated using a semiquantitative food frequency question naire . Incident HF was ascertained through annual follow-up question naires and vali date d using Framingham criteria . We used Cox regression models to estimate adjusted relative risk of HF across categories of cereal intake . RESULTS During an average follow-up of 19.6 years , 1018 incident cases of HF occurred . For average weekly cereal consumption of 0 servings , 1 or fewer , 2 to 6 , and 7 or more , hazard ratios ( 95 % confidence intervals ) for HF were 1 ( reference ) , 0.92 ( 0.78 - 1.09 ) , 0.79 ( 0.67 - 0.93 ) , and 0.71 ( 0.60 - 0.85 ) , respectively ( P<.001 for trend ) , adjusting for age , smoking , alcohol consumption , vegetable consumption , use of multivitamins , exercise , and history of atrial fibrillation , valvular heart disease , and left ventricular hypertrophy . However , the association was limited to the intake of whole grain cereals ( P < .001 for trend ) but not refined cereals ( P = .70 for trend ) . CONCLUSIONS Our data demonstrate that a higher intake of whole grain breakfast cereals is associated with a lower risk of HF . Additional studies are warranted to confirm these findings and determine specific nutrients that are responsible for such a protection Objective : Products enriched with oat β-glucan have been shown to reduce postpr and ial glucose and insulinemic responses . The aim of this study was to evaluate the effect of an extruded muesli product based on oat β-glucan on the rate of gastric emptying , postpr and ial blood glucose and satiety in healthy subjects . Methods : Gastric emptying rate ( GER ) was measured by st and ardized real-time ultrasonography . Twelve healthy subjects were assessed using a r and omized crossover double blind trial . The meals were administered after 8 hours ’ fasting after measuring the subject 's normal fasting blood glucose level . Blood glucose measurements were made before , 30 and 60 min after the end of the meal . Satiety scores were estimated 15 and 90 min after the end of the meal . The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of vanilla yoghurt with muesli containing 4 g oat β-glucan ( GER1 ) or vanilla yoghurt with muesli containing cornflakes ( GER2 ) . Results : The median values were 60 % for GER1 and 44 % for GER2 . The effect of 4 g oat β-glucan on the rate of gastric emptying was not statistically significant compared with corn flakes . Muesli with 4 g oat β-glucan lowered the postpr and ial glucose response significantly compared to the cornflakes meal ( p = 0.045 ) . The effect of oat β-glucan on satiety was not statistically significantly . Conclusions : The results of this study suggest that intake of muesli with 4 g oat β-glucan does not affect the gastric emptying rate or satiety but lowers the postpr and ial blood glucose response , indicating that the GER does not regulate the blood glucose level Objective : To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine ( tHcy ) . Design : Double-blind , r and omised placebo-controlled intervention trial . Setting : Community-based project in a New Zeal and city . Subjects : Seventy free living men and women with tHcy≥10 µmol/l . Mean age ( range ) was 58 ( 29–90 ) y. Interventions : Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified ( placebo ) or fortified with 100 , 200 or 300 µg folic acid . Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided . Main outcome measures : Plasma tHcy and serum folate concentrations . Results : Average serum folate concentrations ( 95 % CI ) increased significantly in the treatment groups relative to the control group by 28(9–51)% , 60(37–87)% and 79(51–114)% for supplementation with 100 , 200 and 300 µg folic acid , respectively . A reduction in tHcy was observed , being 16(8–22)% , 12(4–18)% and 17(9–24)% in the three treatment groups , respectively . Conclusions : A regular intake of as little as 100 µg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy . Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that , when aggregated from all sources , the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women . Funding : The breakfast cereals were supplied and the study partially funded by Kellogg Company OBJECTIVE To examine the association between breakfast cereal consumption and the risk of type 2 diabetes ( DM ) . RESEARCH METHODS AND PROCEDURES We analyzed prospect ively data from 21,152 male participants of the Physicians ' Health Study I. Consumption of breakfast cereals was estimated using an abbreviated food question naire , and incident DM was ascertained through yearly follow-up question naires . RESULTS The average age was 53.6 + /- 9.4 years ( range , 39.7 to 85.9 ) during the initial assessment of cereal intake ( 1981 to 1983 ) . During a mean follow-up of 19.1 years , 1958 cases of DM occurred . The crude incidence rates of DM were 57.7 , 53.8 , 43.5 , and 35.4 cases/10,000 person-years for people reporting breakfast cereal intake of 0 , < or=1 , 2 to 6 , and > or=7 servings/wk , respectively . In a Cox regression model adjusting for age , cigarette smoking , BMI , physical activity , vegetable consumption , and alcohol intake , hazard ratios ( 95 % confidence interval ) for DM were 1.0 ( reference ) , 0.89 ( 0.79 to 1.00 ) , 0.76 ( 0.67 to 0.86 ) , and 0.63 ( 0.55 to 0.72 ) from the lowest to the highest category of cereal consumption , respectively ( p for trend < 0.0001 ) . In secondary analyses , the inverse association between cereal intake and DM was stronger with whole-grain than refined cereals . DISCUSSION These results suggest that intake of breakfast cereals might confer a lower risk of DM . Consumption of whole-grain products may help lower the risk of DM Background : Ready-to-eat breakfast cereals ( RTE-BC ) are eaten more and more frequently by both adults and adolescents , but their nutritional quality is far from satisfactory : they often contained too much sugars and lead to a high glycemic index ( GI ) which generally contributes to a more rapid return of the feeling of hunger favouring nibbling in the morning . Objective : To reduce the GI and to improve the nutritional quality of st and ard wheat flakes ( SWF ) by adding a sourdough prefermentation step , suppressing steam cooking and decreasing the sucrose content ( MWF , modified wheat flake ) . Methods : Eleven healthy male volunteers were r and omly given , at three separate times , SWF , MWF , and white-wheat bread ( WWB , reference food ) . Plasma glucose , insulin and ghrelin concentrations were measured . The feeling of hunger was evaluated using a subjective rating scale . Starch structure of SWF and MWF was characterised by scanning electron microscopy . Results : GI of MWF ( 83 ± 7 ) was 12 % lower than that of SWF ( 94 ± 9 ) at 90 min but the effect was not significant . Insulinaemic index of MWF was significantly lower than that of SWF at 90 min ( 78 ± 6 vs 98 ± 8) . Hunger feelings were lower following MWF consumption and were positively correlated ( r = 0.98 ; P < 0.05 ) with plasma ghrelin concentrations , for which there was no significant difference between SWF and MWF . Starch granules of SWF were fully gelatinised unlike those of MWF . Conclusion : Despite its relatively high GI , MWF could provide health benefits by improving the management of hunger feeling in the morning and by moderately improving insulin economy , which could be of interest for type 2 diabetic subjects . GI is not , therefore , the sole parameter reflecting the nutritional quality of cereal products Objectives : To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine , an independent risk factor for occlusive vascular disease , in a general population . Design : A r and omized double-blind placebo-controlled intervention study .Subjects : One hundred and nineteen healthy volunteers , whose intake of fortified or supplemental folic acid was low , were recruited by letter from the patient register of a large inner-city group general practice . Methods : Volunteers were r and omized to receive unfortified cereals , or cereals fortified with 200 μg of folic acid per portion , with or without other vitamins . Blood sample s were taken presupplement and at 4 , 8 and 24 weeks on treatment and analysed for plasma homocysteine , cysteine and vitamin B12 and serum and red cell folate . Ninety-four subjects completed the study providing blood sample s on all four occasions . Results : There were no significant changes in any measured parameter in those eating unfortified cereals . Overall , folic acid fortification of cereals led to significant increases ( P<0.001 ) in serum folate ( 66 % ) , and red cell folate ( 24 % ) , and a decrease in plasma homocysteine ( 10 % ; P<0.001 ) . There were no changes in vitamin B12 or cysteine . The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate . Conclusions : If homocysteine is found to be a causative risk factor in occlusive vascular disease , food fortification with physiological levels of folic acid should have a significant impact on the prevalence of the disease in the general population .Sponsorship : We acknowledge , with thanks , financial support from the Kellogg Company of Great Britain OBJECTIVE : To report micronutrient intakes in Northern Irel and schoolchildren , and to establish the contribution of fortified breakfast cereal to overall nutrient intakes and achievement of current dietary recommendations . DESIGN : Analysis of dietary intakes and physical characteristics of participants in a r and omly selected 2 % population sample of 1015 schoolchildren aged 12 and 15 years in Northern Irel and during the 1990/1 school year . MAIN OUTCOME MEASURES : Dietary intakes , physical characteristics , and their association with consumption of fortified breakfast cereal . RESULTS : Mean micronutrient intakes were generally adequate with the exception of low intakes of folate ( boys and girls ) and iron ( girls ) . Fortified breakfast cereals , consumed by a high proportion ( 94 % boys ; 83 % girls ) of the sample , were associated with higher daily intakes of most micronutrients and fibre and with a macronutrient profile consistent with current nutritional recommendations . Appreciable proportions of subjects who did not consume fortified breakfast cereals had daily intakes that fell below the lower reference nutrient intake for riboflavin , niacin , folate , vitamin B-12 , and iron ( girls ) . CONCLUSIONS : The results demonstrate the potential of fortification in contributing to micronutrient intakes of schoolchildren , particularly where requirements are high , or for those on marginal diets of low nutritional quality BACKGROUND & AIMS Hypertension is a major public health problem . While many dietary factors affect the risk of developing hypertension , limited data are available on the association between consumption of breakfast cereal and incident hypertension . We examined the association between breakfast cereal consumption and the risk of hypertension . METHODS We prospect ively analyzed data from 13,368 male participants of the Physicians ' Health Study I. Consumption of breakfast cereals was estimated using an abbreviated food frequency question naire and incident hypertension was ascertained through yearly follow-up question naires . RESULTS The average age of study participants was 52.4 ± 8.9 years ( range 39.7 - 85.9 ) during the initial assessment of cereal intake ( 1981 - 1983 ) . During a mean follow up of 16.3 years , 7267 cases of hypertension occurred . The crude incidence rates of hypertension were 36.7 , 34.0 , 31.7 , and 29.6 cases/1000 person-years for people reporting breakfast cereal intake of 0 , ≤1 , 2 - 6 , and ≥7 servings/week , respectively . In a Cox regression model adjusting for age , smoking , body mass index , alcohol consumption , fruit and vegetable consumption , physical activity , and history of diabetes mellitus , hazard ratios ( 95 % CI ) for hypertension were 1.0 ( reference ) , 0.93 ( 0.88 - 0.99 ) , 0.88 ( 0.83 - 0.94 ) , and 0.81 ( 0.75 - 0.86 ) from the lowest to the highest category of cereal consumption , respectively ( p for trend < 0.0001 ) . This association was strongest for whole grain cereals and was observed in lean as well as overweight or obese participants . CONCLUSIONS The results of this longitudinal cohort study suggest that whole grain breakfast cereal consumption confers a lower risk of hypertension in middle-aged adult males Objective To examine associations between frequency of ready-to-eat-cereal ( RTEC ) consumption and cognitive function among elderly men and women of the Cache County Study on Memory Health and Aging in Utah . Design A population -based prospect i ve cohort study established in Cache County , Utah in 1995 . Setting and Participants 3831 men and women > 65 years of age who were living in Cache County , Utah in 1995.MeasurementDiet was assessed using a 142-item food frequency question naire at baseline . Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination ( 3MS ) at baseline and three subsequent interviews over 11 years . RTEC consumption was defined as daily , weekly , or infrequent use . Results In multivariable models , more frequent RTEC consumption was not associated with a cognitive benefit . Those consuming RTEC weekly but less than daily scored higher on their baseline 3MS than did those consuming RTEC more or less frequently ( 91.7 , 90.6 , 90.6 , respectively ; p-value < 0.001 ) . This association was maintained across 11 years of observation such that those consuming RTEC weekly but less than daily declined on average 3.96 points compared to an average 5.13 and 4.57 point decline for those consuming cereal more or less frequently ( p-value = 0.0009 ) . Conclusion Those consuming RTEC at least daily had poorer cognitive performance at baseline and over 11 years of follow-up compared to those who consumed cereal more or less frequently . RTEC is a nutrient dense food , but should not replace the consumption of other healthy foods in the diets ’ of elderly people . Associations between RTEC consumption , dietary patterns , and cognitive function deserve further study Homocysteine , a non-protein-forming sulfur amino acid , has attracted attention because elevated concentrations of circulating total homocysteine are associated with an increased risk for vascular disease ( 1 , 2 ) . Homocysteine is also a sensitive functional marker of inadequate cellular folate and vitamin B12 concentrations ( 3 ) . Inadequate status of these vitamins has important health consequences that may be independent of their role in homocysteine metabolism . Low folate concentrations increase a woman 's risk for having a baby with a neural tube defect ( 4 , 5 ) , and an inadequate vitamin B12 concentration is known to produce various neurologic and cognitive effects ( 6 , 7 ) . Persons with low circulating folate or vitamin B12 concentrations have higher fasting total homocysteine concentrations ( 8 - 10 ) , and elevated fasting total homocysteine concentrations are usually normalized by treatment with folic acid and vitamin B12 ( 6 , 11 - 14 ) . However , less is known about the importance of these vitamins as risk factors for high homocysteine concentration in the general population . Only three studies have examined the relation between homocysteine concentration and its vitamin determinants in sample s that were design ed to be representative of U.S. national ( 8) or regional ( 9 , 10 ) population s. One of these studies ( 9 ) reported that approximately two thirds of all cases of moderately elevated total homocysteine concentrations were potentially attributable to low vitamin concentrations , but estimation of the proportion of cases with high homocysteine concentrations that can be attributed to inadequate vitamin status is complicated by the lack of a st and ard definition of a high total homocysteine concentration . In the absence of a definition based on increased risk for an adverse health outcome , such as vascular disease , upper reference limits from sample s of healthy persons without established risk factors for high homocysteine concentrations have been used to define a high total homocysteine concentration ( 10 , 15 - 17 ) . We previously described the distribution of total serum homocysteine concentrations in participants 12 years of age or older from the third National Health and Nutrition Examination Survey ( NHANES III ) , a population -based sample of U.S. residents ( 18 ) . These data present a unique opportunity to develop population reference ranges for serum total homocysteine concentration and to determine the extent to which elevated homocysteine concentrations are associated with low circulating vitamin concentrations in a representative sample of U.S. residents . Methods Participants The NHANES III was developed to obtain nationally representative information on the health and nutritional status of the civilian , noninstitutionalized U.S. population ( 19 , 20 ) . Homocysteine concentrations were measured as part of an NHANES III surplus sera project on serum sample s from participants 12 years of age or older who were seen during phase II of this survey ( 19911994 ) . This project is described in greater detail elsewhere ( 18 ) . Homocysteine concentrations were measured at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University by using the high-performance liquid chromatography method of Araki and Sako ( 21 ) . The interassay coefficient of variation for this assay was 6 % . Folate and vitamin B12 were determined for phase 2 specimens at the Centers for Disease Control and Prevention central laboratory by using a Quanta Phase II radioassay kit ( Bio-Rad Laboratories , Hercules , California ) , and analyses are described in detail in the NHANES III Laboratory Procedures Manual ( 22 ) . The coefficients of variation for folate and vitamin B12 were 6 % and 7 % , respectively . Informed consent was obtained from all respondents . The NHANES III protocol was approved by the National Center for Health Statistics NHANES Institutional Review Board , and measurement of serum homocysteine was approved by the Human Investigations Review Committee at the New Engl and Medical Center . We used the following search strategy , combining Medical Subject Headings ( MeSH terms ) and text words , to identify all population -based studies relating vitamin status to circulating homocysteine concentrations : ( [ homocysteine ( MeSH ] OR homocysteine [ Text Word ] ) AND ( vitamins [ MeSH ] OR vitamin [ Text Word ] ] ) AND ( epidemiologic studies [ MeSH ] OR data collection [ MeSH ] OR survey [ Text Word ] ] . This search identified 137 citations , of which 16 were review s. We selected original studies that 1 ) were design ed to be representative of national , regional , or local population s and 2 ) described the relation between circulating homocysteine concentrations and either intake or circulating concentrations of folate or vitamin B12 . As of 1 March 1999 , 3 articles met our criteria ( 8 - 10 ) . Statistical Analysis We used sample weights in analyses to account for unequal probability of selection and nonresponse and to produce estimates of means and percentiles that were representative of the noninstitutionalized , civilian U.S. population . We used SUDAAN statistical software ( 23 ) to account for the complex survey design in the variance estimates . Because total homocysteine , folate , and vitamin B12 values were skewed , logarithmic transformations were applied . To show the relations between total homocysteine concentrations and vitamin concentrations , we classified participants into age- and sex-specific vitamin decile categories and estimated the geometric mean of the serum total homocysteine concentration within each decile . Analyses were adjusted for ethnicity and serum creatinine concentration . In addition , the relation between total homocysteine and folate concentrations was adjusted for vitamin B12 concentrations , and the relation between total homocysteine and vitamin B12 was adjusted for folate concentrations . We tested the associations between homocysteine and vitamins for interactions with age , sex , and ethnicity . We tested for trend of total homocysteine concentration across vitamin concentrations by using linear regression with the logarithm of the continuous vitamin concentration as the independent variable , adjusting as described above . We showed the trend by using the SYSTAT LOWESS procedure to fit smoothed curves ( 24 ) to the geometric mean total homocysteine concentrations in the vitamin decile categories ( 25 ) . It has been suggested that population reference ranges for the total homocysteine concentration be established in sample s of persons without established risk factors for a high homocysteine concentration ( 10 , 15 - 17 ) . For our reference sample , we included persons whom we assumed to be folate- and vitamin B12-replete ( that is , their serum concentrations of both vitamins were above the 50th percentile ) and had normal serum creatinine concentrations ( < 90 mol/L for women and < 110 mol/L for men ) . Pregnant women were excluded . We used the 5th and the 95th percentiles from the reference sample to estimate population reference ranges . To identify the potential impact of low vitamin concentrations on high total homocysteine concentration , we needed to establish values for high total homocysteine and low vitamin concentrations . We used the sex-specific 95th percentiles in the participants 20 to 39 years of age ( the reference sample ) to define high total homocysteine concentrations for all age groups . We used this reference sample because homocysteine concentrations changed little with age in this group , unlike in the other age groups ( 18 ) . We defined low vitamin concentrations as a folate concentration less than 11 nmol/L ( 26 , 27 ) and a vitamin B12 concentration less than 185 pmol/L ( 28 , 29 ) . We calculated the prevalence of high total homocysteine concentration ; the prevalence ratio for high total homocysteine concentration ; the attributable risk percentage ; and the population attributable risk percentage for persons with low concentrations of folate , vitamin B12 , or both compared with persons who had adequate concentrations of both of these vitamins . The attributable risk percentage estimates the excess cases of high homocysteine concentrations among persons with low vitamin concentrations , whereas the population attributable risk percentage takes into account the prevalence of low vitamin concentrations in the population and estimates the excess of high homocysteine concentrations associated with low vitamin concentrations in the entire population . We used the design effect for total homocysteine concentration , which is the ratio of the complex sampling design variance derived by using SUDAAN software ( 23 ) to the simple r and om sample variance calculated by using SAS software ( 30 ) , to determine the recommended minimum sample size needed to achieve stable estimates of means , proportions , and percentiles according to the National Center for Health Statistics analytic guidelines ( 19 ) . On the basis of an average design effect of approximately 1.4 for our sample , means and medians derived from fewer than 42 participants , 10th and 90th percentiles derived from fewer than 112 participants , and 5th and 95th percentiles derived from fewer than 224 participants were deemed unstable . Sample size for stable estimates of the proportions varied by the magnitude of the proportion , ranging from 42 for proportions of 0.5 to 224 for proportions of 0.05 or 0.95 . We indicate in the text and tables statistics that did not meet the appropriate sample size . We categorized participants into three ethnic groups : non-Hispanic white , non-Hispanic black , and Mexican American . We excluded persons from other ethnic groups ( n=436 ) because their inclusion produced unstable estimates of mean total homocysteine concentration after adjustment for ethnicity . Our analyses are based on 8086 participants with complete data on serum total homocysteine , folate , vitamin B12 , and creatinine concentrations . Results Table 1 shows selected characteristics of the sample by sex and ethnic group . On average , non-Hispanic white Background / Aims : To evaluate the metabolic effects of meals with varying glycemic index ( GI ) . Methods : We measured the glucose , insulin and leptin responses to two contrasting breakfast cereals in a group of 10 young healthy volunteers . Meals were provided on two separate occasions in r and om order after a 12-hour overnight fast , and consisted of 50 g of available carbohydrate from either Corn Flakes ( Kellogg ’s ) , or Fiber One ® ( General Mills ) . Blood sample s were obtained at rest , and 30 , 60 , 90 and 120 min after eating . The GI was calculated from the glucose response to the test meal normalized against a 50 g oral glucose load . Results : The GI for Corn Flakes was 125 ± 17 units and 49 ± 8 units for Fiber One ® . These meals were classified as high GI and low GI , respectively , and were significantly different from each other ( p < 0.0003 ) . The area under the insulin response curve ( AUC ) following the low glycemic meal was significantly attenuated compared to the high glycemic meal ( 14,064 ± 2,694 vs. 6,828 ± 1,182 pmol/l·min , p < 0.02 ) . The leptin AUC revealed that circulating leptin was suppressed by the high glycemic meal compared to the low ( 3.1 ± 1.5 vs. 9.6 ± 3.6 ng/ml·min , p < 0.04 ) . Conclusions : Lower insulin and higher leptin suggests that low glycemic meals promote a postpr and ial metabolic milieu that is favorable for reduced food consumption ; this may be advantageous in the control of obesity and related disorders including insulin resistance and type 2 diabetes Background : Puberty is a so-called critical period for overweight development and is characterized by physiological insulin resistance during mid-puberty . This study addressed the hypothesis that habitual consumption of a diet inducing higher levels of postpr and ial glycemia or insulinemia during puberty may have an unfavorable effect on the body composition in young adulthood . Methods : Multivariate regression analysis was performed on 262 participants of the Dortmund Nutritional and Anthropometric Longitudinally Design ed Study with at least two 3-day weighed dietary records during puberty ( baseline : girls 9–14 years ; boys 10–15 years ) and anthropometric measurements in young adulthood ( 18–25 years ) . A published dietary glycemic index was assigned to each carbohydrate-containing food . Similarly , each food was assigned a food insulin index ( insulinemic response to a 1 MJ portion of food relative to 1 MJ of glucose ) using 121 values measured at Sydney University . Results : Dietary glycemic index or glycemic load during puberty was not related to body composition in young adulthood . In contrast , a higher dietary insulin index and a higher dietary insulin load during puberty were associated with higher levels of percentage of body fat ( % BF ) in young adulthood , even after adjustment for early life , socioeconomic and nutritional factors ; % BF in energy-adjusted tertiles of dietary insulin index were 22.9 ( 95 % confidence intervals ( CI ) : 21.6 , 24.1 ) , 24.5 ( 23.2 , 25.7 ) , 24.7 ( 23.5 , 25.9 ) % , P for trend=0.01 ; % BF in energy-adjusted tertiles of dietary insulin load were 22.8 ( 95 % CI : 21.5 , 24.0 ) , 24.5 ( 23.2 , 25.7 ) , 24.8 ( 23.6 , 26.0 ) % , P for trend=0.01 . Adjustment for baseline % BF attenuated these relationships ( P for trend=0.1 and = 0.08 , respectively ) . Dietary insulin dem and was not related to body mass index . Conclusion : This study suggests a prospect i ve adverse influence of dietary insulin dem and during puberty on % BF in young adulthood . Postpr and ial increases in insulinemia rather than increases in glycemia appear to be implicated in an unfavorable development of body composition BACKGROUND The consumption of non-ready-to-eat cereal and ready-to-eat cereal ( RTEC ) breakfasts have been associated with increased nutrient intakes and lower body mass index ( BMI ) . These relationships have not been examined in low-income minority children . OBJECTIVES To evaluate , in low-income minority children , whether there is a relationship among the frequency of RTEC consumption and nutrient intakes measured at baseline , and whether there is a relationship between the frequency of RTEC and BMI controlling for age , sex , ethnicity , and energy intake . DESIGN A longitudinal study design where a cohort was followed for 3 years . SUBJECTS/ SETTING Participants were 625 fourth- through sixth- grade , low-income children living in San Antonio , Texas , and enrolled in the control arm of the Bienestar Diabetes Prevention Program 's cluster r and omized trial . Three multiple-pass 24-hour dietary recalls were collected at the beginning of their fourth- grade year and at the end of their fifth- and sixth- grade years . Children 's age , sex , ethnicity , and height and weight ( used to calculate BMI ) were collected between August 2001 and May 2004 . STATISTICAL ANALYSES PERFORMED Descriptive and inferential statistical analyses were performed . The frequency of breakfast consumption was examined using a 6 × 4 cross-tabulation table with χ(2 ) test to establish categorical differences . The degree of association between BMI percentile and frequency of RTEC consumption adjusted for age , sex , ethnicity , and nutrition-related parameters were calculated using a partial correlation multivariate linear model analysis . RESULTS There was a significant positive relationship between the frequency of RTEC consumption and nutrient intakes measured at baseline . There was also a significant inverse relationship between frequency of RTEC consumption and BMI percentile over the cumulative 3-year period controlling for age , sex , ethnicity , and energy intake . CONCLUSIONS Children who frequently consumed RTEC had greater intakes of essential nutrients at baseline and significantly lower BMI over a 3-year period |
549 | 25,089,377 | There was no evidence of publication bias or significant heterogeneity between subgroups on meta-regression analyses .
The results of this meta- analysis do not support an independent association between diets high in total fat and pancreatic cancer risk | Fat consumption has been hypothesized to influence pancreatic cancer risk , but the results of epidemiologic studies have been controversial .
We conducted a systematic review and meta- analysis of case-control and cohort studies to investigate this issue . | Aims /hypothesis . The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders . Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans . Methods . The KANWU study included 162 healthy subjects chosen at r and om to receive a controlled , isoenergetic diet for 3 months containing either a high proportion of saturated ( SAFA diet ) or monounsaturated ( MUFA diet ) fatty acids . Within each group there was a second assignment at r and om to supplements with fish oil ( 3.6 g n-3 fatty acids/d ) or placebo . Results . Insulin sensitivity was significantly impaired on the saturated fatty acid diet ( -10 % , p = 0.03 ) but did not change on the monounsaturated fatty acid diet ( + 2 % , NS ) ( p = 0.05 for difference between diets ) . Insulin secretion was not affected . The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion . The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median ( 37E % ) . Here , insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively ( p = 0.03 ) . Low density lipoprotein cholesterol ( LDL ) increased on the saturated fatty acid diet ( + 4.1 % , p < 0.01 ) but decreased on the monounsaturated fatty acid diet ( MUFA ) ( –5.2 , p < 0.001 ) , whereas lipoprotein ( a ) [ Lp(a ) ] increased on a monounsaturated fatty acid diet by 12 % ( p < 0.001 ) . Conclusions /interpretation . A change of the proportions of dietary fatty acids , decreasing saturated fatty acid and increasing monounsaturated fatty acid , improves insulin sensitivity but has no effect on insulin secretion . A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E % ) . [ Diabetologia ( 2001 ) 44 : 312–319 Meat contains numerous carcinogens , such as heterocyclic amines , polycyclic aromatic hydrocarbons , and N‐nitroso compounds , which can be derived either from natural food or during the process of food preparation . These carcinogens may increase pancreatic cancer risk . Furthermore , studies in animals showed that polyunsaturated fatty acids , especially linoleic acid , increase pancreatic cancer risk . We examined prospect ively the relation between pancreatic cancer risk and intake of fresh meat , processed meat , fish , eggs , total fat , and different types of fat . The Netherl and s Cohort Study consisted of 120,852 men and women who completed a baseline question naire in 1986 . After 13.3 years of follow‐up , 350 pancreatic cancer cases ( 66 % microscopically confirmed ) were available for analysis . A vali date d 150‐item food‐frequency question naire was used to calculate intake of fresh meat , processed meat , fish , eggs , fat and different types of fat . No association was found when examining the association between intake of fresh meat , other types of meat , fish , eggs , dietary intake of total fat and different types of fat and risk of pancreatic cancer . It is important for future studies to investigate the relation between different meat‐cooking methods and pancreatic cancer . © 2009 Case-control studies suggest that meat and cholesterol intakes may be related to elevated risks of pancreatic cancer . Few prospect i ve studies have examined associations between diet and pancreatic cancer , although in one recent study saturated fat consumption was related to higher risk . In a cohort of US women , the authors confirmed 178 pancreatic cancer cases over 18 years of follow-up . A mailed 61-item food frequency question naire was self-administered at baseline , and health and lifestyle variables were up date d biennially . Analyses were performed using Cox proportional hazards models to adjust for potential confounders . Intakes of total fat , different types of fats , and cholesterol were not associated with pancreatic cancer risk . Similarly , total meat , red meat , and dairy products were not related to risk . Individual food items contributing to intakes of total meat and dairy products , as well as fish and eggs , did not reveal any specific association . Updating dietary exposures by using question naires from 1980 , 1984 , 1986 , and 1990 produced similar findings . The authors ' data do not support previous findings that meat or saturated fat intakes are related to pancreatic cancer risk . Future prospect i ve studies should examine the influence of cooking practice s as well as other dietary habits on the risk of pancreatic cancer BACKGROUND Previous research relating dietary fat , a modifiable risk factor , to pancreatic cancer has been inconclusive . METHODS We prospect ively analyzed the association between intakes of fat , fat subtypes , and fat food sources and exocrine pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study , a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency question naire in 1995 - 1996 . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were calculated using Cox proportional hazards regression models , with adjustment for energy intake , smoking history , body mass index , and diabetes . Statistical tests were two-sided . RESULTS Over an average follow-up of 6.3 years , 865 men and 472 women were diagnosed with exocrine pancreatic cancer ( 45.0 and 34.5 cases per 100 000 person-years , respectively ) . After multivariable adjustment and combination of data for men and women , pancreatic cancer risk was directly related to the intakes of total fat ( highest vs lowest quintile , 46.8 vs 33.2 cases per 100 000 person-years , HR = 1.23 , 95 % CI = 1.03 to 1.46 ; P(trend ) = .03 ) , saturated fat ( 51.5 vs 33.1 cases per 100 000 person-years , HR = 1.36 , 95 % CI = 1.14 to 1.62 ; P(trend ) < .001 ) , and monounsaturated fat ( 46.2 vs 32.9 cases per 100 000 person-years , HR = 1.22 , 95 % CI = 1.02 to 1.46 ; P(trend ) = .05 ) but not polyunsaturated fat . The associations were strongest for saturated fat from animal food sources ( 52.0 vs 32.2 cases per 100 000 person-years , HR = 1.43 , 95 % CI = 1.20 to 1.70 ; P(trend ) < .001 ) ; specifically , intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk ( HR = 1.27 and 1.19 , respectively ) . CONCLUSION In this large prospect i ve cohort with a wide range of intakes , dietary fat of animal origin was associated with increased pancreatic cancer risk A case-control study was conducted in the Minneapolis-St Paul ( Minnesota , United States ) area to assess the role of dietary factors in the etiology of pancreatic cancer . Cases were White males aged 40 to 84 whose death certificate listed pancreatic cancer ( exocrine only ) . White male controls were ascertained through r and om-digit dialing . Family members were interviewed about the subject 's dietary usage in the two years prior to death ( cases , n=212 ) or prior to interview ( controls , n=220 ) . Energy-adjusted , nutrient-intake , risk estimates were calculated . Among all respondents , negative trends were observed for polyunsaturated fat , linoleic acid , vitamin C , and β-carotene . Positive trends were observed for riboflavin and retinol . Point estimates were , in general , comparable between the analyses of all respondents and spouse-only respondents . The nutrients associated with a decreased risk for pancreatic cancer occur primarily in vegetables and fruits , of which the consumption of cruciferous and β-carotene-rich vegetables and citrus fruits provided the greatest reduction in risk To examine the relation between diet and pancreatic cancer , we conducted a population -based case-control study in western Washington . Cases ( n = 148 ) were married men , aged 20 - 74 years , who were diagnosed with pancreatic cancer from July 1982 to June 1986 . Controls ( n = 188 ) , identified by r and om digit dialing , were frequency matched to the cases by 5-year age groups . Wives responded as surrogates for both cases and controls . Wives were interviewed by telephone , and they completed a mailed , self-administered food frequency question naire . Results indicated that pancreatic cancer risk increased with increasing protein intake . The increased risk for heavy consumers of protein was largely confined to individuals aged 65 years and above . In that group , the odds ratio for those in the highest quartile of protein intake , relative to the lowest , was 6.0 ( 95 % confidence interval 1.7 - 20.6 ) . No association was found between pancreatic cancer risk and the intake of total fat , saturated fat , cholesterol , omega-3 fatty acids , or vitamins A and C. There was an unexpected inverse association between calcium intake and pancreatic cancer risk in these data . These findings are discussed in relation to possible etiologic mechanisms that they suggest Background Few epidemiologic studies have examined the role of nutrient intake in the development of pancreatic cancer in Japan . We addressed this association in a population -based case-control study . Methods The cases were 109 patients who were newly diagnosed with pancreatic cancer between January 2000 and March 2002 , and controls were selected by a r and om procedure from the general population . Data on dietary intake were collected by in-person interview , with the use of a food-frequency question naire . The risk of pancreatic cancer associated with nutrient intake was estimated by using the odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) derived from a conditional logistic model . Results A statistically positive trend in risk was observed with increasing cholesterol intake , with subjects in the highest tertile experiencing a two fold increased risk ( OR , 2.06 ; 95 % CI , 1.11–3.85 ; Ptrend = 0.02 ) . Vitamin C intake was negatively associated with risk of pancreatic cancer . The OR was 0.45 ( 95 % CI , 0.22–0.94 ) for subjects in the highest tertile compared to the lowest tertile ( Ptrend = 0.04 ) . Conclusions Our study indicates that high cholesterol intake is significantly associated with an increased risk of pancreatic cancer and that high vitamin C intake decreases the risk of pancreatic cancer BACKGROUND Meat intake has been associated with risk of exocrine pancreatic cancer , but previous findings have been inconsistent . This association has been attributed to both the fat and cholesterol content of meats and to food preparation methods . We analyzed data from the prospect i ve Multiethnic Cohort Study to investigate associations between intake of meat , other animal products , fat , and cholesterol and pancreatic cancer risk . METHODS During 7 years of follow-up , 482 incident pancreatic cancers occurred in 190,545 cohort members . Dietary intake was assessed using a quantitative food frequency question naire . Associations for foods and nutrients relative to total energy intake were determined by Cox proportional hazards models stratified by gender and time on study and adjusted for age , smoking status , history of diabetes mellitus and familial pancreatic cancer , ethnicity , and energy intake . Statistical tests were two-sided . RESULTS The strongest association was with processed meat ; those in the fifth quintile of daily intake ( g/1000 kcal ) had a 68 % increased risk compared with those in the lowest quintile ( relative risk = 1.68 , 95 % confidence interval = 1.35 to 2.07 ; Ptrend < .01 ) . The age-adjusted yearly incidence rates per 100,000 persons for the respective quintiles were 41.3 and 20.2 . Intakes of pork and of total red meat were both associated with 50 % increases in risk , comparing the highest with the lowest quintiles ( both Ptrend < .01 ) . There were no associations of pancreatic cancer risk with intake of poultry , fish , dairy products , eggs , total fat , saturated fat , or cholesterol . Intake of total and saturated fat from meat was associated with statistically significant increases in pancreatic cancer risk but that from dairy products was not . CONCLUSION Red and processed meat intakes were associated with an increased risk of pancreatic cancer . Fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism because the findings for fat from meat and dairy products differed . Carcinogenic substances related to meat preparation methods might be responsible for the positive association Although mounting evidence suggests that insulin resistance is involved in pancreatic carcinogenesis , few epidemiologic studies have comprehensively investigated the role of lifestyle factors influencing this metabolic disorder in the etiology of pancreatic cancer . We sought to examine this problem in a case-control study conducted in 1994–1998 in Minnesota . Cases ( n = 186 ) , aged 20 yr or older , were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic ; from the latter , only cases residing in the Upper Midwest of the United States were recruited . Controls ( n = 554 ) were r and omly selected from the general population and frequency matched to cases by age ( within 5 yr ) and sex . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were estimated using unconditional logistic regression . After adjustment for confounders , physical activity was associated with a reduced risk , but this protective effect was confined to light activity and moderate activity only ( OR = 0.55 , 95 % CI = 0.30–0.97 , P trend = 0.038 and OR = 0.51 , 95 % CI = 0.28–0.93 , P trend = 0.07 , for highest vs. lowest quartile , respectively ) . An increased risk was found for dietary intakes of energy and fat but was statistically significant for saturated and polyunsaturated fat only . Of note , no appreciable difference in the magnitude of the associations existed between saturated , monounsaturated , and polyunsaturated fat . Compared with individuals in the lowest quartile of fiber intake , the risk was approximately halved for those in the third ( OR = 0.49 , 95 % CI = 0.26–0.94 ) and the highest quartile ( OR = 0.52 , 95 % CI = 0.21–1.30 ) . Our study lends support to the hypothesis that dietary and other lifestyle factors influencing insulin resistance modulate pancreatic cancer risk |
550 | 27,979,049 | Best Practice Advice 7 : Presence of systemic inflammatory response syndrome ( SIRS ) on admission is associated with an increased risk of multi‐organ failure ( MOF ) syndrome .
Methylprednisolone does not improve survival beyond 28 days , and the benefits for < 28 days are modest . | & NA ; The purpose of this clinical practice up date is to review diagnostic criteria for severe acute alcoholic hepatitis and to determine the current best practice s for this life‐threatening condition .
The best practice s in this review are based on clinical trials , systematic review s including meta‐ analysis and expert opinion to develop an approach to diagnosis and management .
Best Practice Advice 1 : Abstinence from drinking alcohol is the cornerstone of treatment for alcohol hepatitis ( AH ) .
Best Practice Advice 2 : Patients with jaundice and suspected AH should have cultures of blood , urine , and ascites , if present , to determine the presence of bacterial infections regardless of whether they have fever .
Development of MOF , usually due to infections developing after initial diagnosis of AH , is associated with a very high mortality rate . | BACKGROUND / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000 I.U. of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo . Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis BACKGROUND & AIMS Severe alcoholic hepatitis ( AH ) is a life-threatening disease for which adequate oral nutritional support is recommended . We performed a r and omized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH . METHODS We enrolled 136 heavy consumers of alcohol ( age , 18 - 75 y ) with recent onset of jaundice and biopsy-proven severe AH in our study , performed at 18 hospitals in Belgium and 2 in France , from February 2010 through February 2013 . Subjects were assigned r and omly ( 1:1 ) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone ( controls ) . In the intensive enteral nutrition group , enteral nutrition was given via feeding tube for 14 days . The primary end point was patient survival for 6 months . RESULTS In an intention-to-treat analysis , we found no significant difference between groups in 6-month cumulative mortality : 44.4 % of patients died in the intensive enteral nutrition group ( 95 % confidence interval [ CI ] , 32.2%-55.9 % ) and 52.1 % of controls died ( 95 % CI , 39.4%-63.4 % ) ( P = .406 ) . The enteral feeding tube was withdrawn prematurely from 48.5 % of patients , and serious adverse events considered to be related to enteral nutrition occurred in 5 patients . Regardless of group , a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died ( 65.8 % ; 95 % CI , 48.8 - 78.4 ) than patients with a higher intake of calories ( 33.1 % ; 95 % CI , 23.1%-43.4 % ) ( P < .001 ) . CONCLUSIONS In a r and omized trial of patients with severe AH treated with corticosteroids , we found that intensive enteral nutrition was difficult to implement and did not increase survival . However , low daily energy intake was associated with greater mortality , so adequate nutritional intake should be a main goal for treatment . Clinical Trials.gov number : NCT01801332 BACKGROUND & AIMS An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline ( PTX ) , an inhibitor of tumor necrosis factor ( TNF ) , in severe acute alcoholic hepatitis . The aim of the present study was to evaluate this treatment in a larger cohort of patients . METHODS One hundred one patients with severe alcoholic hepatitis ( Maddrey discriminant factor > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.29 ; 95 % confidence interval , 0.13 - 0.65 ) . Three variables ( age , creatinine level on r and omization , and treatment with PTX ) were independently associated with survival . TNF values on r and omization were not predictive of survival ; however , during the study period they increased markedly in nonsurvivors compared with survivors in both groups . CONCLUSIONS Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis . The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome . Increasing TNF levels during the hospital course are associated with an increase in mortality rate UNLABELLED Steroids improve the outcome in alcoholic hepatitis ( AH ) , but up to 40 % of patients fail to respond adequately . Interleukin-2 ( IL-2 ) exacerbates steroid resistance in vitro . We performed a prospect i ve study to determine if intrinsic steroid sensitivity correlates with response to steroids in individuals with severe AH and if IL-2 receptor blockade can reverse this . Peripheral blood mononuclear cells ( P BMC s ) were isolated from 20 patients with AH and a Maddrey 's score > 32 . Patients were treated with oral prednisolone plus full supportive measures . Clinical resistance to oral steroid treatment was defined as a drop in serum bilirubin of < 25 % within 7 days or death within 6 months . In vitro steroid resistance was measured in P BMC using the dexamethasone suppression of lymphocyte proliferation assay and repeated after the addition of the anti-IL-2 receptor ( anti-CD25 ) monoclonal antibody , basiliximab . Suppression of lymphocyte proliferation < 60 % was considered to indicate steroid resistance . In all , 82 % ( 9/11 ) of in vitro steroid-resistant patients were dead at 6 months as compared to 21 % ( 2/9 ) of steroid-sensitive patients ( P = 0.03 ) . Similarly , 91 % ( 10/11 ) of in vitro steroid-resistant patients failed to show a significant fall in bilirubin at day 7 as compared to 44 % ( 4/9 ) of steroid-sensitive patients ( P < 0.05 ) . Basiliximab improved the maximal proliferation count in 91 % ( 10/11 ) of in vitro steroid-resistant patients ( P = 0.003 ) . CONCLUSION Clinical outcome of steroid therapy in this patient cohort correlated with in vitro steroid resistance . IL-2 blockade improved in vitro steroid sensitivity . This suggests that intrinsic lack of steroid sensitivity may contribute to poor clinical response to steroids in severe AH . IL-2 receptor blockade represents a possible mechanism to overcome this Chronic obstructive pulmonary disease ( COPD ) is a common , progressive respiratory disease that causes great morbidity and mortality despite treatment . Tumor necrosis factor alpha ( TNF-alpha ) plays a central role as a pro-inflammatory cytokine in COPD . TNF-alpha release is markedly inhibited by phosphodiesterase type 4 ( PDE4 ) inhibitors that have proven efficacious in COPD clinical trials . The aim of this study was to compare the in vitro activities of the novel selective PDE4 inhibitors CI-1044 compared to well-known PDE4 inhibitors , rolipram and cilomilast , and to the glucocorticoid dexamethasone at reducing lipopolysaccharide (LPS)-induced TNF-alpha release in whole blood from COPD patients and healthy subjects . In the whole blood from COPD patients pre-incubation with PDE4 inhibitors or dexamethasone result ed in a dose-dependent inhibition of LPS-induced TNF-alpha release with IC(50 ) values of 1.3+/-0.7 , 2.8+/-0.9 microM , higher to 10 microM and lesser than 0.03 microM for CI-1044 , rolipram , cilomilast and dexamethasone , respectively . We observed a similar inhibition in the whole blood from healthy volunteers with , however , higher IC(50 ) values . These results indicate that CI-1044 inhibits in vitro LPS-induced TNF-alpha release in whole blood from COPD patients better than rolipram and cilomilast and suggested that it could be a useful anti-inflammatory therapy in COPD Two hundred eighty-one alcoholic patients were prospect ively evaluated by clinical , biochemical , and histologic parameters during a 4-yr period to assess their prognosis . They were stratified into four categories of injury : 1 ) fatty liver ( 26 patients ) , 2 ) acute alcoholic hepatitis ( 106 ) , 3 ) cirrhosis ( 39 ) , and 4 ) cirrhosis with superimposed alcoholic hepatitis ( 111 ) . The rate of survival and variables correlating with survival varied according to the group . At 48 months , 70 % of the patients with fatty liver were alive , 58 % in the alcoholic hepatitis group , 49 % in cirrhosis , and 35 % in alcoholic hepatitis superimposed upon cirrhosis . Within group one , deaths were due to causes unrelated to liver disease . In the alcoholic hepatitis group , factors significantly correlating with survival were ascites , alanine amino-transferase levels , grams of alcohol consumed , continuation of alcohol intake , and clinical severity of disease . Survival in patients of group three correlated significantly with prothrombin time and histologic severity score . Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis , with the most significant predictors of survival being age , grams of alcohol consumed , the ratio of serum aminotransferases ( AST : ALT ) and the histologic and clinical severity of the disease . Although a different pattern of correlates was observed for each pathologic level of injury , knowledge of the various correlates aids in prognostic assessment IMPORTANCE Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis , a life-threatening disease . The benefit of their combination is unknown . OBJECTIVE To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis , as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32 . Duration of follow-up was 6 months . The last included patient completed the study in October 2010 . None of the patients were lost to follow-up for the main outcome . INTERVENTION Patients were r and omly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day ( n=133 ) for 28 days , or 40 mg of prednisolone and matching placebo ( n=137 ) for 28 days . MAIN OUTCOMES AND MEASURES Six-month survival , with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model , which defines treatment nonresponders after 7 days of initiation of treatment . RESULTS In intention-to-treat analysis , 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups ( 69.9 % [ 95 % CI , 62.1%-77.7 % ] vs 69.2 % [ 95 % CI ; 61.4%-76.9 % ] , P = .91 ) , corresponding to 40 vs 42 deaths , respectively . In multivariable analysis , only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival . At 7 days , response to therapy assessed by the Lille model was not significantly different between the 2 groups ( Lille model score , 0.41 [ 95 % CI , 0.36 - 0.46 ] vs 0.40 [ 95 % CI , 0.35 - 0.45 ] , P = .80 ) . The probability of being a responder was not different in both groups ( 62.6 % [ 95 % CI , 53.9%-71.3 % ] vs 61.9 % [ 95 % CI , 53.7%-70.3 % ] , P = .91 ) . The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups ( 8.4 % [ 95 % CI , 4.8%-14.8 % ] vs 15.3 % [ 95 % CI , 10.3%-22.7 % ] , P = .07 ) . CONCLUSION AND RELEVANCE In patients with alcoholic hepatitis , 4-week treatment with pentoxifylline and prednisolone , compared with prednisolone alone , did not result in improved 6-month survival . The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome , which was less frequent in the group receiving pentoxifylline . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01214226 AIM To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis , and to evaluate the role of different liver function scores in predicting prognosis . METHODS Sixty-eight patients with severe alcoholic hepatitis ( Maddrey score > or = 32 ) received pentoxifylline ( n = 34 , group I ) or prednisolone ( n = 34 , group II ) for 28 d in a r and omized double-blind controlled study , and subsequently in an open study ( with a tapering dose of prednisolone ) for a total of 3 mo , and were followed up over a period of 12 mo . RESULTS Twelve patients in group II died at the end of 3 mo in contrast to five patients in group I. The probability of dying at the end of 3 mo was higher in group II as compared to group I ( 35.29 % vs 14.71 % , P = 0.04 ; log rank test ) . Six patients in group II developed hepatorenal syndrome as compared to none in group I. Pentoxifylline was associated with a significantly lower model for end-stage liver disease ( MELD ) score at the end of 28 d of therapy ( 15.53 + /- 3.63 vs 17.78 + /- 4.56 , P = 0.04 ) . Higher baseline Maddrey score was associated with increased mortality . CONCLUSION Reduced mortality , improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis BACKGROUND Role of corticosteroids in treatment of severe alcoholic hepatitis ( SAH ) is controversial . Pentoxifylline ( PTX ) , an inhibitor of TNF , has also been shown to decrease short term mortality in SAH . Aim of this study was to evaluate the effect of PTX on short term mortality , renal and hepatic functions in patients with SAH . METHODS Fifty patients with SAH { Maddrey 's Discriminant Function ( DF ) > or = 32 } were prospect ively enrolled . Twenty five patients received PTX ( 400 mg orally , three times a day ) , and 25 received placebo for 4 weeks . Serum tumor necrosis factor ( TNF ) was measured in both groups . RESULTS Baseline characteristics of the two groups were similar . At 4 weeks , mortality in PTX group was lower than that in controls { 20 % ( 5/25 ) versus 40 % ( 10/25 ) respectively ; p = 0.216 ; RR 0.5 ; 95 % CI 0.19 - 1.25}. Renal failure was the cause of mortality in 20 % ( 1/5 ) patients in PTX group , and 70 % ( 7/10 ) in controls ( p = 0.11 ) . Significant reduction in urea , creatinine , DF and TNF was noted in PTX group . Reduction in TNF did not correlate with reduction in creatinine or DF . CONCLUSIONS In patients with SAH , PTX leads to a significant improvement in renal and hepatic functions , and a trend towards decreased short term mortality OBJECTIVES : Prognostic stratification of patients with alcoholic hepatitis ( AH ) may improve the clinical management and facilitate clinical trials . We aim ed at developing a scoring system capable of providing prognostic stratification of patients with AH . METHODS : Patients with biopsy-proven AH were prospect ively included between 2000 and 2006 . The biochemical , clinical , portal hemodynamic and histological parameters were evaluated . A Cox regression model was used for univariate and multivariate analyses . A predictive score was built using variables obtained at admission identified in the multivariate analysis . The result ing score was vali date d in an independent prospect i ve cohort . RESULTS : In total , 103 patients with biopsy-proven AH were included in the study cohort . Age , serum bilirubin , serum creatinine , and international normalized ratio ( INR ) independently predicted 90-day mortality . We generated the Age , serum Bilirubin , INR , and serum Creatinine ( ABIC ) score : ( age × 0.1 ) + ( serum bilirubin × 0.08 ) + ( serum creatinine × 0.3 ) + ( INR × 0.8 ) . The area under the curve ( AUC ) was 0.82 . Using the Kaplan-Meier analysis with the cutoff values of 6.71 and 9.0 , we identified patients with low , intermediate , and high risk of death at 90 days ( 100 % , 70 % , and 25 % of survival rate , respectively ) . Using the same cutoff values , the ABIC score also stratified patients according to their risk of death at 1 yr . These results were vali date d by a confirmatory cohort ( N = 80 ) . CONCLUSIONS : The ABIC score is a new tool that allows the stratification of risk of death in patients with AH at 90 days and 1 yr . This score can help improve the management of these patients and also help to perform clinical trials BACKGROUND : Alcoholic hepatitis is a cause of major morbidity and mortality , and effective therapeutic regimens to treat this condition are lacking . Both experimental and clinical evidence indicates that tumor necrosis factor alpha ( TNF ) , and the downstream cytokine interleukin-6 ( IL-6 ) , correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis , thereby implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis . OBJECTIVE : The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor : FC fusion protein ( etanercept ) , an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial . METHODS : Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value greater than 15 and /or the presence of spontaneous hepatic encephalopathy . RESULTS : On an intention-to-treat basis , the 30-day survival rate of patients receiving etanercept was 92 % ( 12/13 ) . Adverse events that were encountered included infection , hepatorenal decompensation , and GI bleeding , which required premature discontinuation of etanercept in 23 % of patients ( 3/13 ) . CONCLUSIONS : This is the first study to examine TNF inhibition with etanercept in patients with alcoholic hepatitis and the results of this study support the rationale for larger controlled studies to further assess safety and efficacy Tumor necrosis factor-alpha ( TNF-alpha ) may contribute to the progression of acute alcoholic hepatitis ( AAH ) . The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH . Patients with severe AAH ( Maddrey score > /=32 ) were r and omly assigned to group A receiving intravenous infusions of infliximab ( 10 mg/kg ) in weeks 0 , 2 , and 4 ; or group B receiving a placebo at the same times . All patients received prednisolone ( 40 mg/day ) for 28 days . Blood neutrophil functional capacities were monitored over 28 days . After r and omization of 36 patients , seven patients from group A and three from group B died within 2 months . The probability of being dead at 2 months was higher ( not significant [ NS ] ) in group A ( 39 % + /- 11 % ) than in group B ( 18 % + /- 9 % ) . The study was stopped by the follow-up committee and the sponsor ( Assistance Publique-Hôpitaux de Paris ) . The frequency of severe infections within 2 months was higher in group A than in group B ( P < .002 ) . This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils . There were no differences between the two groups in terms of Maddrey scores at any time point . In conclusion , three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections BACKGROUND & AIMS Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies . Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-alpha ( TNF-alpha ) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis . A pilot study demonstrated that the TNF-alpha-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis . METHODS Forty-eight patients with moderate to severe alcoholic hepatitis ( Model for End-Stage Liver Disease score > or = 15 ) were enrolled and r and omized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks . Primary study end points included mortality at 1- and 6-month time points . RESULTS There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age , gender , and Model for End-Stage Liver Disease score . The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis ( 22.7 % vs 36.4 % , respectively ; OR , 1.8 ; 95 % CI , 0.5 - 6.5 ) . The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group ( 57.7 % vs 22.7 % , respectively ; OR , 4.6 ; 95 % CI , 1.3 - 16.4 ; P = .017 ) . Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group ( 34.6 % vs 9.1 % , respectively , P = .04 ) . CONCLUSIONS In patients with moderate to severe alcoholic hepatitis , etanercept was associated with a significantly higher mortality rate after 6 months , indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis BACKGROUND & AIMS In severe ( Maddrey score > or=32 ) alcoholic hepatitis ( AH ) , infection is classically viewed as a contraindication for corticosteroids , although specific data are lacking . This study 's aims were ( 1 ) to evaluate the incidence of infection in patients with severe AH before and after corticosteroid treatment ; ( 2 ) to determine whether infection contraindicates corticosteroids ; and ( 3 ) to focus on predictive factors of development of infection . METHODS At admission , systematic screening of infection consisted of chest x-ray and blood , ascites , and urinary cultures . All patients were treated with prednisolone . Response to steroids was defined using the Lille model . RESULTS Two hundred forty-six patients with severe AH were prospect ively included . Infections at admission were as follows : 63 infections ( 25.6 % ) were diagnosed : 28 ( 44.4 % ) spontaneous bacterial peritonitis or bacteremia , 8 ( 12.7 % ) pulmonary infections , 20 ( 31.7 % ) urinary tract infections , and 7 ( 11.2 % ) other infections . Patients infected before using corticosteroids had 2-month survival similar to that of others : 70.9 % + /- 6.1 % vs 71.6 % + /- 3.4 % , respectively , P = .99 . Development of infection after steroids : 57 patients ( 23.7 % ) developed infection : 16 ( 28.1 % ) spontaneous bacterial peritonitis or bacteremia , 23 ( 40.3 % ) pulmonary , 10 ( 17.5 % ) urinary tract , and 8 ( 14.1 % ) other infections . Infection occurred more frequently in nonresponders than in responders : 42.5 % vs 11.1 % , respectively , P < .000001 . In multivariate analysis , only the Lille model ( P = .0002 ) independently predicted infection upon steroids use . The Lille model ( P = .000001 ) and Model for End-Stage Liver Disease score ( P = .006 ) were independently associated with survival , whereas infection was not ( P = .52 ) . CONCLUSIONS Severe AH is associated with high risk of infection . Infection screening is warranted but should not contraindicate steroids . In terms of mechanisms , nonresponse to steroids is the key factor in development of infection and prediction of survival STUDY OBJECTIVE To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis . DESIGN R and omized , double-blind , placebo-controlled multicenter trial . SETTING Four university teaching hospitals . PATIENTS We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32 , calculated using the formula : 4.6 ( prothrombin time - control time ) + serum bilirubin [ in mumol/L]/17.1 . Fifty-nine patients ( 89 % ) completed the study . Two patients withdrew from the trial . The other 64 patients were hospitalized for the duration of the trial ; however , treatment was discontinued in 5 patients because of potential drug toxicity . INTERVENTIONS Patients were r and omly assigned to receive either methylprednisolone ( 32 mg ) or placebo within 7 days of admission . Treatment was given for 28 days . The doses were then tapered over 2 weeks and discontinued . MEASUREMENTS AND MAIN RESULTS The endpoint of the study was death . Of the 31 recipients of placebo , 11 ( 35 % ) died within 28 days of r and omization compared with 2 ( 6 % ) of the 35 patients given methylprednisolone ( P = 0.006 ) . The 95 % CI for the difference in mortality was 12 % to 70 % . In the patients with spontaneous hepatic encephalopathy at entry , 9 of 19 recipients of placebo died ( 47 % ) compared with 1 ( 7 % ) of the 14 patients given methylprednisolone ( P = 0.02 ) . The 95 % CI for the difference in mortality was 14 % to 66 % . The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables ( P = 0.004 ) . CONCLUSIONS Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value BACKGROUND & AIMS Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis . However , independent factors associated with a favorable outcome and long-term survival are unknown . The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis . METHODS Of 183 patients studied , 61 had been r and omized in a previous trial ; 32 of them were treated with prednisolone ( group I ) and 29 were not treated ( group II ) ; 61 were treated from the end of this r and omized trial ( group III ) ; and 61 were simulated ( group IV ) . RESULTS At 1 year , survival in group I ( 69 % ; confidence interval [ CI ] , 57%-81 % ) and group III ( 71 % ; CI , 55%-87 % ) was better than in the nontreated groups ( group II , 41 % ; CI , 23%-59 % ; P = 0.01 ) ( group IV , 50 % ; CI , 37%-63 % ; P = 0.05 ) . At 2 years , survival was not significantly different . Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival ( 76 % ; CI , 64%-88 % ) than the others ( 53 % ; CI , 35%-71 % ; P = 0.05 ) . Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival ( 77 % ; CI , 65%-89 % ) than the others ( 40 % ; CI , 14%-66 % ; P = 0.003 ) . In the 93 treated patients , liver polymorphonuclear infiltrate ( P < 0.03 ) and polymorphonuclear count ( P < 0.001 ) were independently correlated with 1-year survival . CONCLUSIONS Prednisolone reduced mortality by at least 1 year . Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors AIM To determine the effects of pentoxifylline , a methyl xanthine derivative on hepatic cell production of uninterferred lobe after portal vein branch ligation . METHODS Sixty-six rats were r and omly allocated into 9 groups with 8 rats in PVL groups and 6 rats in sham operation groups . The portal branches of the median and the lateral liver lobes , corresponding to approximately 70 % of the liver volume were ligated in the PVL groups . The control group received 0.9 % NaCl solution . The rats in the treatment groups received pentoxifylline at the dose of 50 mg/kg/dy . After 1 , 2 , 4 days of portal vein ligation in both PVL and PVNL lobes the levels of adenine nucleotides were determined and flowcytometric analysis of cell cycles were performed . RESULTS On the first day of portal branch ligation energy charge was significantly lower , in pentoxifylline treated group comparing to pentoxifylline untreated group , both in PVL and PVNL lobes ( P<0.05 ) . Proliferative indexes were 0.38 and 0.29 in pentoxifylline treated and pentoxifylline untreated PVNL lobes respectively ( P<0.05 ) . CONCLUSION Pentoxifylline treatment result ed in an increase of percentage of calls entering mitosis phase on the first day after PVL , somehow accelerating the regeneration process A multicenter r and omized 4-week interindividual double-blind study was carried out in 58 hospitalized patients with major depressive disorder ( DSM III 296.23 , 296.22 , 296.33 , 296.32 , 296.53 and 296.52 ) to test the dose-effect relationship of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram : 3 x 0.25 mg , 3 x 0.50 mg and 3 x 1.00 mg rolipram/day . With respect to the desired effect , the 3 x 0.50 mg dosage stood out from the others in almost all relevant parameters . With respect to the response rate , the efficacy of the 3 x 0.25 mg dosage was about the same as that reported in the literature for placebo . The inferior performance of the 3 x 1.00 mg dosage compared to the 3 x 0.50 mg dosage might indicate a reverse U-shaped dose-effect relationship . There was good tolerance to all three dosages . There were no findings that might cast doubt on the safety of the dosages tested BACKGROUND Mortality among patients with severe acute alcoholic hepatitis is high , even among those treated with glucocorticoids . We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival . METHODS We r and omly assigned 174 patients to receive prednisolone plus N-acetylcysteine ( 85 patients ) or only prednisolone ( 89 patients ) . All patients received 4 weeks of prednisolone . The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 ( at a dose of 150 , 50 , and 100 mg per kilogram of body weight in 250 , 500 , and 1000 ml of 5 % glucose solution over a period of 30 minutes , 4 hours , and 16 hours , respectively ) and on days 2 through 5 ( 100 mg per kilogram per day in 1000 ml of 5 % glucose solution ) . The prednisolone-only group received an infusion in 1000 ml of 5 % glucose solution per day on days 1 through 5 . The primary outcome was 6-month survival . Secondary outcomes included survival at 1 and 3 months , hepatitis complications , adverse events related to N-acetylcysteine use , and changes in bilirubin levels on days 7 and 14 . RESULTS Mortality was not significantly lower in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 27 % vs. 38 % , P = 0.07 ) . Mortality was significantly lower at 1 month ( 8 % vs. 24 % , P = 0.006 ) but not at 3 months ( 22 % vs. 34 % , P = 0.06 ) . Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 9 % vs. 22 % , P = 0.02 ) . In a multivariate analysis , factors associated with 6-month survival were a younger age ( P<0.001 ) , a shorter prothrombin time ( P<0.001 ) , a lower level of bilirubin at baseline ( P<0.001 ) , and a decrease in bilirubin on day 14 ( P<0.001 ) . Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group ( P = 0.001 ) ; other side effects were similar in the two groups . CONCLUSIONS Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis , 6-month survival , the primary outcome , was not improved . ( Funded by Programme Hospitalier de Recherche Clinique ; AAH-NAC Clinical Trials.gov number , NCT00863785 . ) UNLABELLED Early identification of patients with severe ( discriminant function > or = 32 ) alcoholic hepatitis ( AH ) not responding to corticosteroids is crucial . We generated a specific prognostic model ( Lille model ) to identify c and i date s early on for alternative therapies . Three hundred twenty patients with AH prospect ively treated by corticosteroids were included in the development cohort and 118 in its validation . Baseline data and a change in bilirubin at day 7 were tested . The model was generated by logistic regression . The model combining six reproducible variables ( age , renal insufficiency , albumin , prothrombin time , bilirubin , and evolution of bilirubin at day 7 ) was highly predictive of death at 6 months ( P < 0.000001 ) . The area under the receiver operating characteristic ( AUROC ) curve of the Lille model was 0.89 + /- 0.02 , higher than the Child-Pugh ( 0.62 + /- 0.04 , P < 0.00001 ) or Maddrey scores ( 0.66 + /- 0.04 , P < 0.00001 ) . In the validation cohort , its AUROC was 0.85 + /- 0.04 , still higher than the other models , including MELD ( 0.72 + /- 0.05 , P = 0.01 ) and Glasgow scores ( 0.67 + /- 0.05 , P = 0.0008 ) . Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others : 25 % + /- 3.8 % versus 85 % + /- 2.5 % , P < 0.0001 . This cutoff was able to identify approximately 75 % of the observed deaths . CONCLUSION In the largest cohort to date of patients with severe AH , we demonstrate that the term " nonresponder " can now be extended to patients with a Lille score above 0.45 , which corresponds to 40 % of cases . Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies Steroids are recommended in severe alcohol-induced hepatitis , but some data suggest that artificial nutrition could also be effective . We conducted a r and omized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients . A total of 71 patients ( 80 % cirrhotic ) were r and omized to receive 40 mg/d prednisolone ( n = 36 ) or enteral tube feeding ( 2,000 kcal/d ) for 28 days ( n = 35 ) , and were followed for 1 year or until death . Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition ( not significant ) . Eight enterally fed patients were prematurely withdrawn from the trial . Mortality during treatment was similar in both groups ( 9 of 36 vs. 11 of 35 , intention-to-treat ) but occurred earlier with enteral feeding ( median 7 vs. 23 days ; P = .025 ) . Mortality during follow-up was higher with steroids ( 10 of 27 vs. 2 of 24 intention-to-treat ; P = . 04 ) . Seven steroid patients died within the first 1.5 months of follow-up . In contrast to total enteral nutrition ( TEN ) , infections accounted for 9 of 10 follow-up deaths in the steroid group . In conclusion , enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis , although death occurs earlier with enteral nutrition . However , steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment , mainly because of infections . A possible synergistic effect of both treatments should be investigated BACKGROUND / AIMS Oxidative stress is putatively involved in the pathogenesis of alcohol-induced liver injury . This trial was devised to determine whether antioxidant therapy , alone or as an adjunct to corticosteroids , improved survival in patients with acute alcoholic hepatitis . METHODS Patients with a severe alcoholic hepatitis were stratified by sex and steroid use , and then r and omized . The active group received N-acetylcysteine for one week , and vitamins A-E , biotin , selenium , zinc , manganese , copper , magnesium , folic acid and Coenzyme Q daily for 6 months . The trial was double blinded and placebo controlled . The primary end-point was mortality within 6 months . RESULTS Thirty-six ( 20 male , 16 female ; mean discriminant function ( DF ) 86.6 ) received active drug , and 34 ( 18 male , 16 female ; mean DF 76.4 ) received placebo . 180-day survival was not significantly different between patients receiving drug and placebo ( 52.8 % vs. 55.8 % , p=0.699 ) . This was not affected by stratification for steroid use or sex . The only predictors of survival in multivariate analysis were initial bilirubin ( p=0.017 ) , white cell count ( p=0.016 ) and age ( p=0.037 ) . Treatment allocation did not affect survival in multivariate analysis ( p=0.830 ) . CONCLUSIONS Antioxidant therapy , alone or in combination with corticosteroids , does not improve 6-month survival in severe alcoholic hepatitis BACKGROUND Active nutrition therapy and the anabolic steroid ox and rolone ( OX ) , in selected patients with severe alcoholic hepatitis , significantly improved liver status and survival . We report here on the changes in their nutritional parameters . METHODS Protein energy malnutrition ( PEM ) was evaluated and expressed as percent of low normal in 271 patients initially , at 1 month and at 3 months . Active therapy consisted of OX plus a high caloric food supplement vs a matching placebo and a low calorie supplement . RESULTS PEM was present in every patient ; mean PEM score 60 % of low normal . Most of the parameters improved significantly from baseline on st and ard care ; the largest improvement seen in visceral proteins , the smallest in fat stores ( skinfold thickness ) . Total PEM score significantly correlated with 6 month mortality ( p = .0012 ) . Using logistic regression analysis , creatinine height index , h and grip strength and total peripheral blood lymphocytes were the best risk factors for survival . When CD lymphocyte subsets replaced total lymphocyte counts in the equation , CD8 levels became a significant risk factor ( p = .004 ) . Active treatment produced significant risk factor ( p = .004 ) . Active treatment produced significant improvements in those parameters related to total body and muscle mass ( ie , mid arm muscle area , p = .02 ; creatinine height index , p = .03 ; percent ideal body weight , p = .04 ) . CONCLUSION Deterioration in nutritional parameters is a significant risk factor for survival in severe patients with alcoholic hepatitis . This deterioration is reversible with st and ard hospital care . Active therapy further improves creatinine height index , mid arm muscle area and total lymphocyte counts . Hence , these later parameters appear to be the best indicators for follow-up assessment |
551 | 20,421,243 | First , when blinding fails research es can not determine whether any observed improvement in the group receiving active treatment result ed because of the treatment ’s effect or because of participants ’ expectancies .
Second , participant expectancies could create ceiling effects if there are strong placebo effects in each treatment arm and this may falsely suggest that the active treatment is ineffective without expectancy .
Third , the knowledge that a participant will be allocated active treatment or placebo in double-blind placebo-controlled RCTs is likely to lead to weaker treatment responses than would be expected in st and ard clinical practice , in which patients are unlikely to doubt that they have been given an active treatment .
Conclusions Participants ’ expectancies can undermine the validity of double-blind placebo-controlled RCTs . | Background R and omized controlled trials ( RCTs ) that use placebo controls to achieve double-blinding intend to establish the efficacy of a treatment over and above expectancy and other forms of bias .
Despite this , a growing body of research suggests that participant expectancies can influence the outcomes of these trials .
Purpose and Methods This non systematic review examines research assessing the role of participant expectancies in double-blind placebo-controlled RCTs in order to determine if and how they can limit these types of trials . | This study examined the accuracy of insomnia patients and their treating physicians in rating whether an active hypnotic drug or a placebo was given in treatment . Forty older adults with primary insomnia were r and omly assigned to either an active ( temazepam ) or a placebo condition using a double-blind strategy . Ratings of treatment conditions were obtained at 1 week ( early treatment ) , 4 weeks ( midtreatment ) , and 8 weeks ( late treatment ) . Patients were able to accurately discriminate ( beyond chance levels ) between the active and placebo medications at the early ( 76.9 % accuracy ) and late treatment assessment timepoints ( 78.1 % accuracy ) , but not at midtreatment ( 51.5 % accuracy ) . Therapists , however , were able to make accurate discriminations at the late treatment assessment timepoint only ( 80 % accuracy ) ; early ( 69.2 % accuracy ) and midtreatment ( 47.2 % accuracy ) ratings did not exceed chance levels . Patients who had used hypnotic drugs prior to this trial were more accurate in their judgments of treatment conditions than those without prior exposure . The findings raise an important issue about the internal validity of the double-blind strategy , which may in fact be only a single-blind procedure & NA ; Patient , provider , and clinical investigator expectations concerning treatments are believed to play important roles in patient response . This study examined the association of patient and research nurse/physician pretreatment expectations of pain relief with actual pain relief , the accuracy of patient and research nurse guesses about patient medication assignment , and changes in research nurse and patient pain relief expectations over the course of a r and omized double‐blind trial of amitriptyline versus an active placebo for patients with chronic pain and spinal cord injuries ( SCI ) . Patient expectations of pain relief with amitriptyline were associated significantly with actual pain decrease for patients in the amitriptyline , but not placebo , condition . Research nurse/physician expectations did not predict patient pain relief . Both patients and the research nurse were able to guess patient medication assignment at a rate significantly greater than chance . The research nurse 's , but not the patients ’ , expectations of pain relief with amitriptyline decreased significantly over the course of the study . These findings have implication s for future r and omized controlled trials . Fully double‐blind conditions are very difficult to achieve , and it is informative to assess patient and research clinician expectations and guesses regarding medication assignment Background : In r and omised controlled trials , an increasingly used test of the ‘ blindness ’ of assessors is to have them guess the group to which each participant has been allocated . Because assessors are usually aware of the trial hypotheses , we predicted that trial participants who showed the greatest improvement would be assumed by an assessor to have been in the ‘ preferred intervention ’ group . Methods : Data were derived from a trial in recent-onset rheumatoid arthritis comparing cognitive behavioural therapy plus routine care with routine care alone . Results : Although in this trial assessor blindness was demonstrated , patients ‘ guessed ’ by the assessor to be in the cognitive therapy group showed significantly greater improvements than those predicted to have received routine care alone in variables predicted to change in the study protocol . Conclusions : These results indicate that even if an assessor ’s guesses about patient group allocations are more accurate than expected by chance , this would not necessarily demonstrate failure of blinding . This casts further doubt on the validity of forced choice paradigms in testing the integrity of blinding in clinical trials & NA ; Individual differences in pharmacokinetics and pharmacodynamics , the type of pain and the method of drug administration can account for the response variability to analgesics . By integrating a clinical and an experimental approach , we report here that another important source of variability is represented by individual differences in non‐specific ( placebo ) activation of endogenous opioid systems . In the first part of this study , we analyzed the effectiveness of buprenorphine , tramadol , ketorolac and metamizol in the clinical setting , where the placebo effect was completely eliminated by means of hidden infusions . We found that the hidden injections were significantly less effective and less variable compared with open injections ( in full view of the subject ) , suggesting that part of the response variability was due to non‐specific factors ( placebo ) . Since we could not administer the opioid antagonist , naloxone , to these patients , in the second part of this study , we induced experimental ischemic arm pain in healthy volunteers and found that , as occurred in clinical pain , the analgesic response to a hidden injection of the non‐opioid ketorolac was less effective and less variable than an open injection . Most importantly , we obtained the same effects by adding naloxone to an open injection of ketorolac , thus blocking the opioid‐mediated placebo component of analgesia . These findings indicate that both the psychological ( hidden injection ) and pharmacological ( naloxone ) blockade of the placebo response reduce the effectiveness of , and the response variability to , analgesic drugs . Therefore , an important source of response variability to analgesics appears to be due to differences in non‐specific activation of endogenous opioid systems In this report , the authors explore the relationships of perceived treatment to outcome in a large , placebo-controlled trial of nicotine replacement treatment for smoking reduction . In the original study ( J. F. Etter , E. Laszlo , J. P. Zellweger , C. Perrot , & T. V. Perneger , 2002 ) , which was conducted in French-speaking Switzerl and , smokers were r and omly assigned to receive nicotine , matching placebo products , or no intervention . At the end of the 6-month study , participants were asked to guess whether they had received nicotine or placebo . In the present analysis , the authors examined the difference in smoking reduction between those who believed they had received nicotine and those who believed they had received placebo . Regardless of actual treatment , smokers who believed they had received nicotine had significantly better outcome than those who believed they had received placebo CONTEXT This study was part of a large double-blind sham surgery-controlled trial design ed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson 's disease . This portion of the study investigated the quality of life ( QOL ) of participants during the 1 year of double-blind follow-up . OBJECTIVES To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment ( the type of surgery patients thought they received ) . DESIGN Participants were r and omly assigned to receive either the transplant or sham surgery . Reported results are from the 1-year double-blind period . SETTING Participants were recruited from across the United States and Canada . Assessment and surgery were conducted at 2 separate university medical centers . PARTICIPANTS A volunteer sample of 40 persons with idiopathic Parkinson 's disease participated in the transplant ( " parent " ) study , and 30 agreed to participate in the related QOL study : 12 received the transplant and 18 received sham surgery . INTERVENTIONS Interventions in the parent study were transplantation and sham brain surgery . Assessment s of QOL were made at baseline and 4 , 8 , and 12 months after surgery . MAIN OUTCOME MEASURES Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes . We also investigated change over time . RESULTS There were 2 differences or changes over time in the transplant and sham surgery groups . Based on perceived treatment , or treatment patients thought they received , there were numerous differences and changes over time . In all cases , those who thought they received the transplant reported better scores . Blind ratings by medical staff showed similar results . CONCLUSIONS The placebo effect was very strong in this study , demonstrating the value of placebo-controlled surgical trials BACKGROUND Blinding can reduce bias in r and omized clinical trials , but blinding procedures may be unsuccessful . Our aim was to assess how often r and omized clinical trials test the success of blinding , the methods involved and how often blinding is reported as being successful . METHODS We analysed a r and om sample of blinded r and omized clinical trials indexed in the The Cochrane Central Register of Controlled Trials and published in 2001 . We identified 1599 blinded trials , and noted if they had conducted any test for the success of blinding . We also selected 200 trials r and omly that did not report any such test , and sent a question naire to the corresponding authors asking them if they had conducted any tests . RESULTS Thirty-one out of 1599 trials ( 2 % ) reported tests for the success of blinding . Test methods varied , and reporting was generally incomplete . Blinding was considered successful in 14 out of the 31 trials ( 45 % ) and unclear in 10 ( 32 % ) . Of the seven trials ( 23 % ) reporting unsuccessful blinding the risk of a biased trial result was either not addressed or was discounted in six cases . We received 130 question naires from trial authors ( 65 % ) of which 15 ( 12 % ) informed that they had conducted , but not published , tests . CONCLUSIONS Blinding is rarely tested . Test methods vary , and the reporting of tests , and test results , is incomplete . There is a considerable method ological uncertainty how best to assess blinding , and an urgent need for improved methodology and improved reporting Psychopharmacological studies usually attempt to eliminate " nonspecific " influences on outcome by double-blind design s. In a r and omized , double-blind comparison of alprazolam , imipramine , and placebo , the great majority of panic disorder patients ( N = 59 ) and their physicians were able to rate accurately whether active drug or placebo had been given . Moreover , physicians could distinguish between the two types of active drugs . Inasmuch as correct rating was possible halfway through treatment , concerns about the internal validity of the double-blind strategy arise This purpose of this article is to contrast the analgesic efficacy of acupuncture following dental surgery with the analgesic effects based on the expectation of benefit in two independently conducted placebo-controlled trials evaluating acupuncture as an adjunctive therapy for dental surgery . Both trials used pain following dental surgery as the outcome variable , and both included a blinding check to ascertain patients ’ beliefs regarding which treatment they were receiving . Although no statistically significant analgesic effect was observed between the acupuncture and placebo groups , participants in both experiments who believed they received real acupuncture reported significantly less pain than patients who believed that they received a placebo . Patients ’ beliefs regarding the receipt of acupuncture bore a stronger relationship to pain than any specific action possessed by acupuncture . These results also support the importance of both employing credible controls for the placebo effect in clinical trials and evaluating the credibility of those controls Heading Abstract Rationale . Critics have called into question findings from double-blind placebo-controlled studies because subjects are given drug administration instructions informing them of a placebo condition . The assertion that these drug administration instructions bias estimates of effectiveness has undergone surprisingly little empirical investigation . Objectives . The primary objective of this study was to determine whether drug administration instructions informing subjects of a placebo condition affect the drug response and affect the saliva concentration of the stimulant . Methods . We assessed caffeine responses and levels of saliva concentration of caffeine in 52 subjects who were r and omly assigned to receive one of two drug administration instructions : ( a ) placebo-informed instructions ( i.e. , individuals informed of the placebo ) analogous to those used in double-blind studies and ( b ) placebo-uninformed instructions ( i.e. , individuals informed they are taking an active stimulant ) . Results . On most measures ( systolic blood pressure , heart rate , h and steadiness , reaction time , fatigue , and tension ) , drug administration instructions did not significantly influence caffeine response . Instructions also had no significant effect on saliva concentration of caffeine . However , only individuals who were uninformed of the placebo condition showed significant diastolic blood pressure and vigor increases with 125 mg caffeine , and significant h and steadiness impairment and vigor increases with 325 mg caffeine compared to placebo . Conclusions . These overall findings suggest that a limited bias is introduced by drug administration instructions . The results do not support any suggestion that information about the existence of a placebo condition dramatically influences conclusions drawn about drug responses in placebo-controlled trials The objective of this study was to assess whether nicotine replacement therapy , administered in a real-life situation , could reduce cigarette consumption in smokers who were not prepared to quit smoking . Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and r and omly assigned to either a 6-month treatment of nicotine ( choice among a 15-mg nicotine patch , a 4-mg nicotine gum , a 10-mg nicotine inhaler , or a combination of these , N = 265 ) , matching placebo products ( N = 269 ) , or no intervention ( N = 389 ) . Products were sent to participants by mail . Education was limited to a booklet . Of 923 participants , 879 ( 95 % ) were followed up after 6 months . Mean baseline consumption was 30 cigarettes per day in all groups . At 6 months , cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group , 7.5 in the placebo group , and 2.5 among controls ( p < 0.04 for all pair-wise comparisons ) . Smoking cessation rates were low ( 2%–4 % ) and did not differ significantly between groups . Quit attempts were less frequent among controls ( 21 % ) than among the nicotine ( 28 % , p = 0.04 ) and placebo ( 27 % , p = 0.08 ) subjects . In conclusion , nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months , but a large part of this reduction was attributable to a placebo effect . Nicotine treatment for smoking reduction had no detectable impact on smoking cessation & NA ; Response expectancies have been proposed as the major determinant of placebo effects . Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice . Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days , together with a basal intravenous infusion of saline solution . However , the symbolic meaning of this basal infusion was changed in three different groups of patients . The first group was told nothing about any analgesic effect ( natural history ) . The second group was told that the basal infusion was either a powerful painkiller or a placebo ( classic double‐blind administration ) . The third group was told that the basal infusion was a potent painkiller ( deceptive administration ) . Therefore , whereas the analgesic treatment was exactly the same in the three groups , the verbal instructions about the basal infusion differed . The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three‐days treatment . We found that the double‐blind group showed a reduction of buprenorphine requests compared to the natural history group . However , this reduction was even larger in the deceptive administration group . Overall , after 3 days of placebo infusion , the first group received 11.55 mg of buprenorphine , the second group 9.15 mg , and the third group 7.65 mg . Despite these dose differences , analgesia was the same in the three groups . These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects , which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake There is ongoing debate about whether r and omized , placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants . Numerous meta-analyses of antidepressant efficacy trials , e.g. , Kirsch et al. [ Kirsch , I. , Moore , T. J. , Scoboria , A. , & Nicholls , S. ( 2002 ) . The emperor 's new drugs : An analysis of antidepressant medication data su bmi tted to the U.S. food and drug administration . Prevention and Treatment , 5 , Article 23 . ( Retrieved July 19 , 2007 from http://journals.apa.org/prevention/volume5 ) ] , have shown a modest drug-placebo difference but method ological problems with st and ard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded . St and ard trial design assumes the additivity thesis of pharmacological efficacy , being the assumption that the specific or " true " magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a st and ard trial . If the drug effects are as small as these meta-analyses suggest , then their clinical effectiveness is question able . If the drug effects are actually larger but masked by placebo effects , then the additivity thesis is not valid and we risk false negative results with st and ard trial design . Kirsch et al. propose an alternative , four arm balanced placebo trial design ( BPTD ) that can accurately test the additivity thesis . The BPTD uses antidepressants , active placebos and the intentional deception of research subjects . My focal question is whether the BPTD is ethically defensible . I will explore two objections that can be raised against it : 1 ) lying to BPTD research subjects violates their autonomy and exploits their illness and 2 ) the BPTD may not enable us to test the additivity thesis with accuracy , i.e. , it may contribute to the masking of drug effects that it aims to avoid . I argue that these objections support the conclusion that the BPTD is ethically indefensible Abstract In a pooled analysis of four r and omized controlled trials of acupuncture in patients with migraine , tension‐type headache , chronic low back pain , and osteoarthritis of the knee we investigated the influence of expectations on clinical outcome . The 864 patients included in the analysis received either 12 sessions of acupuncture or minimal ( i.e. sham ) acupuncture ( superficial needling of non‐acupuncture points ) over an 8 week period . Patients were asked at baseline whether they considered acupuncture to be an effective therapy in general and what they personally expected from the treatment . After three acupuncture sessions patients were asked how confident they were that they would benefit from the treatment strategy they were receiving . Patients were classified as responders if the respective main outcome measure improved by at least fifty percent . Both univariate and multivariate analyses adjusted for potential confounders ( such as condition , intervention group , age , sex , duration of complaints , etc . ) consistently showed a significant influence of attitudes and expectations on outcome . After completion of treatment , the odds ratio for response between patients considering acupuncture an effective or highly effective therapy and patients who were more sceptical was 1.67 ( 95 % confidence interval 1.20–2.32 ) . For personal expectations and confidence after the third session , odds ratios were 2.03 ( 1.26–3.26 ) and 2.35 ( 1.68–3.30 ) , respectively . Results from the 6‐month follow‐up were similar . In conclusion , in our trials a significant association was shown between better improvement and higher outcome expectations OBJECTIVE Administration of the muscle relaxant carisoprodol and placebo was crossed with information that was agonistic or antagonistic to the effect of carisoprodol . It was investigated whether information alone induced physiological and psychological responses , and whether information modified the response to the drug . METHODS Half of the subjects received capsules containing 525 mg carisoprodol together with information that the drug acted in a specific way ( Groups Relaxant/C , Stimulant/C , and No Information/C ) . The other half of the subjects received lactose ( Groups Relaxant/L , Stimulant/L , and No Information/L ) . Dependent variables were blink reflexes and skin conductance responses , subjective measures of tension and sleepiness , and serum carisoprodol and meprobamate concentrations . Recordings were made between 15 and 130 minutes after administration of the capsules . RESULTS The Stimulant/L group reported more tension compared with the other two groups , and carisoprodol increased tension even more in the Stimulant/C group . The Relaxant/C group displayed higher levels of carisoprodol serum concentration compared with the other groups that received carisoprodol . CONCLUSIONS Reported tension was modulated in the direction suggested by the stimulant information . The effect of carisoprodol on tension was also modulated by stimulant information . Increased carisoprodol absorption in the group that received relaxant information could be a mechanism in the placebo response To determine the relative effects of expectancy and nicotine depletion on aversive withdrawal symptoms , we gave 109 smokers attempting to quit either nicotine gum or placebo within a balanced placebo design and monitored their withdrawal symptoms and smoking for 2 weeks . Subjects who believed they were getting nicotine gum reported less physical symptoms of withdrawal , showed less arousal , and smoked fewer cigarettes during the first week of quitting when compared with those who thought they were receiving placebo gum . The actual nicotine content of gum had no effect on withdrawal or relapse Introduction In double-blind r and omized placebo-controlled trials ( RCT ) of therapeutic interventions , the effects of the treatment may provide feedback that undermines blinding and consequently distorts measures of the effectiveness of the intervention . Methods and Results This possibility was confirmed in an experimental model using a dummy placebo procedure whereby participants were led to believe that they were taking part in testing a cognitive-enhancing drug . In two experiments , false feedback given about cognitive performance influenced participants ’ beliefs about whether they had been allocated to the active treatment or placebo . These beliefs also appeared to influence actual cognitive performance in that participants who believed they had taken the active treatment had higher accuracy in Experiment 1 and faster reaction times in Experiment 2 than those who believed they had been given a placebo . The addition of no treatment control groups in Experiment 2 showed that these effects could not be accounted for by the feedback manipulation itself , thereby supporting expectancy as a causal factor . Discussion These results indicate the importance of assessing participants ’ beliefs about their treatment allocation in real double-blind RCTs and considering if and how these may have affected the trial ’s outcome Subjects were given varying doses of a placebo , consisting of decaffeinated coffee , with double-blind or deceptive instructions . Deceptive administration simulated clinical situations in that subjects were led to believe that they were receiving an active drug . In contrast , subjects in double-blind conditions were aware that they might receive a placebo . Double-blind and deceptive administration of the placebo produced different , and in some instances , opposite effects on pulse rate , systolic blood pressure , and subjective mood . Deceptive administration produced an increase in pulse rate , whereas double-blind administration did not . A theoretically predicted curvilinear effect on systolic blood pressure , alertness , tension , and certainty of having consumed caffeine was confirmed with deceptive administration , but not with double-blind administration . Double-blind administration produced curves in the opposite direction on each of these variables . The effects of the placebo on motor performance varied as a function of subject 's beliefs about the effects of caffeine . These data challenge the validity of double-blind experimental design s and suggest that this common method of drug assessment may lead to spurious conclusions Background The double-blind placebo-controlled design is commonly considered the gold st and ard in research methodology ; however , subject expectation bias could subvert blinding . Objective The primary aim of this study was to examine the impact of expectation bias . Specifically , we examined perceived treatment assignment on smoking cessation outcome rates among participants enrolled in a clinical trial of bupropion ( 150 mg SR , BID ) . Design Analyses were conducted on data collected during “ Kick It at Swope , ” a double-blind , placebo-controlled , r and omized trial of 600 African-American smokers . Chi-square and multiple logistic regression analyses were used to examine the impact of perception of assignment on treatment effect and cotinine-verified smoking abstinence rates . Participants Participants were predominantly middle-aged ( mean 44.7 , SD 11.2 ) , African-American women ( 68.6 % ) , who smoked 19 CPD ( SD = 8.1 ) . Most had completed at least a high school education or GED ( 51.6 % ) , and 55 % had a monthly family income < $ 1,800 . Measurements At week 6 ( end of treatment ) and week 26 ( end of study ) , participants were asked to report their perceived treatment group assignment . Self-reported abstinence ( weeks 6 and 26 ) was confirmed using CO and cotinine biochemical verification . Results After adjusting for actual treatment assignment , age and baseline cotinine , participants who perceived being assigned to bupropion vs. placebo were more likely to be abstinent at weeks 6 ( OR = 2.07 , 95 % CI : 1.29 to 3.33 , p = 0.002 ) and 26 ( OR = 1.85 , 95 % CI : 1.05 to 3.24 , p = 0.032 ) . Conclusions Results support previous research that expectation bias associated with judgment of treatment assignment is a strong predictor of outcome and confirms this relationship in a smoking cessation trial using bupropion SR among African-American smokers The purpose of the double blind is to protect the internal validity of a clinical trial by preventing knowledge of treatment conditions from influencing outcome or its assessment . We studied medication guesses of 137 depressed patients and /or their doctors at the end of a 6-week r and omized trial of placebo , imipramine , and phenelzine . Overall , 78 % of the patients and 87 % of the doctors correctly distinguished between placebo and active medication . Clinical outcome , treatment condition , and their interaction each contributed to guessing accuracy , while medication experience and side effects assessed only in week 6 did not . Accuracy was high , however , even when cases were stratified for clinical outcome , indicating that other cues were available to the patients and doctors . These may include patterns and timing of side effects and clinical response not detectable in this end-point analysis Vitamin C has been a popular medication for preventing the common cold and reducing the severity of cold symptoms for many years . - ' Professor Pauling 's recent book on the subject has led to even further use of vitamin C in even larger doses . This study was performed to look for a difference in the frequency and severity of colds in a generally healthy , middle-class , medically aware population of employees at the National Institutes of Health . High doses of vitamin C were used for both prevention and treatment ; virus isolations were attempted in an effort to relate viral types to vitamin C response ; and the study was continued for a nine-month period in an attempt to examine seasonal variations of viruses and colds . The study was conducted so that nurses , physicians , and volunteers did not know who received placebo and who received ascorbic acid . Only the consulting statistician and the pharmacist could relate patient code numbers to medication received . Progress was monitored by a research committee not connected with the day-to-day activities Subjective and reinforcing effects of smoking a cigarette were examined within a 2 x 2 modified balanced-placebo design , which manipulated instructions about nicotine content ( i.e. , told regular nicotine vs. told low nicotine ) and actual nicotine dose ( given a regular nicotine br and vs. a denicotinized br and ) . Most ratings of the nicotine content and reward value of cigarettes were higher for those told regular nicotine versus told low nicotine , and for those given regular nicotine versus given low nicotine . Nicotine and instructions did not affect craving , withdrawal , or smoke-reinforced responding , but instructions affected the number of puffs earned for those given low nicotine ( i.e. , placebo effect ) . Thus , verbal information ( instructions ) can influence some responses to smoking consistent with the presence of placebo and antiplacebo effects The balanced placebo design ( BPD ) was used to evaluate the independent effects of nicotine dose and smoking-related expectancies on self-reported anxiety , urge to smoke , and withdrawal symptoms . After anxious mood was induced , participants smoked either a de-nicotinized cigarette or one with st and ard nicotine content . Nicotine dose was crossed with instructions that the cigarette was either de-nicotinized or st and ard . Nicotine cigarettes produced greater anxiety reduction than de-nicotinized cigarettes . Nicotine instructions attenuated anxiety only among those who held relevant expectancies . Nicotine dose and instructional set interacted such that either nicotine cigarettes or instructions that the cigarettes contained nicotine were sufficient to reduce urge to smoke . Implication s of these findings and method ological issues regarding use of the BPD with cigarettes are discussed BACKGROUND Information that enhances expectations about drug effectiveness improves the response to placebos for pain . Although asthma symptoms often improve with placebo , it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit . OBJECTIVE The study objective was to determine whether response to placebo or a leukotriene antagonist ( montelukast ) can be augmented by messages that increase expectation of benefit . METHODS A r and omized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups . Participants were r and omly assigned to one of 4 treatment groups in a factorial design ( ie , placebo with enhanced messages , placebo with neutral messages , montelukast with enhanced messages , or montelukast with neutral messages ) or to usual care . Assignment to study drug was double masked , assignment to message content was single masked , and usual care was not masked . The enhanced message aim ed to increase expectation of benefit from the drug . The primary outcome was mean change in daily peak flow over 4 weeks . Secondary outcomes included lung function and asthma symptom control . RESULTS Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo ; no differences were noted between the neutral placebo and usual care groups . Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants ; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference . Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect . CONCLUSIONS Optimistic drug presentation augments the placebo effect for patient-reported outcomes ( asthma control ) but not lung function . However , the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness |
552 | 30,152,074 | Results from the studies showed a high level of engagement .
Self-efficacy , psychological symptoms , and quality of life were the most commonly assessed psychosocial variables .
The present review showed that despite the heterogeneity in the studies assessed and inconsistent results , DI may constitute an excellent means to help cancer patients and survivors cope better with the disease and with treatment side effects , as they can improve self-management and wellbeing . | OBJECTIVE Digital health interventions ( DI ) open the possibility for cancer patients and survivors to manage the disease and its side effects when they return home after treatment .
This study aims to highlight the components of DI , investigate patient engagement with DI , and explore the effects of DI on psychosocial variables . | Background : Cancer patients experience many physical and psychosocial problems for which they need support . WebChoice is an Internet-based , interactive health communication application that allows cancer patients to monitor their symptoms and problems , provides individually tailored information and self-management support , e-communication with expert cancer nurses , and an e-forum for group discussion with other patients . Objective : The objective of this study was to examine the effects of WebChoice on symptom distress ( primary outcome ) , depression , self-efficacy , health-related quality of life , and social support ( secondary outcomes ) . Methods : In this 1-year repeated- measures r and omized controlled trial , 325 breast and prostate cancer patients were r and omized into 1 experimental group with access to WebChoice and 1 control group who received URLs of publicly available cancer Web sites . Results : Group differences on symptom distress were significant only for the global symptom distress index on the Memorial Symptom Assessment Scale ( slope estimate , −0.052 [ 95 % confidence interval , −0.101 to −0.004 ] ; t = 4.42 ; P = .037 ) . There were no significant group differences on secondary outcomes . Additional analyses showed significant within-group improvements in depression in the experimental group only . In the control group , self-efficacy and health-related quality of life deteriorated significantly over time . Conclusion : This r and omized controlled trial is one of the first to evaluate effects of an interactive health communication application to support cancer patients in illness management on symptoms . Although only 1 hypothesis was partially supported , the combined results show a clear trend toward better scores in the intervention group on most outcome measures . Implication s for Practice : If findings can be supported with additional research , WebChoice may become an important tool to support nursing care that can equip cancer patients to better manage their illness Abstract OBJECTIVE : Assess impact of a computer-based patient support system on quality of life in younger women with breast cancer , with particular emphasis on assisting the underserved . DESIGN : R and omized controlled trial conducted between 1995 and 1998 . SETTING : Five sites : two teaching hospitals ( Madison , Wis , and Chicago , Ill ) , two nonteaching hospitals ( Chicago , Ill ) , and a cancer re source center ( Indianapolis , Ind ) . The latter three sites treat many underserved patients . PARTICIPANTS : Newly diagnosed breast cancer patients ( N=246 ) under age 60 . INTERVENTIONS : Experimental group received Comprehensive Health Enhancement Support System ( CHESS ) , a home-based computer system providing information , decision-making , and emotional support . MEASUREMENTS AND MAIN RESULTS : Pretest and two posttest surveys ( at two- and five-month follow-up ) measured aspects of participation in care , social/information support , and quality of life . At two-month follow-up , the CHESS group was significantly more competent at seeking information , more comfortable participating in care , and had greater confidence in doctor(s ) . At five-month follow-up , the CHESS group had significantly better social support and also greater information competence . In addition , experimental assignment interacted with several indicators of medical underservice ( race , education , and lack of insurance ) , such that CHESS benefits were greater for the disadvantaged than the advantaged group . CONCLUSIONS : Computer-based patient support systems such as CHESS may benefit patients by providing information and social support , and increasing their participation in health care . These benefits may be largest for currently underserved population CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs Purpose Patients undergoing radiotherapy for prostate cancer suffer from a variety of symptoms which influence health-related quality of life . We have developed an application ( Interaktor ) for smartphones and tablets for early detection , reporting and management of symptoms , and concerns during treatment for prostate cancer . The study evaluates the effect on symptom burden and quality of life when using the application for real-time symptom assessment and management during radiotherapy for localized prostate cancer . Methods A non-r and omized controlled study was used at two university hospitals in Sweden where 64 patients constituted a control group and 66 patients made up an intervention group . The intervention group was asked to report symptoms via the application daily during the treatment as well as 3 weeks after . The EORTC QLQ-C30 and its module PR25 and the Sense of Coherence question naire were administered at three time points in both groups . Results The intervention group rated significantly lower levels of fatigue and nausea at the end of radiotherapy . Moreover , they had significantly less burden in emotional functioning , insomnia , and urinary-related symptoms at the end of treatment as well as 3 months later compared with the control group . In the multivariate analyses , with education and sense of coherence as covariates , the intervention group still significantly rated emotional functioning ( p = 0.007 ) , insomnia ( p = 0.017 ) , and urinary-related symptoms ( p = 0.008 ) as better than the control group at T2 . ConclusionS tudy findings suggest that Interaktor could be an efficient mHealth tool for facilitating supportive care needs during cancer treatment PURPOSE Early breast cancer survivors ( BCSs ) report high unmet care needs , and easily accessible care is not routinely available for this growing population . The Breast Cancer E-Health ( BREATH ) trial is a Web-based self-management intervention to support the psychological adjustment of women after primary treatment , by reducing distress and improving empowerment . PATIENTS AND METHODS This multicenter , r and omized , controlled , parallel-group trial evaluated whether care as usual ( CAU ) plus BREATH is superior to CAU alone . BREATH is delivered in sixteen fully automated weekly modules covering early survivorship issues . Two to 4 months post-treatment , BCSs were r and omly assigned to receive CAU + BREATH ( n = 70 ) or CAU alone ( n = 80 ) using a stratified block design ( ratio 1:1 ) . Primary outcomes were distress ( Symptom Checklist-90 ) and empowerment ( Cancer Empowerment Question naire ) , assessed before r and om assignment ( baseline , T0 ) and after 4 ( T1 ) , 6 ( T2 ) , and 10 months ( T3 ) of follow-up . Statistical ( analysis of covariance ) and clinical effects ( reliable change index ) were tested in an intention-to-treat analysis ( T0 to T1 ) . Follow-up effects ( T0 to T3 ) were assessed in assessment completers . RESULTS CAU + BREATH participants reported significantly less distress than CAU-alone participants ( -7.79 ; 95 % CI , -14.31 to -1.27 ; P = .02 ) with a small-to-medium effect size ( d = 0.33 ) , but empowerment was not affected ( -1.71 ; 95 % CI , 5.20 to -1.79 ; P = .34 ) . More CAU + BREATH participants ( 39 of 70 [ 56 % ] ; 95 % CI , 44.1 to 66.8 ) than CAU-alone participants ( 32 of 80 [ 40 % ] ; 95 % CI , 30.0 to 51.0 ) showed clinical ly significant improvement ( P = .03 ) . This clinical effect was most prominent in low-distress BCSs . Secondary outcomes confirmed primary outcomes . There were no between-group differences in primary outcomes during follow-up . CONCLUSION Access to BREATH reduced distress among BCSs , but this effect was not sustained during follow-up Background Physical activity ( PA ) behavior change interventions among cancer survivors have used face-to-face , telephone , email , and print-based methods . However , computer-tailored , Internet-delivered programs may be a more viable option to achieve PA behavior change . Objective The objective of this study is to test the feasibility and preliminary efficacy of a Web-based PA behavior change program among cancer survivors . Methods Nova Scotian cancer survivors ( N=415 ) who previously expressed interest in a research study were approached . Interested participants were asked to complete an online assessment of PA and quality of life ( QOL ) before being r and omized to either a theory-based PA behavior change program using the PA tracking website UWALK ( UCAN ; n=48 ) or usual care ( UC ; n=47 ) . After the intervention ( 9 weeks ) , participants completed another online assessment of PA and QOL as well as measures to evaluate the program and website . Descriptive analyses from surveys and Web analytic software were used to assess feasibility and mean change scores were used to test efficacy . Results Of all contacted survivors , 95 ( 22.3 % , 95/415 ) completed baseline measures and were r and omized with 84 ( 88 % , 84/95 ) completing the 9-week assessment . The behavior change program and website were rated highly on the satisfaction items . Average logins were 10.3 ( 1.1 per week ) and 26.0 % ( 111/432 ) of the weekly modules were completed . Most participants ( 71 % , 29/41 ) indicated they were more aware of their daily PA levels and 68 % ( 28/41 ) found the site easily navigable . Adjusted group differences in total exercise minutes favored the UCAN group by an increase of 42 minutes ( 95 % CI -65 to 150 ; P=.44 , d=0.17 ) . Results were more pronounced , though still nonsignificant , among those not meeting guidelines at baseline where UCAN increased PA by 52 minutes compared to a decrease of 15 minutes in UC ( adjusted between group difference=75 , 95 % CI -95 to 244 ; P=.38 , d=0.27 ) . Conclusions We found that Internet-delivery may be a feasible alternative to more costly methods to promote PA among Nova Scotian cancer survivors . Moreover , there was a trend toward increased PA among those in the UCAN group , especially among those who were not meeting PA guidelines at baseline . Future research should focus on recruiting inactive cancer survivors and engaging them in the website to determine the optimal potential of Web-based interventions for promoting PA in cancer survivors Background Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer . While oral chemotherapy includes benefits such as ease of administration , convenience , and minimization of invasive infusions , patients receive less oversight , support , and symptom monitoring from clinicians . Additionally , adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens . With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology , we created a mobile health intervention for medication and symptom management . Objective The objective of this study was to develop and evaluate the usability and acceptability of a smartphone app to support adherence to oral chemotherapy and symptom management in patients with cancer . Methods We used a 5-step development model to create a comprehensive mobile app with theoretically informed content . The research and technical development team worked together to develop and iteratively test the app . In addition to the research team , key stakeholders including patients and family members , oncology clinicians , health care representatives , and practice administrators contributed to the content refinement of the intervention . Patient and family members also participated in alpha and beta testing of the final prototype to assess usability and acceptability before we began the r and omized controlled trial . Results We incorporated app components based on the stakeholder feedback we received in focus groups and alpha and beta testing . App components included medication reminders , self-reporting of medication adherence and symptoms , an education library including nutritional information , Fitbit integration , social networking re sources , and individually tailored symptom management feedback . We are conducting a r and omized controlled trial to determine the effectiveness of the app in improving adherence to oral chemotherapy , quality of life , and burden of symptoms and side effects . At every stage in this trial , we are engaging stakeholders to solicit feedback on our progress and next steps . Conclusions To our knowledge , we are the first to describe the development of an app design ed for people taking oral chemotherapy . The app addresses many concerns with oral chemotherapy , such as medication adherence and symptom management . Soliciting feedback from stakeholders with broad perspectives and expertise ensured that the app was acceptable and potentially beneficial for patients , caregivers , and clinicians . In our development process , we instantiated 7 of the 8 best practice s proposed in a recent review of mobile health app development . Our process demonstrated the importance of effective communication between research groups and technical teams , as well as meticulous planning of technical specifications before development begins . Future efforts should consider incorporating other proven strategies in software , such as gamification , to bolster the impact of mobile health apps . Forthcoming results from our r and omized controlled trial will provide key data on the effectiveness of this app in improving medication adherence and symptom management . Trial Registration Clinical Trials.gov NCT02157519 ; https:// clinical trials.gov/ct2/show/NCT02157519 ( Archived by WebCite at http://www.webcitation.org/6prj3xfKA OBJECTIVE Many factors influence return to work ( RTW ) following cancer treatment . However specific factors affecting RTW across different cancer types are unclear . This study examined the role of clinical , sociodemographic , work and psychological factors in RTW following treatment for breast , gynaecological , head and neck , and urological cancer . METHODS A 12-month prospect i ve question naire study was conducted with 290 patients . Cox regression analyses were conducted to calculate hazard ratios ( HR ) for time to RTW . RESULTS Between 89 - 94 % of cancer survivors returned to work . Breast cancer survivors took the longest to return ( median 30 weeks ) , and urology cancer survivors returned the soonest ( median 5 weeks ) . Earlier return among breast cancer survivors was predicted by a greater sense of control over their cancer at work ( HR 1.2 ; 95 % CI : 1.09 - 1.37 ) and by full-time work ( HR 2.1 ; CI : 1.24 - 3.4 ) . Predictive of a longer return among gynaecological cancer survivors was a belief that cancer treatment may impair ability to work ( HR 0.75 ; CI : 0.62 - 0.91 ) . Among urological cancer survivors constipation was predictive of longer RTW ( HR 0.99 ; CI : 0.97 - 1.00 ) , whereas undertaking flexible working was predictive of returning sooner ( HR 1.70 ; CI : 1.07 - 2.7 ) . Head and neck cancer survivors who perceived greater negative consequences of their cancer took longer to return ( HR 0.27 ; CI : 0.11 - 0.68 ) . Those reporting better physical functioning returned sooner ( HR1.04 ; CI : 1.01 - 1.08 ) . CONCLUSION A different profile of predictive factors emerged for the four cancer types . In addition to optimal symptom management and workplace adaptations , the findings suggest that eliciting and challenging specific cancer and treatment-related perceptions may facilitate RTW OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review OBJECTIVES The psychosexual concerns of gynecologic cancer patients are often unaddressed and there are limited re sources available for women to deal with this highly sensitive topic . This feasibility study examines the participation rates and preliminary outcomes for an online support group design ed specifically for women who are sexually distressed subsequent to gynecologic cancer treatment METHODS A 12-week online intervention was developed to address the psychosexual impact of gynecologic cancer . This intervention included a professionally moderated , asynchronous discussion forum as well as the provision of psycho-educational material s addressing the psychosexual impact of gynecologic cancer . Each week , a new topic was introduced and relevant material was posted on the website . Women were encouraged to share their experiences related to the topic . Twenty-seven , sexually distressed , remitted gynecologic cancer patients were r and omly assigned to immediate treatment or a waitlist control condition . Participants completed question naires at baseline , 4-month and 8-month follow-ups assessing sexual distress as the primary outcome as well as anxiety , depression , and illness intrusiveness . RESULTS Participation rates differed between the two groups , with greater participation occurring in the second group . Exit interviews indicated that the majority of the participants were satisfied with the intervention . Intent-to-treat analyses suggest a small effect for reduction in sexual distress CONCLUSIONS This feasibility study suggests that women find this intervention acceptable . Further research is required to determine efficacy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose To investigate and compare the effects of mobile health ( mHealth ) and pedometer with conventional exercise program using a brochure on physical function and quality of life ( QOL ) . Methods The study was a prospect i ve , quasi-r and omized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled . All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise . The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises . Those in the conventional group received an exercise brochure . Physical measurements were conducted at baseline , 6 weeks , and 12 weeks . Self-reported physical activity ( international physical activity question naire-short form ) , general QOL ( European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 ) , and breast cancer-specific QOL ( Quality of Life Question naire Breast Cancer Module 23 ) were assessed at baseline and 12 weeks . A user satisfaction survey was assessed in the mHealth group . Results Basic characteristics were not different between the two groups except for age and previous radiotherapy . Physical function , physical activity , and QOL scores were significantly improved regardless of the intervention method , and changes were not significantly different between the two groups . Additionally , the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group . Conclusions Overall , both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function , physical activity , and QOL . This study provides a basis of mHealth research in breast cancer patients for progressing further developing field , although superiority of the mHealth over the conventional program was not definitely evident BACKGROUND And rogen treatment for prostate cancer can adversely affect functional domains of quality of life . We aim ed to assess quality of life in men with locally advanced prostate cancer in an open-label phase III r and omised comparison between lifelong endocrine treatment with and without radiotherapy . METHODS We obtained quality -of-life information from 872 ( 99 % ) of 875 eligible men with locally advanced prostate cancer ( T3 ; 78 % ) who were r and omly assigned , between 1996 and 2002 , to 3 months of total and rogen blockade followed by continuous endocrine treatment ( 439 patients ) or the same hormonal treatment with radiotherapy 3 months after r and omisation ( 436 patients ) . Prospect i ve outcomes included patient-reported symptoms and quality of life assessed with question naires from baseline to 4 years after r and omisation . Analysis was by intention to treat . This study is registered as an international st and ard r and omised controlled trial , number IS RCT N01534787 . FINDINGS 438 of 439 men assigned endocrine treatment and 434 of 436 assigned endocrine plus radiotherapy completed at least one question naire . Missing data at baseline and during follow-up was equally distributed between groups . At 4 years , 64 ( 18 % ) of 353 patients on combined therapy and 39 ( 12 % ) of 337 on endocrine-alone therapy had moderate to severe urinary bother ( p=0.005 ) , and 16 ( 4 % ) of 355 on combined therapy and five ( 2 % ) of 338 on endocrine treatment alone had pain while urinating ( p=0.024 ) . 37 ( 11 % ) of 350 in the combined group and 23 ( 7 % ) of 35 in the endocrine-only group had overall bother from all bowel symptoms ( p=0.022 ) . 281 ( 85 % ) of 332 in the combined-treatment group and 227 ( 72 % ) of 313 in the endocrine-only group had erectile dysfunction ( p=0.0002 ) . Quality of life at 4 years was similar , with the exception of decreased social function in patients receiving endocrine treatment plus radiotherapy . INTERPRETATION Although addition of radiotherapy to endocrine treatment significantly increased some treatment-related symptoms , none were serious . Given the substantial survival benefit of combined treatment , the increase of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with endocrine treatment alone Psychosocial pain management interventions are efficacious for cancer pain but are underutilized . Recent advances in mobile health ( mHealth ) technologies provide new opportunities to decrease barriers to access psychosocial pain management interventions . The objective of this study was to gain information about the accessibility and efficacy of mobile pain coping skills training ( mPCST ) intervention delivered to cancer patients with pain compared to traditional in-person pain coping skills training intervention . This study r and omly assigned participants ( N = 30 ) to receive either mobile health pain coping skills training intervention delivered via Skype or traditional pain coping skills training delivered face-to-face ( PCST-trad ) . This pilot trial suggests that mPCST is feasible , presents low burden to patients , may lead to high patient engagement , and appears to be acceptable to patients . Cancer patients with pain in the mPCST group reported decreases in pain severity and physical symptoms as well as increases in self-efficacy for pain management that were comparable to changes in the PCST-trad group ( p 's < 0.05 ) . These findings suggest that mPCST , which is a highly accessible intervention , may provide benefits similar to an in-person intervention and shows promise for being feasible , acceptable , and engaging to cancer patients with pain Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Women with breast carcinoma commonly experience psychologic distress following their diagnosis . Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives . Web‐based breast cancer social support groups are widely used , but little is known of their effectiveness . Preliminary evidence suggests that women benefit from their participation in web‐based support groups Background : Use of oral chemotherapy agents to treat cancer has increased . Patients are responsible for adhering to complex regimens while managing symptoms from adverse effects of the chemotherapy . Objective : This study examined an intervention to manage symptoms and adherence to oral agents . Methods : A 3-group pilot study determined how an Automated Voice Response ( AVR ) system alone ( n = 40 ) , or the AVR with strategies to manage symptoms and adherence ( n = 40 ) , or the AVR with strategies to manage adherence ( n = 39 ) reduced symptom severity and improved adherence . Participants received a Symptom Management Toolkit , completed a baseline interview , and were r and omized to receive 8 weekly AVR calls . An exit interview occurred at 10 weeks . Results : Mean age was 59.6 years , with 70 % female and 76 % white , and 42 % were nonadherent , with missed doses increasing with regimen complexity . Symptom severity declined over time in all groups . No difference was found in adherence rates , and higher adherence was related with lower symptom severity across groups . Conclusions : Adherence , a significant clinical problem , can affect efficacy of the cancer treatment . The AVR intervention alone was just as effective as the AVR plus the nurse intervention at promoting adherence and managing symptoms from adverse effects . Implication s for Practice : Nurses need to focus on patient education by ensuring patient underst and ing of oral agent regimen and the need to adhere to the oral agent for efficacious cancer treatment . Nurses can promote the use of medication reminders and self-management of symptoms from adverse effects , to support adherence to the oral agent Purpose This study evaluated the feasibility and preliminary efficacy of two 6-month , self-regulation interventions that focused on daily self-weighing ( DSW ) and used objective monitoring and tailored feedback about weight ( ±activity ) , to prevent weight gain among African American breast cancer survivors . Methods Participants ( n = 35 ) were r and omized to an intervention + activity monitoring ( INT+ ) , intervention ( INT ) , or control ( CON ) group . Interventions included a wireless scale ( ±activity tracker ) that transmitted objective data to a mobile app/website , emailed lessons , and tailored feedback based on objective weight ( ±activity data ) . Participants completed in-person and online assessment s at baseline , 3 months , and 6 months . Results Ninety-four percent of participants completed assessment s at 3 months , and 97 % at 6 months . Median ( IQR ) weight change after 6 months was −0.9 % ( −4.4–0.1 ) in the INT+ ( p = 0.075 ; p = 0.067 vs. CON ) and −0.2 % ( −4.2–1.3 ) in the INT groups ( p = 0.463 ; p = 0.357 vs. CON ) , versus a 0.2 % ( −0.7–1.7 ) gain in the CON group . The proportion of INT+ , INT , and CON participants that were at or below baseline weight was 72.7 , 53.8 , and 45.5 % , respectively ( effect sizes d = 0.64 , d = 0.18 ) . Most INT+ participants weighed and wore trackers ≥5 days/week ( INT+ , 81.9 % vs. INT , 38.5 % vs. CON , 0 % ; p < 0.0005 ; INT+ , 72.7 % ) . Both intervention groups perceived DSW as positive , and 100 % would recommend the program to other breast cancer survivors . Conclusion An intervention focused on DSW as a self-monitoring strategy shows promise for preventing weight gain in breast cancer survivors . Implication s for cancer survivorsDaily self-monitoring of weight and activity may be a feasible and accessible approach to promote weight gain prevention in breast cancer survivors . Clinical trial registration Clinical Trials.gov , Background The widespread and increasing use of oral anti-cancer medications has been ushered in by a rapidly increasing underst and ing of cancer pathophysiology . Furthermore , their popular ease of administration and potential cost savings has highlighted their central position in the health care system as a whole . These facts have heightened appreciation of the unique challenges associated with the use of oral anti-cancer medications ; especially in the long-term use of these medications and the associated side effects that may impede optimal adherence to their use . Therefore , we developed ChemOtheRapy Assistant , CORA , a personalized mobile phone – based self-management application to help cancer patients on oral anti-cancer medications . Objective Our objective is to evaluate the effect of CORA on adherence to oral anti-cancer medications and other clinical ly relevant outcomes in the management of patients with renal and prostate cancer . Methods The study will be implemented as a 2-parallel group r and omized controlled trial in 104 patients with renal or prostate cancer on oral anti-cancer medications over a 3-month study period . The intervention group will use CORA in addition to usual care for self-management while the control group will continue care as usual . Medication adherence will be measured objective ly by a Medication Event Monitoring System device and is defined as the percentage of prescribed doses taken . We will also assess the effect of the intervention on cancer-related symptoms measured by the MD And erson Symptom Inventory and unplanned hospital utilizations . Other outcomes that will be measured at study start , midpoint , and endpoint are health-related quality of life , cancer-related fatigue , and anxiety . Group differences in medication adherence will be examined by t tests or by non-parametric Mann-Whitney tests if the data are not normally distributed . Logistic regression will be used to identify potential predictors of adherence . Results We expect to have results for this study before the end of 2016 . Conclusions This novel mobile phone – enabled , multimodal self-management and educational intervention could lead to improvements in clinical outcomes and serve as a foundation for future mHealth research in improving outcomes for patients on oral anti-cancer medications PURPOSE / OBJECTIVES To determine proof of concept of a mobile health ( mHealth ) intervention delivering text messages ( texts ) to self-manage among patients prescribed oral anticancer agents ( OAs ) and to examine preliminary efficacy on symptoms and medication adherence . DESIGN A longitudinal r and omized , controlled trial . SETTING Two community cancer centers in the midwestern United States and a national specialty pharmacy . SAMPLE 80 adults with cancer who were newly prescribed OAs . METHODS Adherence and symptoms were assessed weekly for 10 weeks in both groups . The intervention group received daily texts for adherence and weekly for symptoms for 21 - 28 days , and satisfaction with the intervention was assessed . MAIN RESEARCH VARIABLES Medication adherence and symptom severity . FINDINGS Mean age was 58.5 years ( SD = 10.7 years ) , 48 participants were female , and 48 were Caucasian . Fewer symptoms were found in the intervention group with a moderate effect size . Adherence was higher in the text group using medical record and prescription data ( n = 26 ) with greater relative dose intensity of moderate to large effect size . Regarding acceptability , 57 % ( 83 of 145 ) of eligible participants consented , 39 of 40 participants completed the entire intervention , 30 participants read texts all of the time , and 34 participants were satisfied with the intervention . CONCLUSIONS Proof of concept and preliminary efficacy of an mHealth intervention using texts to promote self-management for patients prescribed OAs was demonstrated . Patients had high satisfaction with the texts , and adherence and symptoms improved after the intervention . IMPLICATION S FOR NURSING Texts show promise for patients with cancer who must manage their OAs . Additional research is needed prior to use in practice BACKGROUND Physical activity ( PA ) may be important for preventing chronic diseases for adolescent and young adult ( AYA ) childhood cancer survivors . R and omized controlled trials ( RCTs ) of PA interventions for AYA survivors are sparse , but necessary to determine effective programs for increasing PA among this population . Thus , we conducted a pilot RCT , testing the feasibility of a mobile health ( mHealth ) intervention to promote PA among AYA survivors . PROCEDURE We recruited 14- to 18-year-olds who were ≥1-year post cancer therapy from Seattle Children 's Hospital . The 10-week intervention consisted of a wearable PA-tracking device ( Fitbit Flex ) and a peer-based virtual support group ( Facebook group ) . Research staff helped set step goals and awarded badges weekly . Controls received usual care . Baseline assessment s occurred before r and omization and follow-up assessment s occurred during weeks 8 - 10 of the intervention period . Feasibility criteria are defined below . Qualitative interviews assessed acceptability . Exploratory outcomes included PA , quality of life , and motivation for PA . RESULTS All feasibility criteria were met : we recruited 60 survivors , intervention participants wore the Fitbit on the majority ( 71.5 % ) of intervention days , and ≥90 % of all participants completed question naires . Qualitative data confirmed intervention acceptability . Exploratory analyses found no significant adjusted group differences for change in moderate-to-vigorous PA ( 4.4 vs. 5.0 min/day ; P = 0.92 ) or sedentary time ( -4.5 vs. 1.0 min/day ; P = 0.73 ) , comparing intervention subjects to controls . Some modest differences were found for select subscales of quality of life and motivation for PA . CONCLUSIONS This mHealth PA intervention was feasible and acceptable to AYA childhood cancer survivors and warrants a fully powered RCT OBJECTIVES The information needs of cancer patients are highly variable . Literature suggests an improved ability to modulate personalised stress , increased patient involvement with decision making , greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information . The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer . MATERIAL S AND METHODS An application was developed for use with Apple iPad containing information on basic breast cancer biology , different treatments used and surgical techniques . Content and face validity studies were performed . A r and omized control trial was design ed , with a 1:2 allocation . Data collected include basic demographics and type of surgery . Question naires used included : the HADS , Mini-MAC , information technology familiarity and information satisfaction . RESULTS A total of 39 women participated . 13 women had access to an iPad containing additional information and 26 women acted as controls . The mean age was 54 and technology familiarity was similar among both groups . Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application ( p = 0.022 and 0.029 respectively ) . CONCLUSION Anxiety and depression in breast cancer patients is both multifactorial and significant , with anxiety levels directly correlating with reduced quality of life . Intuitively , information should improve anxiety levels , however , we have demonstrated that surgical patients with less information reported significantly lower anxiety . We advise the thorough testing and auditing of information initiatives before deployment Purpose The purpose of the study is to investigate the impact of differing delivery schedules of computer-tailored physical activity modules on engagement and physical activity behaviour change in a web-based intervention targeting breast cancer survivors . Methods Insufficiently active breast cancer survivors ( n = 492 ) were r and omly assigned to receive one of the following intervention schedules over 12 weeks : a three-module intervention delivered monthly , a three-module intervention delivered weekly or a single module intervention . Engagement with the website ( number of logins , time on site , modules viewed , action plans completed ) was measured using tracking software . Other outcomes ( website acceptability , physical activity behaviour ) were assessed using online surveys . Physical activity outcomes were analysed using regression models for both study completers and when applying intention-to-treat ( using multiple imputation ) . Results Completers allocated to the monthly module group rated the intervention higher ( b = 2.2 95 % CI = 0.02–4.53 ) on acceptability and had higher levels of resistance-training ( IRR = 1.88 , 95 % CI = 1.16–3.04 ) than those in the single module group . When accounting for missing data , these differences were no longer significant . The completion of at least two action plans was higher among those allocated to the monthly module group compared to those in the weekly module group ( 53 vs 40 % , p = 0.02 ) ; though the completion of at least two modules was higher in the weekly module group compared to the monthly module group ( 60 vs 46 % ; p = 0.01 ) . There were no other significant between group differences observed . Conclusion This study provides preliminary evidence that web-based computer-tailored interventions can be used to increase physical activity among breast cancer survivors . Further , there were some outcome differences based on how the tailored modules were delivered , with the most favourable outcomes observed in the monthly delivery group . Implication s for Cancer SurvivorsThis study will be useful for informing the design of future web-based interventions targeting breast cancer survivors OBJECTIVE This study examined the feasibility and acceptability of an Individual Internet Intervention ( III ) embedded and integrated into an Internet Support Group ( ISG ) with the ultimate goal of enhancing adherence and learning , compared with an individual internet invention alone . METHOD Thirty-one posttreatment cancer survivors were r and omized in groups of seven to nine to either the 8-week III + ISG intervention or the 8-week III condition . Seventeen participants met the Hospital Anxiety and Depression Scale ( HADS ) criteria for depressive symptoms ( HADS ≥ 8) . RESULTS Among all participants , the mean number of logins over 8 weeks was 20.8 ± 17.7 logins for the III + ISG compared with 12.5 ± 12.5 in III-only ( p = 0.15 ) . Two participants in the III + ISG dropped out , compared with five in III ( p = 0.39 ) . Among the 17 participants with depressive symptoms at baseline , both the Onward and the III-only condition showed large reductions in the depression scale of HADS ( d = 1.27 and 0.89 , respectively ) . Improvement over time and time x treatment effects only reached trend significance levels ( ps = 0.07 & 0.12 ) as this pilot was not powered to detect these differences . CONCLUSION Both the III + ISG and III-only demonstrated pre-post reductions in depressive symptoms and high rates of utilization compared with other web-based treatments for depression . Although it is premature to make any determination as to the efficacy of the interventions tested in this feasibility study , these results indicate that pursuing the III + ISG model , as well as st and ard IIIs , may be fruitful areas of future research INTRODUCTION Text messaging ( TMs ) on cell phones is emerging as an effective means of delivering behavioral interventions . However , little is known about TM use in adult cancer patients . The present study aim ed to extend knowledge on acceptability of a TM intervention in adult cancer patients ; examine factors of those screened and enrolled ; and compare recruitment at a large national specialty pharmacy versus community-based cancer clinics . MATERIAL S AND METHODS Screening , enrollment , and baseline data collected in two r and omized controlled trials examining the efficacy of TMs on medication adherence or symptom severity in adults prescribed oral anticancer agents were linked . Chi-square , Fisher 's exact , t-tests , and generalized linear modeling were used to examine sociodemographics , cancer type and stage , depressive symptoms , self-efficacy , social support , and symptoms . RESULTS The cancer clinics screened 293 patients , 43 % were eligible , and 56 % consented . The specialty pharmacy screened 169 patients , 72 % were eligible , and 74 % consented . Mean age was 58 years and did not differ by recruitment setting . Later stage disease ( p = 0.01 ) and higher number of symptoms ( p < 0.01 ) , and symptom severity ( p = 0.02 ) and interference ( p = 0.01 ) were observed among patients recruited at the specialty pharmacy . No group differences were found for depression , physical function , cognition , self-efficacy , or social support . DISCUSSION Adult cancer patients were likely to participate in a TM intervention trial . Recruiting through the specialty pharmacy reached a population with higher cell phone ownership and TM usage ; with greater interest in a TM intervention compared to the cancer clinics INTRODUCTION This multisite , r and omized controlled trial assigned 75 adult cancer patients prescribed an oral anticancer agent to either an experimental group that received daily text messages for adherence for 21 days plus usual care or a control group that received usual care . MATERIAL S AND METHODS Measures were administered at baseline , weekly ( Weeks 1 - 8 ) , and at exit ( Week 9 ) . A satisfaction survey was conducted following the intervention . Acceptability , feasibility , and satisfaction were examined . Primary outcomes were adherence and symptoms . Secondary outcomes were depressive symptoms , self-efficacy , cognition , physical function , and social support . Mixed or general linear models were used for the analyses comparing trial groups . Effect sizes ( ES ) were estimated to gauge clinical significance . RESULTS Regarding acceptability , 57.2 % ( 83 of 145 ) of eligible patients consented , 88 % ( n = 37 of 42 ) receiving text messages read them most or all of the time , and 90 % ( n = 38 ) were satisfied . The differences between experimental and control groups ' ES were 0.29 for adherence , 0.21 for symptom severity , and 0.21 for symptom interference , and differences were not statistically significant . Furthermore , perceived social support was higher ( p = 0.04 ; ES = 0.54 ) in the experimental group . CONCLUSIONS Proof of concept and preliminary efficacy of a mobile health intervention using text messages to promote adherence for patients prescribed oral anticancer agents were demonstrated . Patients accepted and had high satisfaction with the intervention , and adherence improved after the intervention . Text messages show promise . Additional research is needed prior to use in practice BACKGROUND Over 12,000 children are diagnosed with cancer every year in the United States . In addition to symptoms associated with their disease , children undergoing chemotherapy frequently experience significant pain , which is unfortunately often undertreated . The field of m-Health offers an innovative avenue for pain assessment and intervention in the home setting . The current study describes the development and initial evaluation of a tablet-based program , Pain Buddy , aim ed to enhance pain management and foster improved quality of life in children ages 8 - 18 years undergoing cancer treatment . METHODS An animated avatar-based tablet application was developed using state-of-the-art software . Key aspects of Pain Buddy include daily pain and symptom diaries completed by children , remote monitoring of symptoms by uploading patient 's data through internet to a cloud server , cognitive and behavioral skills training , interactive three-dimensional avatars that guide children through the program , and an incentive system to motivate engagement . Twelve children between the ages of 8 and 18 participated in a pilot study of Pain Buddy . RESULTS Children were highly satisfied with the program . Pain and appetite disturbances were most frequently endorsed . Symptom trigger alerts to outside providers were largely related to clinical ly significant pain . Children infrequently used analgesics , and reported using some non-pharmacological pain management strategies . CONCLUSION Pain Buddy appears to be a promising tool to improve pain and symptom management in children undergoing cancer treatment . Results from the current study will inform future improvements to Pain Buddy , in preparation for a r and omized controlled trial to assess the efficacy of this innovative treatment |
553 | 30,682,131 | Conclusions Evidence of moderate quality indicates that training popular opinion leaders is effective in reducing avoidance intent and prejudicial attitude and improving compliance to universal pre caution .
Very low quality evidence indicates that professionally-assisted peer group interventions , modular interactive training , participatory self-guided assessment and intervention , contact strategy combined with information giving and empowerment are effective in reducing HIV-related stigma . | Introduction Stigma and discrimination ( SAD ) related to HIV compromise access and adherence to treatment and support programs among people living with HIV ( PLHIV ) .
The ambitious goal of ending the epidemic of HIV by 2030 set by the United Nations Joint Program of HIV/AIDS ( UNAIDS ) will thus only be achieved if HIV-related stigma and discrimination are reduced . | Introduction Globally , HIV-related stigma is prevalent in healthcare setting s and is a major barrier to HIV prevention and treatment adherence . Some intervention studies have showed encouraging outcomes , but a gap continues to exist between what is known and what is actually delivered in medical setting s to reduce HIV-related stigma . Methods This article describes the process of implementing a stigma reduction intervention trial that involved 1760 service providers in 40 hospitals in China . Guided by Diffusion of Innovation theory , the intervention identified and trained about 15–20 % providers as popular opinion leaders ( POLs ) to disseminate stigma reduction messages in each intervention hospital . The intervention also engaged governmental support in the provision of universal pre caution supplies to all participating hospitals in the trial . The frequency of message diffusion and reception , perceived improvement in universal pre caution practice s and reduction in the level of stigma in hospitals were measured at 6- and 12-month follow-up assessment s. Results Within the intervention hospitals , POL providers reported more frequent discussion s with their co-workers regarding universal pre caution principles , equal treatment of patients , provider-patient relationships and reducing HIV-related stigma . Service providers in the intervention hospitals reported more desirable intervention outcomes than providers in the control hospitals . Our evaluation revealed that the POL model is compatible with the target population , and that the unique intervention entry point of enhancing universal pre caution and occupational safety was the key to improved acceptance by service providers . The involvement of health authorities in supporting occupational safety was an important element for sustainability . Conclusions This report focuses on explaining the elements of our intervention rather than its outcomes . Lessons learned from the intervention implementation will enrich the development of future programs that integrate this or other intervention models into routine medical practice , with the aim of reducing HIV-related stigma and improving HIV testing , treatment and care in medical setting People living with HIV ( PLWH ) experience greater psychological distress than the general population . Evidence from high-incomes countries suggests that psychological interventions for PLWH can improve mental health symptoms , quality of life , and HIV care engagement . However , little is known about the effectiveness of mental health interventions for PLWH in low- and middle-income countries ( LMICs ) , where the large majority of PLWH reside . This systematized review aims to synthesize findings from mental health intervention trials with PLWH in LMICs to inform the delivery of mental health services in these setting s. A systematic search strategy was undertaken to identify peer- review ed published papers of intervention trials addressing negative psychological states or disorders ( e.g. depression , anxiety ) among PLWH in LMIC setting s. Search results were assessed against pre-established inclusion and exclusion criteria . Data from papers meeting criteria were extracted for synthesis . Twenty-six papers , published between 2000 and 2014 , describing 22 unique interventions were identified . Trials were implemented in sub-Saharan Africa ( n = 13 ) , Asia ( n = 7 ) , and the Middle East ( n = 2 ) , and addressed mental health using a variety of approaches , including cognitive-behavioral ( n = 18 ) , family-level ( n = 2 ) , and pharmacological ( n = 2 ) treatments . Four r and omized controlled trials reported significant intervention effects in mental health outcomes , and 11 preliminary studies demonstrated promising findings . Among the limited mental health intervention trials with PLWH in LMICs , few demonstrated efficacy . Mental health interventions for PLWH in LMICs must be further developed and adapted for re source -limited setting s to improve effectiveness This study assessed the effect of a brief intervention aim ed at reducing HIV-related stigma among service providers in China . From December 2005 to June 2006 , 138 service providers from four county hospitals in the Yunnan province of China were r and omly assigned into either an intervention or a control condition . HIV stigma reduction concepts were conveyed through participatory small group activities , including role-plays , games , group discussion s , and testimony by an HIV advocate . Participants were assessed at baseline before the intervention , and at 3- and 6-month follow-ups . Data were analyzed using a logistic regression mixed-effects model . Service providers in the brief intervention condition were significantly more likely to report better protection of patients ' confidentiality and right to HIV testing , lower levels of negative feelings toward people living with HIV/AIDS , and more accurate underst and ing and practice of universal pre caution s. This brief intervention pilot showed potential in reducing HIV stigma and discrimination among service providers in China . Further intervention trials are needed to test the efficacy and long-term outcomes of this intervention HIV infection is increasingly prevalent in adolescents , and primary prevention programmes have been most effective when based on existing theories , including social cognitive theory ( SCT ) . Nurses play an important role in assessing adolescents ' risk for HIV infection and in recommending preventive behaviour change , if their comfort with these activities is increased . Practising nurses ( n = 88 , mean age = 40.8 ) from a university medical centre and surrounding hospitals participated in either a didactic or SCT-based workshop and a vignette-based assessment . Utilizing a r and omized controlled design , this study compared the effectiveness of the two types of workshops by measuring HIV-related knowledge and attitudes , as well as comfort with and intent to perform HIV-related risk assessment s. Differences in comfort and intent based on target patients ' cultural descriptors were also evaluated . The SCT-based workshops yielded more positive results for all four outcome variables at the 8-week follow-up ( F2,71 = 4.27 , P < 0.02 ) . Cultural stereotyping also appeared to play a role in nurses ' intent to perform assessment s ( F2,74 = 11.81 , P < 0.001 ) . Suggestions for improving the workshops and incorporating other theory-based approaches are discussed BACKGROUND The st and ardized patient approach has proved to be an effective training tool for medical educators . This article explains the process of employing st and ardized patients in an HIV stigma reduction intervention in healthcare setting s in China . METHODS The study was conducted in 40 hospitals in two provinces of China . One year after the stigma reduction intervention , st and ardized patients made unannounced visits to participating hospitals , r and omly approached service providers on duty and presented symptoms related to HIV and disclosed HIV-positive test results . After each visit , the st and ardized patients evaluated their providers ' attitudes and behaviours using a structured checklist . St and ardized patients also took open-ended observation notes about their experience and the evaluation process . RESULTS Seven st and ardized patients conducted a total of 217 assessment s ( 108 from 20 hospitals in the intervention condition ; 109 from 20 hospitals in the control condition ) . Based on a comparative analysis , the intervention hospitals received a better rating than the control hospitals in terms of general impression and universal pre caution compliance as well as a lower score on stigmatizing attitudes and behaviours toward the st and ardized patients . CONCLUSION St and ardized patients are a useful supplement to traditional self-report assessment s , particularly for measuring intervention outcomes that are sensitive or prone to social desirability The aim of the study was to improve health workers ' skills and confidence in dealing with patients with HIV disease and increase attention to patients ' human rights . A longitudinal controlled trial was carried out in which one Nigerian state served as the intervention site and the adjacent state served as the control site for an intervention and dissemination of training in clinical management , health education , and attitudinal change toward patients with HIV disease . The intervention group n=1072 , control group n=480 . Following initial question naire-defining focus groups , nurses , laboratory technologists and physicians in all base hospitals in the intervention state were trained by influential role models who attended the initial training . Data were collected in all sites pre-training and 1 y later . Hierarchical multiple regression analysis controlling for baseline data , and orthogonal factor analysis to define scales were used . Data showed significant positive changes after 1 y in the intervention group on perception of population risk assessment , attitudes and beliefs about people with HIV disease , less fear and more sympathy for and responsibility toward HIV patients , and an increase in self-perceived clinical skills . There was increased willingness to treat and teach colleagues about people with HIV . Clinician fear and discrimination were significantly reduced , and the climate of fear that was associated with HIV was replaced with a professional concern . There was increased underst and ing of appropriate psychosocial , clinical and human rights issues associated with HIV treatment and prevention . This intervention , targeting health workers in an entire state and using HIV/AIDS information , role modeling , diffusion of training and discussion s of discrimination and human rights , significantly affected the perception of risk groups and behaviors , perceived skills in treatment and counseling , reduced fears and increased concern for people with HIV disease , and improved the climate of treatment and prevention of HIV disease compared with a control state & NA ; We tested the impacts of a professionally assisted peer‐group intervention on Chilean health workers ' HIV‐related knowledge , attitudes , and behaviors using a quasi‐experimental design with a pretest and 3‐month posttest . Two Santiago suburbs were r and omly assigned to the intervention or delayed intervention control condition . Five community clinics per suburb participated . Interested workers at the intervention ( n = 262 ) and control ( n = 293 ) clinics participated and completed both evaluations . At posttest , intervention clinic workers had higher knowledge and more positive attitudes regarding HIV , condoms , stigmatization , and self‐efficacy for prevention . They reported more partner discussion about safer sex , less unprotected sex , and more involvement in HIV prevention activities in the clinic and the community , but they did not report fewer sexual partners or more st and ard pre caution s behaviors . Because of these positive impacts , the program will become a regular continuing education unit that can be used to meet health‐worker licensing requirements Objective To evaluate an AIDS education intervention for health workers in Metro Manila hospitals . Methods A r and omized controlled education program consisting of lectures , role-plays , posters and pamphlets was delivered to physicians , nurses , laboratory technologists and orderlies in Manila hospitals . Knowledge , attitudes and infection control practice s were measured before , immediately after , and 2 months after the intervention . Results Baseline survey among 641 hospital workers revealed poor knowledge , negative attitudes towards AIDS patients , and inappropriate infection control practice s. Immediately after the intervention , there was significant improvement in ( 1 ) knowledge scores ( 8.7–11.2 in the intervention group versus 8.5–9.5 in the control group ; range , 0–14 ) , ( 2 ) attitude scores ( 54.4–60.6 versus 54.6–56.8 ; range , 22–88 ) , and ( 3 ) needle-recapping practice s ( 14–43 % versus 39–43 % ) ( all P values < 0.001 ) . After 2 months , attitude scores in the experimental group fell to the same level as those of the control group , while improvements in knowledge and needle recapping were largely maintained . Role-playing was considered by the participants to be the most effective component of the intervention . Conclusions These results suggest that AIDS training for hospital workers in the Philippines and in similar countries is necessary and can be effective . Ideally , such training should include role-playing and should be ongoing in order to sustain the effect OBJECTIVES The objective of the intervention was to reduce service providers ' stigmatizing attitudes and behaviors toward people living with HIV . METHODS The r and omized controlled trial was conducted in 40 county-level hospitals in 2 provinces of China between October 2008 and February 2010 . Forty-four service providers were r and omly selected from each hospital , yielding a total of 1760 study participants . We r and omized the hospitals to either an intervention condition or a control condition . In the intervention hospitals , about 15 % of the popular opinion leaders were identified and trained to disseminate stigma reduction messages . RESULTS We observed significant improvements for the intervention group in reducing prejudicial attitudes ( P < .001 ) , reducing avoidance intent towards people living with HIV ( P < .001 ) , and increasing institutional support in the hospitals ( P = .003 ) at 6 months after controlling for service providers ' background factors and clinic-level characteristics . The intervention effects were sustained and strengthened at 12 months . CONCLUSIONS The intervention reduced stigmatizing attitudes and behaviors among service providers . It has the potential to be integrated into the health care systems in China and other countries In response to a Department of Health , Engl and , circular encouraging policies of named voluntary antenatal HIV antibody testing , one West Midl and s health authority in Engl and introduced a policy of raising the issue proactively at the first antenatal attendance . In order to facilitate this policy a short staff education programme was provided for midwives . This paper reports on part of a study which aim ed to evaluate the impact of the HIV awareness training programme . A sample of midwives ( n = 65 ) was r and omly selected for inclusion in the study . Thirty-three had attended training and 32 had not . Data were collected using a self-administered question naire exploring knowledge of aetiology of HIV/AIDS , knowledge of transmission , knowledge of obstetric and paediatric HIV , attitudes to HIV , issues related to antenatal HIV antibody testing and opinions about the HIV awareness training programme . Results indicated no significant difference in levels of knowledge or in attitude between those who had attended the training programme and those who had not . Similarly , no significant difference was found in terms of how midwives would react to women requesting HIV antibody testing . Many of the results contradict the current literature and as a conclusion it is suggested that there is a need to review HIV-related training for midwives This study compared the effectiveness of an AIDS knowledge-only program ( knowledge ) with a combined program of AIDS knowledge and contact with people having HIV/AIDS ( PHA ) ( knowledge-contact ) in reducing nursing students ' stigma and discrimination towards PHA and in enhancing their emotional competence to serve PHA . Eighty-nine nursing students from two universities in Hong Kong were r and omly assigned to either the knowledge or the knowledge-contact condition . All participants completed measures of AIDS knowledge , stigmatizing attitudes , fear of contagion , willingness to treat , positive affect , and negative affect at pre-test , post-test , and six-week follow-up . Findings showed that in both groups , significant improvement in AIDS knowledge , stigmatizing attitudes , fear of contagion , willingness to treat , and negative affect were found at post-test . The effects on AIDS knowledge , fear of contagion , willingness to treat , and negative affect were sustained at follow-up for both groups . Intergroup comparisons at post-test showed that the effectiveness of knowledge-contact program was significantly greater than knowledge program in improving stigmatizing attitudes . No significant difference between the two groups was found at follow-up . Findings showed the short-term effect of contact in improving nursing students ' attitudes and emotional competence in serving PHA . Implication s for research and training of nursing staff were discussed ABSTRACT Previous studies suggest that the implementation of universal pre caution ( UP ) plays a role in reducing HIV stigma . In this study we investigate the efficacy of a stigma reduction intervention on UP compliance and explore whether UP compliance could potentially influence HIV stigma reduction in medical setting s. A r and omized controlled intervention trial was conducted in two provinces of China with 1760 healthcare service providers recruited from 40 county-level hospitals . Longitudinal analyses included data collection at baseline , 6- , and 12-month follow-up assessment s. Using a hierarchical modeling approach , we estimated the intervention effect for each provider 's UP compliance and its potential mediating role on HIV stigma with the bootstrapping method . A significant intervention effect on UP compliance was observed at both the 6- and 12-month follow-up assessment s. The intervention effect on provider avoidance intent was partially mediated by the provider 's own UP compliance at the two follow-up points . This study provides evidence that UP compliance should be part of HIV stigma reduction programs , especially in re source -restrained countries . Findings suggest that a protected work environment may be necessary but not sufficient to address HIV stigma in medical setting HIV stigma can be devastating and is common among health care providers , particularly nurses . The objectives of this study were to ( a ) assess the acceptability and feasibility of a brief stigma-reduction curriculum among a convenience sample of Indian nursing students and ( b ) examine the preliminary effect of this curriculum on their knowledge , attitudes , and intent to discriminate . At baseline , 57 % of students had at least one misconception about HIV transmission , 38 % blamed people living with HIV for their infection , and 87 % and 95 % demonstrated intent to discriminate while dispensing medications and drawing blood , respectively . Following the curriculum , HIV-related knowledge increased while blame , endorsement of coercive policies , and intent to discriminate decreased significantly . In addition , more than 95 % of participants described the curriculum as practice changing . This brief intervention result ed in decreased stigma levels and was also highly acceptable to the nursing students . Next steps include rigorous evaluation in a r and omized controlled trial Purpose A r and omized controlled trial with a matched design was conducted during October 2008 and February 2010 , aim ing at reducing HIV-related stigma in healthcare setting s. Methods Forty county hospitals in Fujian and Yunnan provinces of China were matched into pairs and r and omized to either an intervention condition or a control condition . Forty-four service providers were r and omly selected from each hospital , yielding a sample of 1,760 . Intervention outcomes were assessed at baseline , 6 and 12 months based on venue-based pair comparisons . We identified and trained 30 popular opinion leaders in each intervention hospital among service providers to disseminate stigma-reduction messages to their peer providers . Results Hospital and participant characteristics were comparable between the intervention and control conditions . Thirteen out of twenty pairs of hospitals showed significant reduction in the stigma outcome measure at the 6-month follow-up assessment . For most hospitals , the intervention effects were maintained at the 12-month follow-up assessment . Among the 13 pair of hospitals , which showed intervention effects at 6 months , eight were in Fujian and five were in Yunnan . The non-significant hospitals at 6 months had more beds than significant hospitals . However , the difference did not reach statistical significance . Conclusions A matched design and venue-based analysis provide more insight in assessing intervention effects for facility-based intervention trials . The identification of venue-based or hospital characteristics that are associated with intervention efficacy provides additional implication s for the adaptation and implementation of future interventions |
554 | 31,608,141 | Conclusions : Despite the lack of long-term follow-up and heterogeneity of the available evidence , prostate SBRT affords appropriate biochemical control with few high- grade toxicities . | Background : Despite the increasing worldwide utilization of stereotactic body radiation therapy ( SBRT ) for prostate cancer , there are no known summative data regarding its safety and efficacy .
To address this knowledge gap , we conducted a PRISMA -guided systematic review and meta- analysis of prospect i ve prostate SBRT trials . | Background Quality of life ( QoL ) is one of the most significant issues in prostate cancer treatment decisions . This study aim ed to investigate the toxicity of hypofractionated stereotactic radiotherapy ( SBRT ) and QoL after treatment in localized prostate cancer patients . Material s and methods A prospect i ve single-center clinical study was performed in low- and intermediate-risk prostate cancer patients . Patients received 33.5 Gy in 5 fractions ( SHARP regimen ) . Acute and late toxicity was assessed according to RTOG/EORTC score . Patients filled out EORTC QLQ-C30 and prostate cancer-specific QLQ-PR25 question naires . Results The analysis included 68 prostate cancer patients ( 55–83 years , median 73 ) with clinical stage T1c-T2cN0M0 , median combined Gleason score of 6 ( 3–8 ) , and median prostate-specific antigen ( PSA ) level of 10 ng/mL ( 4–20 ng/mL ) . Neoadjuvant and rogen deprivation therapy was given to 52 patients ( 76.5 % ) , and stopped in 31 patients ( 45.5 % ) after 6 months ; in 21 patients ( 31 % ) after 2–3 years . Average and median follow-up was 24 months ( 18–45 ) . Median nadir PSA level was 0.03 ng/mL for all patients and 0.6 ng/mL for patients without hormone treatment . No patients had PSA failure . There were no acute grade IV toxicities . One patient ( 1.5 % ) developed grade III and 24 patients ( 35.3 % ) grade II acute bladder toxicity . No one developed grade III and 7 patients ( 10.3 % ) grade II acute rectal toxicity . No grade III or IV late gastrointestinal or genitourinary toxicities were reported . Grade II late urinary symptoms were observed in 8 patients ( 11.8 % ) and gastrointestinal symptoms in 3 patients ( 4.4 % ) . Global health status/QoL was good and improved during the observational period . ConclusionS BRT for prostate cancer patients is a well-tolerated treatment in terms of toxicity and QoL , has no negative impact on functioning and everyday life , with the important benefit of a short treatment period . However , long-term follow-up data are needed . ZusammenfassungHintergrundDie Lebensqualität ( QoL ) ist zu einem der wichtigsten Schwerpunkte bei der Wahl der Prostatakarzinombeh and lung geworden . Das Thema dieser Studie war die Untersuchung der Toxizität der hypofraktionierten stereotaktischen Radiotherapie ( SBRT ) und der QoL nach Beh and lung des lokal begrenzten Prostatakarzinoms . Material ien und Method enDie prospektive , monozentrische , klinische Studie wurde bei Prostatakarzinompatienten mit niedrigem bis mittlerem Risiko durchgeführt . Die Patienten erhielten 33,5 Gy in 5 Fraktionen ( SHARP-Beh and lungsschema ) . Akute und späte Toxizität wurden nach den Kriterien des RTOG/EORTC-Scores klassifiziert . Die Patienten füllten das EORTC-QLQ-C30- und das prostatakarzinomspezifische QLQ-PR25-Formular aus . ErgebnisseDie Analyse umfasste 68 Prostatakarzinompatienten ( medianes Alter 73 , Spanne 55–83 Jahre ) i m klinischen Staging T1c – T2cN0M0 , mit einem medianen Gleason-Score von 6 ( Spanne 3–8 ) und einem medianen PSA-Wert ( prostataspezifisches Antigen ) von 10 ng/ml ( Spanne 4–20 ng/ml ) . Eine neoadjuvante And rogendeprivationstherapie erhielten 52 Patienten ( 76,5 % ) ; die Hormontherapie beendet 31 Patienten ( 45,5 % ) nach 6 Monaten und 21 Patienten ( 31 % ) nach 2–3 Jahren . Das durchschnittliche und mediane Follow-up dauerte 24 Monate ( Spanne 18–45 ) . Der mediane PSA-Nadir betrug 0,03 ng/ml für alle Patienten und 0,6 ng/ml für Patienten ohne Hormontherapie . PSA-Versagen und akute Grad-IV-Toxizitäten traten nicht auf . Ein Patient ( 1,5 % ) hatte eine Grad-III- und 24 Patienten ( 35,3 % ) eine Grad-II-Harnblasentoxizität , kein Patient eine Grad-III- und 7 Patienten ( 10,3 % ) eine akute Grad-II-Rektumtoxizität . Späte gastrointestinale oder urogenitale Toxizitäten III . oder IV . Grade s wurden nicht berichtet . Bei 8 Patienten ( 11,8 % ) traten späte Miktionsbeschwerden II . Grade s und bei 3 Patienten ( 4,4 % ) gastrointestinale Symptome auf . Globaler Gesundheitsstatus/QoL war gut und besserte sich in der untersuchten Zeit . SchlussfolgerungSBRT ist beim Prostatakarzinom eine gut tolerierte Beh and lung hinsichtlich Toxizität und QoL , ohne negativen Einfluss auf das Alltagsleben und dem wichtigen Vorteil einer kurzen Beh and lungszeit . Langfristige Follow-up-Untersuchungen müssen noch folgen PURPOSE To report the short-term clinical outcomes and acute and late treatment-related genitourinary ( GU ) and gastrointestinal ( GI ) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy ( SBRT ) . METHODS AND MATERIAL S Between 2011 and 2014 , 24 patients with prostate cancer were treated with SBRT to the prostate gl and and proximal seminal vesicles . A high-dose avoidance zone ( HDAZ ) was created by a 3-mm expansion around the rectum , urethra , and bladder . Patients were treated to a minimum dose of 36.25 Gy in 5 fractions , with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ . Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale , version 4 . RESULTS The median follow-up was 25 months ( range , 18 - 45 months ) . Nine patients ( 38 % ) experienced an acute grade 2 GU toxicity , which was medically managed , and no patients experienced an acute grade 2 GI toxicity . Two patients ( 8 % ) experienced late grade 2 GU toxicity , and 2 patients ( 8 % ) experienced late grade 2 GI toxicity . No acute or late grade ≥3 GU or GI toxicities were observed . The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8 % ( 95 % confidence interval 75.6%-99.4 % ) , and both biochemical failures occurred in patients with high-risk disease . All patients are currently alive at the time of this analysis and continue to be followed . CONCLUSIONS A heterogeneous prostate SBRT planning technique with differential treatment volumes ( low dose : 36.25 Gy ; and high dose : 50 Gy ) with an HDAZ provides a safe method of dose escalation . Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N97182923 . Findings Between Oct 18 , 2002 , and June 17 , 2011 , 3216 men were enrolled from 71 centres and r and omly assigned ( 74 Gy group , 1065 patients ; 60 Gy group , 1074 patients ; 57 Gy group , 1077 patients ) . Median follow-up was 62·4 months ( IQR 53·9–77·0 ) . The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3 % ( 95 % CI 86·0–90·2 ) in the 74 Gy group , 90·6 % ( 88·5–92·3 ) in the 60 Gy group , and 85·9 % ( 83·4–88·0 ) in the 57 Gy group . 60 Gy was non-inferior to 74 Gy ( HR 0·84 [ 90 % CI 0·68–1·03 ] , pNI=0·0018 ) but non-inferiority could not be cl aim ed for 57 Gy compared with 74 Gy ( HR 1·20 [ 0·99–1·46 ] , pNI=0·48 ) . Long-term side-effects were similar in the hypofractionated groups compared with the conventional group . There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures . The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group ( RTOG ) grade 2 or worse bowel and bladder adverse events was 13·7 % ( 111 events ) and 9·1 % ( 66 events ) in the 74 Gy group , 11·9 % ( 105 events ) and 11·7 % ( 88 events ) in the 60 Gy group , 11·3 % ( 95 events ) and 6·6 % ( 57 events ) in the 57 Gy group , respectively . No treatment-related deaths were reported . Interpretation Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new st and ard of care for external-beam radiotherapy of localised prostate cancer . Funding Cancer Research UK , Department of Health , and the National Institute for Health Research Cancer Research Network BACKGROUND Studies have reported a low α/β ratio for prostate cancer , suggesting that hypofractionation could enhance the biological tumour dose without increasing genitourinary and gastrointestinal toxicity . In the multicentre phase 3 , HYpofractionated irradiation for PROstate cancer ( HYPRO ) trial , hypofractionated radiotherapy was compared with conventionally fractionated radiotherapy for treatment of prostate cancer . We have previously reported acute and late incidence of genitourinary and gastrointestinal toxicity ; here we report protocol -defined 5-year relapse-free survival outcomes . METHODS We did an open-label , r and omised , phase 3 trial at seven Dutch radiotherapy centres . We enrolled patients with intermediate-risk to high-risk T1b-T4NX-N0MX-M0 localised prostate cancer , a prostate-specific antigen concentration of 60 μg/L or less , and a WHO performance status of 0 - 2 . We used a web-based application to r and omly assign ( 1:1 ) patients to either hypofractionated radiotherapy of 64·6 Gy ( 19 fractions of 3·4 Gy , three fractions per week ) or conventionally fractionated radiotherapy of 78·0 Gy ( 39 fractions of 2·0 Gy , five fractions per week ) . Based on an estimated α/β ratio for prostate cancer of 1·5 Gy , the equivalent total dose in fractions of 2·0 Gy was 90·4 Gy for hypofractionation compared with 78·0 Gy for conventional fractionation . The primary endpoint was relapse-free survival . All analyses were done on an intention-to-treat basis in all eligible patients . The HYPRO trial completed recruitment in 2010 and follow-up is ongoing . This trial is registered with IS RCT N , number IS RCT N85138529 . FINDINGS Between March 19 , 2007 , and Dec 3 , 2010 , 820 patients were enrolled , of whom 804 were eligible and assessable for intention-to-treat analyses . Of these , 407 were assigned hypofractionated radiotherapy and 397 were allocated conventionally fractionated radiotherapy . 537 ( 67 % ) of 804 patients received concomitant and rogen deprivation therapy for a median duration of 32 months ( IQR 10 - 44 ) . Median follow-up was 60 months ( IQR 51 - 69 ) . Treatment failure was reported in 169 ( 21 % ) of 804 patients , 80 ( 20 % ) in the hypofractionation group and 89 ( 22 % ) in the conventional fractionation group . 5-year relapse-free survival was 80·5 % ( 95 % CI 75·7 - 84·4 ) for patients assigned hypofractionation and 77·1 % ( 71·9 - 81·5 ) for those allocated conventional fractionation ( adjusted hazard radio 0·86 , 95 % CI 0·63 - 1·16 ; log-rank p=0·36 ) . There were no treatment-related deaths . INTERPRETATION Hypofractionated radiotherapy was not superior to conventional radiotherapy with respect to 5-year relapse-free survival . Our hypofractionated radiotherapy regimen can not be regarded as the new st and ard of care for patients with intermediate-risk or high-risk prostate cancer . FUNDING Dutch Cancer Society Background Clinical data indicates that delivery of larger daily doses of radiation may improve the therapeutic ratio for prostate cancer compared to conventional fractionation . A phase II study of stereotactic body radiotherapy with real-time motion management and daily plan re-optimization for low to intermediate risk prostate cancer was undertaken to evaluate this hypothesis . This report details the toxicity and quality of life following treatment . Methods From 2009 to 2013 , 60 patients with T1–T2c prostate cancer with a Gleason score of 6 and PSA ≤ 15 or Gleason score of 7 and PSA ≤ 10 were enrolled . Patients with nodal metastases , an American Urological Association symptom score > 18 , or gl and size > 100 g were not eligible . Patients were treated to 37 Gy in 5 fractions . Early and late genitourinary and gastrointestinal toxicity were grade d based on NCI CTCAE v4.0 and quality of life was assessed by the American Urological Association symptom score , International Index of Erectile Function , and Exp and ed Prostate cancer Index Composite Short Form up to 36 months after treatment . Results After a median follow-up of 27.6 months , no grade 3 or greater genitourinary toxicity was observed . Four patients ( 6.7 % ) reported a late grade 2 genitourinary toxicity . One patient ( 1.7 % ) reported a late grade 3 gastrointestinal toxicity . Five patients ( 8.3 % ) developed a late grade 2 gastrointestinal toxicity . The median American Urological Association symptom score increased from 4.5 prior to treatment to 11 while on treatment ( p < 0.01 ) , but was 5 at 36 months post-treatment ( p = 0.65 ) . Median International Index of Erectile Function scores decreased from 19 to 17 over the course of follow-up ( p < 0.01 ) . Only median scores within the Exp and ed Prostate Cancer Index Composite Short Form sexual domain were significantly decreased at 36 months post-treatment ( 67.9 vs 45.2 , p = 0.02 ) . There was no significant difference in median score within the urinary , bowel , or hormonal domains at 36 months of follow-up . Conclusions Stereotactic body radiotherapy for low to intermediate risk prostate cancer is well tolerated with limited toxicity or decrease in quality of life . Longer follow-up is necessary to assess the efficacy of treatment . Trial registration Clinical trials.gov NCT00941915 Registered 17 June 2009 AIMS The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer . MATERIAL S AND METHODS Biopsy-confirmed prostate cancer patients were enrolled , provided that they had the following characteristics : initial prostate-specific antigen ( PSA ) ≤ 20 ng/ml , Gleason Score < 7 , International Prostate Symptom Score < 7 . The treatment schedule was 35 Gy in five fractions , delivered with volumetric modulated arcs with flattening filter free beams . Toxicity was recorded according to CTCAE criteria v4.0 . Biochemical failure was calculated according to the Phoenix definition . The Exp and ed Prostate Cancer Index Composite question naire was used to record health-related quality of life . RESULTS Between December 2011 and March 2015 , 90 patients were enrolled ( 53 low risk , 37 intermediate risk ) . The median age was 71 years ( range 48 - 82 ) . In total , 58 ( 64.5 % ) of the patients had Gleason Score=6 , the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml ( range 2.7 - 17.0 ) . Acute toxicity was mild , with 32.2 patients presenting grade 1 urinary toxicity and 32.2 % of patients presenting grade 2 urinary toxicity , mainly represented by urgency , dysuria and stranguria . Rectal grade 1 toxicity was found in 15.5 % of patients , whereas grade 2 toxicity was recorded in 6.6 % of patients . Regarding late toxicity , grade 1 proctitis was recorded in 11.1 % of patients and grade 1 urinary in 38.8 % ; only two events of grade 2 urinary toxicity were observed ( transient urethral stenosis , resolved by a 24 h catheterisation ) . At a median follow-up of 27 months ( 6 - 62 months ) only two intermediate risk patients experienced a biochemical failure . Health-related quality of life revealed a slight worsening in all the domains during treatment , with a return to baseline 3 months after treatment . CONCLUSIONS Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life PURPOSE Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology . The results of a prospect i ve trial of stereotactic body radiotherapy ( SBRT ) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented . METHODS AND MATERIAL S From 2003 through 2009 , 67 patients with clinical ly localized low-risk prostate cancer were enrolled . Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology . No patient received hormone therapy . Patient self-reported bladder and rectal toxicities were grade d on the Radiation Therapy Oncology Group scale ( RTOG ) . RESULTS Median follow-up was 2.7 years . There were no grade 4 toxicities . Radiation Therapy Oncology Group Grade 3 , 2 , and 1 bladder toxicities were seen in 3 % ( 2 patients ) , 5 % ( 3 patients ) , and 23 % ( 13 patients ) respectively . Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity . Urinary incontinence , complete obstruction , or persistent hematuria was not observed . Rectal Grade 3 , 2 , and 1 toxicities were seen in 0 , 2 % ( 1 patient ) , and 12.5 % ( 7 patients ) , respectively . Persistent rectal bleeding was not observed . Low- grade toxicities were substantially less frequent with QOD vs. QD dose regimen ( p = 0.001 for gastrointestinal and p = 0.007 for genitourinary ) . There were two prostate-specific antigen ( PSA ) , biopsy-proven failures with negative metastatic workup . Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94 % ( 95 % confidence interval , 85%-102 % ) . CONCLUSION Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent . PSA relapse-free survival compares favorably with other definitive treatments . The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer PURPOSE SpaceOAR , a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space , was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy . A total of 222 men were r and omized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles . The present study reports the final results with a median follow-up period of 3 years . METHODS AND MATERIAL S Cumulative ( Common Terminology Criteria for Adverse Events , version 4.0 ) toxicity was evaluated using the log-rank test . Quality of life ( QOL ) was examined using the Exp and ed Prostate Cancer Index Composite ( EPIC ) , and the mean changes from baseline in the EPIC domains were tested using repeated measures models . The proportions of men with minimally important differences ( MIDs ) in each domain were tested using repeated measures logistic models with prespecified thresholds . RESULTS The 3-year incidence of grade ≥1 ( 9.2 % vs 2.0 % ; P=.028 ) and grade ≥2 ( 5.7 % vs 0 % ; P=.012 ) rectal toxicity favored the spacer arm . Grade ≥1 urinary incontinence was also lower in the spacer arm ( 15 % vs 4 % ; P=.046 ) , with no difference in grade ≥2 urinary toxicity ( 7 % vs 7 % ; P=0.7 ) . From 6 months onward , bowel QOL consistently favored the spacer group ( P=.002 ) , with the difference at 3 years ( 5.8 points ; P<.05 ) meeting the threshold for a MID . The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years ( P<.05 ) , but the difference did not meet the MID threshold . At 3 years , more men in the control group than in the spacer group had experienced a MID decline in bowel QOL ( 41 % vs 14 % ; P=.002 ) and urinary QOL ( 30 % vs 17 % ; P=.04 ) . Furthermore , the control group were also more likely to have experienced large declines ( twice the MID ) in bowel QOL ( 21 % vs 5 % ; P=.02 ) and urinary QOL ( 23 % vs 8 % ; P=.02 ) . CONCLUSIONS The benefit of a hydrogel spacer in reducing the rectal dose , toxicity , and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period , providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy PURPOSE To investigate if stereotactic ablative radiotherapy ( SABR ) dose is associated with PSA at 3years ( PSA3y ) in the treatment of localized prostate cancer and to explore predictors of late genitourinary ( GU ) toxicity . MATERIAL S AND METHODS Three prospect i ve trials of SABR were undertaken at our institution : 1 ) 35Gy/5 fractions/29days ; 2 ) 40Gy/5 fractions/29days ; 3 ) 40Gy/5 fractions/11 or 29days . PSA3y was analyzed as a continuous variable . Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group ( RTOG ) late morbidity scheme . Univariate and multivariable regression analyses were conducted to assess the association between dose and PSA3y , and to explore predictors of late grade 2 + GU toxicity . RESULTS Median PSA3y was 0.64 ( intraquartile range ( IQR ) : 0.41 - 1.12 ) and 0.27 ( IQR : 0.12 - 0.55 ) ng/mL for patients treated with 35 and 40Gy respectively . A dose of 40Gy was an independent predictor of lower PSA3y on multivariable analysis ( p<0.001 ) . Dose of 40Gy ( odds ratio ( OR ) : 16.69 , 95%CI : 5.78 , 48.20 , p<0.001 ) and higher International Prostate Symptom Score ( OR : 1.01 , 95%CI : 1.04 , 1.16 , p=0.001 ) predicted for late grade 2 + GU toxicity on multivariable logistic regression . CONCLUSIONS This analysis suggests that higher SABR dose is associated with lower PSA3y . Strategies to allow safe SABR dose escalation should be further investigated PURPOSE To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer . METHODS AND MATERIAL S Men scoring ≥3 on the Vulnerable Elderly Scale ( VES ) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate . And rogen suppression was delivered for 12 months , and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks . The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity , with trial suspension specified if there were ≥6 of 15 patients ( 40 % ) or ≥3 of 15 ( 20 % ) who experienced grade ≥2 or ≥3 gastrointestinal ( GI ) or genitourinary ( GU ) toxicity , respectively . RESULTS Sixteen men were enrolled , with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment . One man was not treated owing to discovery of a synchronous primary rectal cancer . Four patients ( 26 % ) experienced grade ≥2 toxicity at 6 weeks after treatment . There were 9 of 15 ( 60 % ) who experienced grade ≥2 GI or GU toxicity and 4 of 15 ( 26 % ) grade ≥3 GI or GU toxicity at 6 months , and 5 of 15 ( 30 % ) grade ≥2 GI and GU toxicity at 6 months . A review of the 15 cases did not identify any remedial changes , thus the phase 1 criteria were not met . CONCLUSION This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual . Treatment factors , such as inclusion of pelvic lymph node radiation therapy , planning constraints , and treatment margins , or patient factors related to the specific frail elderly population may be contributing Introduction The optimal prostate stereotactic body radiation therapy ( SBRT ) dose-fractionation scheme is controversial . This study compares long-term quality of life ( QOL ) from two prospect i ve trials of prostate SBRT to investigate the effect of increasing dose ( NCT01578902 and NCT01146340 ) . Material and methods Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions , once per week . QOL was measured using the Exp and ed Prostate Cancer Index Composite at baseline and every 6 months . Fisher ’s exact test and generalized estimating equations were used to analyze proportions of patients with clinical ly significant change and longitudinal changes in QOL . Results One hundred fourteen patients were included , 84 treated with 35 Gy and 30 treated with 40 Gy . Median QOL follow-up was 56 months [ interquartile range ( IQR ) 46–60 ] and 38 months ( IQR 32–42 ) , respectively . The proportion of patients reporting clinical ly significant declines in average urinary , bowel , and sexual scores were not significantly different between dose levels , and were 20.5 vs. 24.1 % ( p = 0.60 ) , 26.8 vs. 41.4 % ( p = 0.16 ) , and 42.9 vs. 38.5 % ( p = 0.82 ) , respectively . Similarly , longitudinal analysis did not identify significant differences in QOL between treatment groups . Conclusion Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL BACKGROUND We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy ( SBRT ) for low ( LR ) and select intermediate risk ( IR ) prostate cancer ( PCa ) patients . PATIENTS AND METHODS Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b . For the phase I portion of the study patients in cohorts of 15 received 45 , 47.5 , or 50 Gray ( Gy ) in five fractions . Since the maximally tolerated dose was not met in the phase I study , an additional 47 patients received 50 Gy in five fractions in the phase II study . Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0 , quality of life , and outcome data was collected . RESULTS A total of 91 patients are included for analysis ; 63.7 % had NCCN IR and 36.3 % had LR PCa . At a median follow up of 54 months the actuarial freedom from biochemical failure was 100 % at 3 years and 98.6 % at 5 years . Actuarial distant metastasis free survival was 100 % at 3 and 5 years . Overall survival was 94 % at 3 years and 89.7 % at 5 years with no deaths attributed to PCa . Acute and late urinary grade ≥ III toxicity occurred in 0 % and 5.5 % of patients , respectively . Gastrointestinal ( GI ) acute and late toxicity of grade ≥ III occurred in 2 % and 7 % of patients , respectively . A total of four men experienced grade IV toxicity ( three GI , one genitourinary ) . CONCLUSION SBRT treatment results in excellent biochemical control rates at 5 years for LR and IR PCa patients although doses greater than 47.5 Gy in five fractions led to increased severe late toxicity Purpose Men with localized prostate cancer often are treated with external radiotherapy ( RT ) over 8 to 9 weeks . Hypofractionated RT is given over a shorter time with larger doses per treatment than st and ard RT . We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity . Patients and Methods We conducted a multicenter r and omized noninferiority trial in intermediate-risk prostate cancer ( T1 to 2a , Gleason score ≤ 6 , and prostate-specific antigen [ PSA ] 10.1 to 20 ng/mL ; T2b to 2c , Gleason ≤ 6 , and PSA ≤ 20 ng/mL ; or T1 to 2 , Gleason = 7 , and PSA ≤ 20 ng/mL ) . Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks . And rogen deprivation was not permitted with therapy . The primary outcome was biochemical- clinical failure ( BCF ) defined by any of the following : PSA failure ( nadir + 2 ) , hormonal intervention , clinical local or distant failure , or death as a result of prostate cancer . The noninferiority margin was 7.5 % ( hazard ratio , < 1.32 ) . Results Median follow-up was 6.0 years . One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the st and ard arm experienced BCF . Most of the events were PSA failures . The 5-year BCF disease-free survival was 85 % in both arms ( hazard ratio [ short v st and ard ] , 0.96 ; 90 % CI , 0.77 to 1.2 ) . Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the st and ard arm . No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity . Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity . Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer PURPOSE To evaluate the early and late health-related quality of life ( QOL ) outcomes among prostate cancer patients following stereotactic body radiation therapy ( SBRT ) . METHODS AND MATERIAL S Patient self-reported QOL was prospect ively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer . Data from the Exp and ed Prostate Cancer Index Composite ( EPIC ) instrument were obtained at baseline and at regular intervals up to 6 years . SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions . A short course of and rogen deprivation therapy was given to 14 % of patients . RESULTS Median follow-up was 3 years and 194 patients remained evaluable at 5 years . A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years . The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities . Sexual QOL decline was predominantly observed within the first 9 months , a pattern not altered by the use of and rogen deprivation therapy or patient age . CONCLUSION Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL . A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels . With a large number of patients evaluable up to 5 years following SBRT , it is unlikely that unexpected late adverse effects will manifest themselves PURPOSE Conventional radiotherapy ( C-RT ) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks . Pre clinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes . This trial was design ed to assess whether the efficacy of a hypofractionated radiotherapy ( H-RT ) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer . PATIENTS AND METHODS A total of 1,115 men with low-risk prostate cancer were r and omly assigned 1:1 to C-RT ( 73.8 Gy in 41 fractions over 8.2 weeks ) or to H-RT ( 70 Gy in 28 fractions over 5.6 weeks ) . This trial was design ed to establish ( with 90 % power and an α of .05 ) that treatment with H-RT results in 5-year disease-free survival ( DFS ) that is not worse than C-RT by more than 7.65 % ( H-RT/C-RT hazard ratio [ HR ] < 1.52 ) . RESULTS A total of 1,092 men were protocol eligible and had follow-up information ; 542 patients were assigned to C-RT and 550 to H-RT . Median follow-up was 5.8 years . Baseline characteristics were not different according to treatment assignment . The estimated 5-year DFS was 85.3 % ( 95 % CI , 81.9 to 88.1 ) in the C-RT arm and 86.3 % ( 95 % CI , 83.1 to 89.0 ) in the H-RT arm . The DFS HR was 0.85 ( 95 % CI , 0.64 to 1.14 ) , and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met ( P < .001 ) . Late grade 2 and 3 GI and genitourinary adverse events were increased ( HR , 1.31 to 1.59 ) in patients who were treated with H-RT . CONCLUSION In men with low-risk prostate cancer , the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks , although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes . PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen < /= 15 ng/mL were r and omly assigned to a total dose of either 70.2 Gray equivalents ( GyE ; conventional ) or 79.2 GyE ( high ) . No patient received and rogen suppression therapy with radiation . Local failure ( LF ) , biochemical failure ( BF ) , and overall survival ( OS ) were outcomes . Results A total of 393 men were r and omly assigned , and median follow-up was 8.9 years . Men receiving high-dose radiation therapy were significantly less likely to have LF , with a hazard ratio of 0.57 . The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4 % for conventional-dose and 16.7 % for high-dose radiation therapy ( P < .0001 ) . This difference held when only those with low-risk disease ( n = 227 ; 58 % of total ) were examined : 28.2 % for conventional and 7.1 % for high dose ( P < .0001 ) . There was a strong trend in the same direction for the intermediate-risk patients ( n = 144 ; 37 % of total ; 42.1 % v 30.4 % , P = .06 ) . Eleven percent of patients subsequently required and rogen deprivation for recurrence after conventional dose compared with 6 % after high dose ( P = .047 ) . There remains no difference in OS rates between the treatment arms ( 78.4 % v 83.4 % ; P = .41 ) . Two percent of patients in both arms experienced late grade > /= 3 genitourinary toxicity , and 1 % of patients in the high-dose arm experienced late grade > /= 3 GI toxicity . CONCLUSION This r and omized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation . This was achieved without an increase in grade > /= 3 late urinary or rectal morbidity 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 PURPOSE The effectiveness of stereotactic body radiotherapy ( SBRT ) for localized prostate cancer is tested . METHODS AND MATERIAL S A total of 1100 patients with clinical ly localized prostate cancer were enrolled in separate prospect i ve phase 2 clinical trials of SBRT from 8 institutions during 2003 - 11 and pooled for analysis . SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4 - 5 fractions . Patients were low-risk ( 58 % ) , intermediate-risk ( 30 % ) and high-risk ( 11 % ) . A short-course of and rogen deprivation therapy ( ADT ) was given to 14 % . PSA relapse defined as a rise > 2ng/ml above nadir was analyzed with the Kaplan Meier method . RESULTS With a median follow-up of 36months there were 49 patients with PSA failure ( 4.5 % ) , 9 of whom were subsequently determined to be benign PSA bounces . The 5-year biochemical relapse free survival ( bRFS ) rate was 93 % for all patients ; 95 % , 83 % and 78 % for GS ⩽6 , 7 and ⩾8 , respectively ( p=0.001 ) , and 95 % , 84 % and 81 % for low- , intermediate- and high-risk patients , respectively ( p<0.001 ) . No differences were observed with ADT ( p=0.71 ) or as a function of total dose ( p=0.17 ) . A PSA bounce of > 0.2ng/ml was noted among 16 % of patients . For 135 patients possessing a minimum of 5years follow-up , the 5-year bRFS rate for low- and intermediate-risk patients was 99 % and 93 % , respectively . CONCLUSION PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients . The current evidence supports consideration of SBRT among the therapeutic options for these patients PURPOSE To compare biochemical outcome and toxicities of two prospect i ve 5-fraction stereotactic ablative radiotherapy ( SABR ) studies in prostate cancer . MATERIAL S AND METHODS 84 patients in pHART3 received 35 Gy , 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone , once weekly . 4 mm and 5 mm PTV margins were used , respectively . Biochemical outcome , acute , late and cumulative genitourinary (GU)/gastrointestinal ( GI ) toxicities were compared . RESULTS Median follow-up was 74 and 36 months , respectively . Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml . 2- , 4- and 6-year biochemical relapse-free survival ( bRFS-2+nadir ) was 100 % , 98.7 % and 95.9 % in pHART3 ; 100 % , 100 % and not reached in pHART6 ( p=0.91 ) . There was one acute grade 3 GU ( retention ) and late grade 4 GI ( fistula ) toxicity in pHART3 , none in pHART6 . One patient in each study had persisting grade 2 + toxicity at the last follow-up . pHART6 patients had a greater grade 2 + cumulative GU ( 5 % versus 24.2 % ) and GI ( 7.6 % versus 26.2 % ) toxicities . CONCLUSIONS Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS , longer follow-up is needed to better estimate biochemical outcomes . There was a greater risk of grade 2 toxicity in pHART6 but not grade 3 + toxicities . Persisting toxicity at the last follow-up is similar BACKGROUND We tested our ability to approximate the dose ( 38 Gy ) , fractionation ( four fractions ) , and distribution of high-dose-rate ( HDR ) brachytherapy for prostate cancer with CyberKnife ( CK ) stereotactic body radiotherapy ( SBRT ) plans . We also report early clinical observations of CK SBRT treatment . METHODS AND MATERIAL S Ten patients were treated with CK . For each CK SBRT plan , an HDR plan was design ed using common contour sets and simulated HDR catheters . Planning target volume coverage , intraprostatic dose escalation , and urethra , rectum , and bladder exposure were compared . RESULTS Planning target volume coverage by the prescription dose was similar for CK SBRT and HDR plans , whereas percent of volume of interest receiving 125 % of prescribed radiation dose ( V125 ) and V150 values were higher for HDR , reflecting higher doses near HDR source dwell positions . Urethra dose comparisons were lower for CK SBRT in 9 of 10 cases , suggesting that CK SBRT may more effectively limit urethra dose . Bladder maximum point doses were higher with HDR , but bladder dose falloff beyond the maximum dose region was more rapid with HDR . Maximum rectal wall doses were similar , but CK SBRT created sharper rectal dose falloff beyond the maximum dose region . Second CK SBRT plans , constructed by equating urethra radiation dose received by point of maximum exposure of volume of interest to the HDR plan , significantly increased V125 and V150 . Clinical ly , 4-month post-CK SBRT median prostate-specific antigen levels decreased 86 % from baseline . Acute toxicity was primarily urologic and returned to baseline by 2 months . Acute rectal morbidity was minimal and transient . CONCLUSIONS It is possible to construct CK SBRT plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively |
555 | 24,676,468 | Neuroticism and the use of escapist coping strategies were positively associated with distress by multiple studies .
Social support was negatively associated with distress by several studies .
There is a paucity of research using positive emotional outcome measures ( e.g. well-being , positive affect , happiness or life satisfaction ) to quantify emotional adjustment .
Whilst some psychosocial variables appear to be consistently associated with distress for IVF patients , two-thirds of the variables tested to date do not appear to be associated with emotional adjustment . | BACKGROUND IVF treatment is usually stressful for patients , but individual differences in emotional response do exist .
Differences in the stress response may be related to reproductive outcomes as well as to the development of psychiatric problems .
This review collates research exploring which psychosocial factors ( e.g. personality traits and coping strategies ) are associated with the emotional adjustment of IVF patients .
The aim is to reveal what is currently known about risk and protective factors for coping with the stress of IVF treatment and where further enquiry would be most beneficial . | OBJECTIVES The aim of these two studies was to evaluate the effectiveness of the Mindful Self-Compassion ( MSC ) program , an 8-week workshop design ed to train people to be more self-compassionate . METHODS Study 1 was a pilot study that examined change scores in self-compassion , mindfulness , and various wellbeing outcomes among community adults ( N = 21 ; mean [ M ] age = 51.26 , 95 % female ) . Study 2 was a r and omized controlled trial that compared a treatment group ( N = 25 ; M age = 51.21 ; 78 % female ) with a waitlist control group ( N = 27 ; M age = 49.11 ; 82 % female ) . RESULTS Study 1 found significant pre/post gains in self-compassion , mindfulness , and various wellbeing outcomes . Study 2 found that compared with the control group , intervention participants reported significantly larger increases in self-compassion , mindfulness , and wellbeing . Gains were maintained at 6-month and 1-year follow-ups . CONCLUSIONS The MSC program appears to be effective at enhancing self-compassion , mindfulness , and wellbeing The mechanisms underlying the association between positive emotions and physical health remain a mystery . We hypothesize that an upward-spiral dynamic continually reinforces the tie between positive emotions and physical health and that this spiral is mediated by people ’s perceptions of their positive social connections . We tested this overarching hypothesis in a longitudinal field experiment in which participants were r and omly assigned to an intervention group that self-generated positive emotions via loving-kindness meditation or to a waiting-list control group . Participants in the intervention group increased in positive emotions relative to those in the control group , an effect moderated by baseline vagal tone , a proxy index of physical health . Increased positive emotions , in turn , produced increases in vagal tone , an effect mediated by increased perceptions of social connections . This experimental evidence identifies one mechanism — perceptions of social connections — through which positive emotions build physical health , indexed as vagal tone . Results suggest that positive emotions , positive social connections , and physical health influence one another in a self-sustaining upward-spiral dynamic OBJECTIVE To present and determine the impact of the Mindfulness-Based Program for Infertility ( MBPI ) . DESIGN Controlled clinical trial . SETTING University research unit . PATIENT(S ) Fifty-five infertile women completed the MBPI , and 37 infertile women were assigned to a control group . INTERVENTION(S ) The MBPI includes 10 weekly sessions , in a group format , with a duration of about 2 hours each ( men attend three sessions ) . MAIN OUTCOME MEASURE(S ) St and ardized measures of depression , state anxiety , entrapment , defeat , internal and external shame , experiential avoidance , mindfulness , self-compassion , and infertility self-efficacy were endorsed pre- and post-MBPI . RESULT ( S ) The MBPI group and the control group were shown to be equivalent at baseline . By the end of the MBPI , women who attended the program revealed a significant decrease in depressive symptoms , internal and external shame , entrapment , and defeat . Inversely , they presented statistically significant improvement in mindfulness skills and self-efficacy to deal with infertility . Women in the control group did not present significant changes in any of the psychological measures , except for a decrease in self-judgment . CONCLUSION ( S ) Increasing mindfulness and acceptance skills , as well as cognitive decentering from thoughts and feelings , seem to help women to experience negative inner states in new ways , decreasing their entanglement with them and thus their psychological distress . Data suggest that the MBPI is an effective psychological intervention for women experiencing infertility OBJECTIVE To determine whether cognitive behavior therapy ( CBT ) , which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea ( FHA ) , could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA . DESIGN R and omized controlled trial . SETTING Clinical research center at an academic medical university . PATIENT(S ) Seventeen women with FHA were r and omized either to CBT or observation . INTERVENTION(S ) CBT versus observation . MAIN OUTCOME MEASURE(S ) Circulatory concentrations of cortisol , leptin , thyroid-stimulating hormone ( TSH ) , total and free thyronine ( T(3 ) ) , and total and free thyroxine ( T(4 ) ) before and immediately after completion of CBT or observation . ( Each woman served as her own control . ) RESULT ( S ) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA . There were no changes in cortisol , leptin , TSH , T(3 ) , or T(4 ) levels in women r and omized to observation . Women treated with CBT showed increased levels of leptin and TSH , but their levels of T(3 ) and T(4 ) remained unchanged . CONCLUSION ( S ) In women with FHA , CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not . We conclude that a cognitive , nonpharmacologic approach aim ed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA . CLINICAL TRIAL REGISTRATION NUMBER NCT01674426 BACKGROUND This study explores the differences in prenatal maternal expectations , coping re sources and maternal stress between first time mothers of IVF twins and first time mothers of spontaneously conceived twins . The role of prenatal maternal expectations in the prediction of maternal stress was examined , as well as the mediating and moderating effect of coping re sources on the association between pregnancy-type group and maternal stress . METHOD Mothers of twins from various regions in Israel were included in this prospect i ve and cross-sectional study in which 88 mothers of IVF-conceived twins and 98 mothers of spontaneously conceived twins were interviewed twice . First , at 33 - 36 weeks of their pregnancy they completed a socio-demographic question naire and the maternal expectations question naire ; then at 6 months after birth they completed a question naire regarding the delivery and medical condition of the infants , and their coping re sources and maternal stress . RESULTS Compared with mothers who conceived spontaneously , IVF mothers had more positive prenatal maternal expectations , but poorer coping re sources and higher levels of maternal stress 6 months after birth . Maternal expectations had no predictive power regarding maternal stress , although the mother 's coping re sources were significantly related to maternal stress and mediated the association between pregnancy type and maternal stress . CONCLUSIONS IVF-pregnant women bearing twins should be considered a high-risk group . Early identification of these mothers is essential for timely psychosocial interventions in order to enhance their re sources and decrease maternal stress . Further longitudinal studies are required to determine causality in more ethnically-diverse mothers of twins This study examined the correlation between various coping strategies and sexual functioning and the likelihood of conception from in vitro fertilization ( IVF ) . Self-reported question naires were distributed r and omly among the 102 women enrolled in an IVF program , 96 of whom were recruited . Of the studied parameters , positive reinterpretation , and growth , and active coping strategies were found to be positively associated with sexual functioning , while there was a significantly ( p < .05 ) adverse influence of planning and self-restraint . Being sexually active during the IVF-treatment period was found to be positively associated ( p < .05 ) with the likelihood of conception and with adaptive coping strategies Recent scientific work has established both a theoretical basis and strong empirical evidence for a causal impact of social relationships on health . Prospect i ve studies , which control for baseline health status , consistently show increased risk of death among persons with a low quantity , and sometimes low quality , of social relationships . Experimental and quasi-experimental studies of humans and animals also suggest that social isolation is a major risk factor for mortality from widely varying causes . The mechanisms through which social relationships affect health and the factors that promote or inhibit the development and maintenance of social relationships remain to be explored BACKGROUND IVF treatment involves a re assessment of issues concerning autonomy and relatedness . This study aims to extend prior studies on the psychological impact of IVF/ICSI by study ing the association between the personality dimensions of Self-Criticism and Dependency with the psychological well-being and quality of the couple relationship for women starting their first IVF treatment . METHODS This is a cross-sectional study of 68 women starting their first IVF treatment at the Leuven University Fertility Centre of the University of Leuven , Belgium . All women were administered vali date d self-report measures assessing Self-Criticism and Dependency , negative life events , psychological well-being , relationship satisfaction , and relationship and sexual concerns . Pearson 's correlation coefficients were calculated between all study variables , followed by four separate hierarchical multiple regression analyses for psychological well-being , relationship satisfaction , and relationship and sexual concerns . RESULTS High Self-Criticism was negatively associated with psychological well-being ( r = -0.63 , P < 0.001 ) and relationship satisfaction ( r = -0.29 , P < 0.05 ) , and positively associated with relationship ( r = 0.39 , P < 0.01 ) and sexual ( r = 0.37 , P < 0.01 ) concerns . High Dependency was negatively associated with psychological well-being ( r = -0.30 , P < 0.05 ) , not significantly associated with relationship satisfaction and relationship concerns , and positively related to sexual concerns ( r = 0.31 , P < 0.05 ) . CONCLUSIONS This cross-sectional study suggests that the personality dimensions of Self-Criticism and Dependency may enhance our underst and ing of the psychological well-being and quality of the couple relationship of women starting their first IVF treatment . However , further prospect i ve research on this topic is needed BACKGROUND The aim of this study was to gain more insight into long-term psychological adjustment to IVF in women . METHODS In a prospect i ve cohort study , 298 women entering their first IVF treatment cycle ( including ICSI ) completed st and ardized psychological question naires before the start of the treatment , just after the last treatment cycle , and 6 months and 3 - 5 years after the last treatment cycle . The main outcome measures were state anxiety , depression and mode of adaptation to unsuccessful IVF . RESULTS Anxiety and depression were found at follow-up to return to baseline levels following treatment not result ing in a live birth , after an initial increase during treatment . On the contrary , treatment result ing in a live birth was found to lead to a more positive long-term emotional status . Women who focused on new life goals as a mode of adaptation 3 - 5 years after IVF without a live birth showed lower levels of anxiety and depression compared with those who persisted in their attempts to get pregnant . CONCLUSIONS Treatment that result ed in a live birth led to more positive emotional adjustment . In addition , most women who did not give birth to a child after treatment adjusted well psychologically . Positive adjustment was related to developing new life goals rather than persisting in attempts to get pregnant . Helping women to change life goals after ab and oning treatment might have beneficial effects on the adaptation process Objective : In an earlier study , positive emotional style ( PES ) was associated with resistance to the common cold and a bias to underreport ( relative to objective disease markers ) symptom severity . This work did not control for social and cognitive factors closely associated with PES . We replicate the original study using a different virus and controls for these alternative explanations . Methods : One hundred ninety-three healthy volunteers ages 21 to 55 years were assessed for a PES characterized by being happy , lively , and calm ; a negative emotional style ( NES ) characterized by being anxious , hostile , and depressed ; other cognitive and social dispositions ; and self-reported health . Subsequently , they were exposed by nasal drops to a rhinovirus or influenza virus and monitored in quarantine for objective signs of illness and self-reported symptoms . Results : For both viruses , increased PES was associated with lower risk of developing an upper respiratory illness as defined by objective criteria ( adjusted odds ratio comparing lowest with highest tertile = 2.9 ) and with reporting fewer symptoms than expected from concurrent objective markers of illness . These associations were independent of prechallenge virus-specific antibody , virus type , age , sex , education , race , body mass , season , and NES . They were also independent of optimism , extraversion , mastery , self-esteem , purpose , and self-reported health . Conclusions : We replicated the prospect i ve association of PES and colds and PES and biased symptom reporting , extended those results to infection with an influenza virus , and “ ruled out ” alternative hypotheses . These results indicate that PES may play a more important role in health than previously thought . BMI = body mass index ; CI = confidence interval ; NES = negative emotional style ; PES = positive emotional style ; RV = rhinovirus ; TCID = Tissue Culture Infectious Dose Research ers have documented the consequences of both expressing and suppressing emotion using between-subjects design s. It may be argued , however , that successful adaptation depends not so much on any one regulatory process , but on the ability to flexibly enhance or suppress emotional expression in accord with situational dem and s. We tested this hypothesis among New York City college students in the aftermath of the September 11th terrorist attacks . Subjects ' performance in a laboratory task in which they enhanced emotional expression , suppressed emotional expression , and behaved normally on different trials was examined as a prospect i ve predictor of their adjustment across the first two years of college . Results supported the flexibility hypothesis . A regression analysis controlling for initial distress and motivation and cognitive re sources found that subjects who were better able to enhance and suppress the expression of emotion evidence d less distress by the end of the second year . Memory deficits were also observed for both the enhancement and the suppression tasks , suggesting that both processes require cognitive re sources Few prospect i ve studies have examined the relationship between social support and psychological distress and depressive symptoms in adolescents . The aims of this study were to test whether social support is protective against psychological distress and depressive symptoms in an ethnically diverse population of adolescents and whether differences in support are reflected by ethnic differences in psychological distress and depressive symptoms . Based on a longitudinal survey of 821 adolescents , this study found low levels of social support from family members was prospect ively associated with depressive symptoms ( OR = 2.25 , 95 % CI 1.43 - 3.54 ) . Compared with White UK pupils , Black pupils were less likely to display psychological distress ( OR = 0.21 , 95 % CI 0.09 - 0.51 ) . However , social support did not explain the ethnic variations in psychological distress . Family environment may be a more consistent source of support compared with support from peers . The lower risk of psychological distress among Black pupils compared to White pupils requires further investigation OBJECTIVE To extend existing research on the psychological impact of IVF by study ing the association between the psychosocial factors of self-criticism and dependency , and romantic attachment , with the well-being and relationship satisfaction of couples across the different phases of IVF/intracytoplasmic sperm injection ( ICSI ) treatment . DESIGN Prospect i ve , three-wave study ( i.e. , from start of IVF/ICSI treatment , to 3- and 6-month follow-up ) . SETTING University hospital . PATIENT(S ) Seventy couples in IVF/ICSI treatment . INTERVENTION(S ) Psychometric tests were administered at first visit of IVF/ICSI treatment , and at 3- and 6-month follow-up . MAIN OUTCOME MEASURE(S ) Psychological well-being , relationship satisfaction . RESULT ( S ) Results demonstrated that preexisting psychosocial factors such as self-criticism , dependency , and romantic attachment are more important factors for psychological well-being and relationship satisfaction during IVF/ICSI than gender and treatment-related factors such as duration of fertility problems . In addition , multilevel analysis , a statistical method that is required for the analysis of longitudinal couple data and decomposes variation in three levels ( i.e. , time , individuals , and couples ) , showed more variation in psychological well-being and relationship satisfaction between couples , than between individuals and different time measurements . CONCLUSION ( S ) Preexisting personality factors and being embedded within a certain couple relationship are important factors for the psychological well-being and relationship satisfaction during IVF/ICSI OBJECTIVE To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET . DESIGN Controlled , prospect i ve clinical study . SETTING The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology , University of Modena . PATIENT(S ) Forty-nine infertile women consecutively admitted to st and ard superovulation treatment . Mean age was 33.9 years , duration of infertility was 6.3 years . Reasons for assisted reproduction were mechanical factor in 22 cases , sperm problem in 9 cases , and endocrine disorder in 6 cases . In 12 cases , infertility was unexplained . More than 55 % already had an IVF-ET attempt . INTERVENTION(S ) The day of oocyte pick-up , subjects were su bmi tted to Stroop Color and Word test , a task measuring the ability to cope with a cognitive stressor , involving attentional and sympathoadrenal systems . Systolic ( SBP ) and diastolic blood pressure , as well as heart rate ( HR ) were measured at baseline , during the test , and 10 minutes after the end of testing . MAIN OUTCOME MEASURE(S ) The evidence of a biochemical pregnancy ( beta-hCG value 12 days after ET ) define the success and failure groups . RESULT ( S ) Sixteen women ( 33 % ) had a biochemical pregnancy , 12 also had ultrasound evidence . Eight gave birth to healthy infants . Age , education , causes , and duration of infertility were similar in the success and failure groups . The latter were more involved in a job outside home than the former . Moreover , they had a lower number of both fertilized oocytes and transferred embryos . In response to the Stroop test , every subject reported an increase of cardiovascular parameters . However , women becoming pregnant showed a lower response of both SBP and HR than women who failed . CONCLUSION ( S ) Both a major cardiovascular vulnerability to stress and working outside home are associated to a poor outcome of IVF-ET treatment OBJECTIVE To develop a reliable , valid instrument to evaluate perceived infertility-related stress . DESIGN Prospect i ve study . SETTING University-affiliated teaching hospital . PATIENT(S ) Consecutively referred patients ( 1,153 women and 1,149 men ) seen for infertility treatment . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Participants ' infertility-related stress was assessed by written question naire using the Fertility Problem Inventory . Current levels of anxiety , depression , and marital satisfaction also were determined . RESULT ( S ) Women described greater global stress than men and higher specific stress in terms of social concerns , sexual concerns , and need for parenthood . Both men and women facing male infertility reported higher global stress and more social and sexual concerns than men and women experiencing female infertility . Social , sexual , and relationship concerns related to infertility were more effective predictors of depression and marital dissatisfaction than expressed needs for parenthood or attitudes toward child-free living . CONCLUSION ( S ) The Fertility Problem Inventory provides a reliable measure of perceived infertility-related stress and specific information on five separate domains of patient concern . Patterns of infertility-related stress differed depending on gender , fertility history , and infertility diagnosis . Among patients receiving treatment , social , sexual , and relationship concerns appear central to current distress . Counseling interventions that target these domains appear likely to offer maximal therapeutic benefit OBJECTIVE Australian women conceiving with ART are at fourfold risk of admission to early parenting treatment programs compared with those conceiving spontaneously . This study aim ed to identify prevalence and determinants of antenatal mood disturbance and other risks for early parenting difficulties after assisted conception . DESIGN A prospect i ve longitudinal investigation from conception to 18 months postpartum using telephone interviews and self-report question naires . SETTING Melbourne IVF and Royal Women 's Hospital Reproductive Services , Victoria , Australia . PATIENT(S ) A consecutive cohort of English-speaking women with ultrasound-confirmed ART-conceived pregnancies . MAIN OUTCOME MEASURE(S ) St and ardized psychometric measures of mood , quality of marital relationship , mother-to-fetus emotional attachment , and personality . INTERVENTION(S ) None . RESULT ( S ) Of the 288 women with confirmed pregnancies , 239 were contactable , and 183 ( 77 % ) were recruited , 95 % of whom completed both early and late pregnancy assessment s. Participants were socioeconomically advantaged , had very good pregnancy health , exceptional marital relationships , normal personality styles , and intense affectionate attachment to the fetus . Very few ( < 5 % ) had clinical ly significant mood disturbance in late pregnancy . CONCLUSION ( S ) There were low rates of antenatal mood disturbance and other risk factors for postpartum depression . Pregnancy and motherhood might be idealized after ART conception , and preparation for the realities of infant care might then be insufficient OBJECTIVE To describe rate of and risks for residential early parenting service ( REPS ) admissions in women with infants conceived with assisted reproductive technology ( ART ) . DESIGN A prospect i ve study of women who conceived with ART . Self-report telephone interview and question naire data were collected in two pregnancy and three postpartum waves . SETTING Melbourne IVF and Royal Women 's Hospital Reproductive Services , Victoria , Australia . PATIENT(S ) A consecutive cohort of women with ART pregnancies . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) REPS admission up to 18 months postpartum . RESULT ( S ) Of 239 eligible women . 183 ( 77 % ) were recruited , six experienced pregnancy loss , and 153/177 ( 86 % ) were retained . In total , 17 % ( 26/153 ) of participants were admitted to a REPS , 3.37 times more than the population admission rate of 5.05 % . Admission risk was increased by primiparity , inadequate breastfeeding advice , low caregiving confidence when discharged from maternity hospital , lower early postpartum mood , unsettled infant behavior , and insufficient help from others . CONCLUSION ( S ) Compared with spontaneous conception , women who conceived with ART are at elevated risk of early parenting difficulties . Early interventions to address breastfeeding difficulties , management of unsettled infant behavior , social isolation , and postpartum anxiety are indicated To replicate and extend the finding that distraction facilitates between session anxiety reduction ( ) , 27 spider phobics underwent three 10-min sessions of in vivo exposure followed by one 10-min exposure session at a 4-week follow-up , while having either stimulus-relevant focused conversation or stimulus-irrelevant distracting conversation with the experimenter . Physiological arousal and subjective anxiety were measured during exposure , and self-efficacy , perceived control and performance on a behavioural task were measured at pre-treatment , post session-3 , and follow-up . Monitoring and blunting coping styles were also measured at pre-treatment to assess their impact on treatment outcome . Despite equal physiological activation between the groups , those who underwent distracted exposure showed greater reductions in subjective fear within and between sessions , and showed greater increases in self-efficacy ratings , internal perceived control and performance on a behavioural task . Coping style did not interact with the effect of distraction or focusing during exposure , however blunters had less subjective anxiety reduction overall , particularly when they underwent focused exposure . Results are discussed in terms of the emotional processing model and self-efficacy theory OBJECTIVE To examine the relationship between stress and IVF outcome in women and to compare prospect i ve ratings of IVF stress to retrospective ratings . DESIGN Women completed daily stress ratings for one complete IVF cycle . Three days after the pregnancy test women completed a question naire that asked them to recall the stress of IVF . Based on the results of treatment , women were assigned to the nonpregnant ( n = 23 ) or pregnant ( n = 17 ) group and their daily stress ratings were compared . In addition , prospect i ve and retrospective ratings were compared . RESULTS The nonpregnant group reported more stress during specific stages of IVF and had a poorer biologic response to treatment than the pregnant group . It also was found that women recalled the stress of the waiting period as greater than their ongoing experience of it as measured by their daily ratings . CONCLUSIONS The pattern of differences between the nonpregnant and pregnant group on stress and biologic factors indicates that stress is related to IVF outcome . Certain data suggest that negative feedback about the progress of treatment communicated to patients responding poorly to IVF ( nonpregnant group ) may have increased their stress level . However , the direction of causality between stress and IVF outcome remains speculative . Differences between prospect i ve and retrospective stress ratings may reflect women 's attempt to cope with the strain of the waiting period OBJECTIVE To examine whether women 's baseline coping strategies are associated with IVF outcomes . Psychologic factors have been found to be prospect ively associated with the outcome of IVF treatments in several studies . However , the exact role of coping strategies , which are modifiable , remains unclear . Problem-focused coping may be more adaptive for controllable situations , whereas emotion-focused coping ( EFC ) may be more adaptive for uncontrollable situations , such as most stages of IVF treatment . DESIGN Prospect i ve study . Coping strategies were assessed before IVF treatment began . SETTING Infertility and IVF unit in a university-affiliated tertiary medical center . PATIENT(S ) Eighty-eight women undergoing IVF treatment in our unit . MAIN OUTCOME MEASURE(S ) Pregnancy . RESULT ( S ) Of 88 women participating in the study , 23.9 % became pregnant . In the male and female factor infertility groups , the EFC strategy of " letting go " was positively and significantly associated with pregnancy . Adjusting for age , cause of infertility , and number of cycles , the relative risk for pregnancy by " letting go " was 1.88 ( 95 % confidence interval 1.1 - 3.2 ) . CONCLUSION ( S ) These findings support the notion that in the context of a low-control situation such as IVF treatment , women who try to be actively in control may pay a higher price in terms of pregnancy probabilities . Means of increasing " letting go " are discussed Objective . To assess which personality traits are associated with depressive and /or anxiety disorders in infertile women and men undergoing in vitro fertilization ( IVF ) . Design . Prospect i ve study . Setting . A university hospital in Sweden . Population . A total of 856 eligible women and men , 428 couples , were approached to participate . Overall 643 ( 75.1 % ) subjects filled out the Swedish Universities Scales of Personality ( SSP ) question naire . The response rates were 323 women ( 75.5 % ) and 320 men ( 74.8 % ) . Methods . The SSP , a self‐rating personality trait question naire , was used for evaluation . Main outcome measures . Personality traits associated with depression and /or anxiety disorders . Results . Higher mean scores on all neuroticism‐related personality traits were found in women and men with depressive and /or anxiety disorders compared to women and men with no diagnosis . High scores of neuroticism and a negative pregnancy test after IVF were associated with depressive and /or anxiety disorders among women . Among men , high scores of neuroticism and unexplained or male infertility factor were associated with depressive and /or anxiety disorders . High neuroticism scores were negatively associated with live birth ( p < 0.05 ) . Conclusion . High scores on neuroticism‐related personality traits were associated with depressive and /or anxiety disorders in women and men undergoing IVF BACKGROUND : We performed this study to determine the beneficial effects of viewing an animated cartoon and playing with a favorite toy on preoperative anxiety in children aged 3 to 7 years in the operating room before anesthesia induction . METHODS : One hundred thirty children aged 3 to 7 years with ASA physical status I or II were enrolled . Subjects were r and omly assigned to 1 of 3 groups : group 1 ( control ) , group 2 ( toy ) , and group 3 ( animated cartoon ) . The children in group 2 were asked to bring their favorite toy and were allowed to play with it until anesthesia induction . The children in group 3 watched their selected animated cartoon until anesthesia induction . Children ’s preoperative anxiety was determined by the modified Yale Preoperative Anxiety Scale ( mYPAS ) and parent-recorded anxiety Visual Analog Scale ( VAS ) the night before surgery , in the preanesthetic holding room , and just before anesthesia induction . RESULTS : In the preanesthetic holding room , the group 2 mYPAS and parent-recorded anxiety VAS scores were significantly lower than those of groups 1 and 3 ( mYPAS : P = 0.007 ; parent-recorded anxiety VAS : P = 0.02 ) . In the operating room , the children in group 3 had the lowest mYPAS and parent-recorded anxiety VAS scores among the 3 groups ( mYPAS : P < 0.001 ; parent-recorded anxiety VAS : P < 0.001 ) . In group 3 , the mYPAS and parent-recorded anxiety VAS scores of only 3 and 5 children were increased in the operating room compared with their scores in the preanesthetic holding room , whereas the anxiety scores of 32 and 34 children in group 1 and 25 and 32 children in group 2 had increased ( P < 0.001 ) . The number of children whose scores indicated no anxiety ( mYPAS score < 30 ) in the operating room was 3 ( 7 % ) , 9 ( 23 % ) , and 18 ( 43 % ) in groups 1 , 2 , and 3 , respectively ( P < 0.001 ) . CONCLUSIONS : Allowing the viewing of animated cartoons by pediatric surgical patients is a very effective method to alleviate preoperative anxiety . Our study suggests that this intervention is an inexpensive , easy to administer , and comprehensive method for anxiety reduction in the pediatric surgical population |
556 | 32,081,117 | The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence .
Injectable oxytetracycline effectively controlled BRD compared with no antibiotics ; however , it was less effective than macrolide treatment .
Because oxytetracycline is already commonly used to prevent , control , and treat BRD in groups of feedlot cattle , the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective | We conducted a systematic review and network meta- analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease ( BRD ) in beef cattle on feedlots . | The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals . Comparisons were made among calves receiving an " on-arrival " injection of tilmicosin , calves receiving a single injection of long-acting oxytetracycline , and calves receiving no prophylaxis . Morbidity and mortality attributable to pneumonia , morbidity and mortality attributable to all causes , and case fatality were significantly lower in the group of calves that received tilmicosin , compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic . Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis , compared with those that received no antibiotic on arrival at the feedlot . Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline . Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group . The majority of mortalities were attributable to fibrinous pneumonia ( 31/34 ) . Important bacterial isolates ( Pasteurella spp , Haemophilus somnus , Actinomyces pyogenes ) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia . However , bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates The objectives of this study were to determine ( i ) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease ( BRD ) and treated with gamithromycin ( Zactran ( ® ) ) at the label dose and ( ii ) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid ( PELF ) effect compartment . The study design was a prospect i ve , blinded , r and omized clinical trial utilizing three groups of 60 ( 362 - 592 lb ) steers/bulls r and omly allocated within origin to sham injection or gamithromycin mass medication . Cattle were evaluated daily for signs of BRD by a veterinarian blinded to treatment . Animals meeting the BRD case definition were enrolled and allocated to a sample collection scheme consisting of sample s for bacterial isolation ( bronchoalveolar lavage fluid and nasopharyngeal swabs ) and gamithromycin concentration determination ( PELF and plasma ) . Gamithromycin susceptibility of M. haemolytica ( n = 287 ) and P. multocida ( n = 257 ) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16 μg/mL. A two-compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in PELF was developed using rich data sets from published and unpublished studies . The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values . The result ing parameter estimates were used to simulate full time-concentration profiles for each animal in this study . These profiles were analyzed using noncompartmental methods so that PK/PD indices ( AUC24 /MIC , AUC∞ /MIC , CMAX /MIC ) could be calculated for plasma and PELF ( also T > MIC ) for each individual . The calculated PK/PD indices were indicative that for both M. haemolytica and P. multocida a higher drug exposure in terms of concentration , and duration of exposure relative to the MIC of the target pathogen , was favorable to a successful case outcome . A significant association was found between treatment success and PELF AUC0 - 24 /MIC for P. multocida . The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports . Ultimately , the findings from this study indicate that higher PK/PD indices were predictive of positive treatment outcomes Three studies were conducted to determine and confirm the effective dosage rate of ceftiofur crystalline-free acid sterile suspension ( CCFA-SS , 200 mg ceftiofur equivalents [CE]/ml ) , a long-acting ceftiofur formulation , for control and treatment of bovine respiratory disease ( BRD ) . In each study , CCFA-SS was administered once by subcutaneous ( SC ) injection in the middle third of the posterior aspect of the ear . Study 1 was conducted using an intratracheal challenge with Mannheimia ( formerly Pasteurella ) haemolytica and dosages ranging from 0 to 8.8 mg CE/kg to select a dosage for further field testing . In Study 2 , a single dose of CCFA-SS at 0.0 , 4.4 , or 6.6 mg CE/kg was administered when uniform clinical signs of BRD were present in feedlot cattle . Study 3 was conducted in several feedlots to evaluate the efficacy , practicality , and safety of CCFA-SS at 4.4 or 6.6 mg CE/kg compared with a placebo control or tilmicosin for preemptive control of BRD . In Study 1 , the effective dose was determined to be 5.35 mg CE/kg ; therefore , 4.4 and 6.6 mg CE/kg were selected as the dosages for further field testing . Administration of CCFA-SS at 4.4 or 6.6 mg CE/kg improved treatment success compared with negative controls ( P < or = .05 for both doses ) in Study 2 . In Study 3 , a single administration of 4.4 or 6.6 mg CE/kg was comparable to tilmicosin ( P < .001 ) and was significantly better than placebo ( P < .001 ) for the control of BRD . Using the ear as an administration site was acceptable under field conditions and was well tolerated by all animals . These studies demonstrated that a single administration of CCFA-SS by SC injection in the middle third of the posterior aspect of the ear at 4.4 or 6.6 mg CE/kg is effective , safe , and practical for preemptive control and treatment of the bacterial component of BRD in feedlot cattle . Administration in an inedible tissue results in a short withdrawal time and no injection-site trimming at slaughter Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Three studies conducted at feedlots in Colorado , Idaho , and Texas examined the comparative efficacy of tulathromycin injectable solution for the treatment of cattle at high risk of developing undifferentiated bovine respiratory disease ( BRD ) . Each study r and omly allocated 250 calves to receive tulathromycin at 2.5 mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg ( Colorado site ) or florfenicol at 40 mg/kg ( Idaho and Texas sites ) on arrival at the feedlot . Calves were housed by treatment group in pens with 50 calves/pen . Beginning 3 days after antimicrobial treatment , cattle were observed for signs of BRD daily until harvest . In all three studies , the treatment success rates at 28 days after treatment and at harvest were significantly higher ( P < or = .013 ) for cattle treated with tulathromycin than for cattle treated with either tilmicosin or florfenicol . Fewer tulathromycin-treated cattle were removed from the group as " chronics " or " mortalities " at 28 days posttreatment ( P < or = .014 ) in all three studies . Tulathromycin demonstrated superior efficacy compared with tilmicosin and florfenicol when treating groups of high-risk cattle before the onset of signs of BRD OBJECTIVES To evaluate effects of tilmicosin when used in fever-based and metaphylactic treatment programs to attenuate acute undifferentiated bovine respiratory disease ( BRD ) in cattle that recently arrived at feedlots , and to evaluate the effects of tilmicosin for the treatment of BRD . DESIGN R and omized-block controlled study . ANIMALS 1,639 calves from livestock auctions . PROCEDURES Cattle were assigned to 3 groups . Cattle in the nonmedicated ( control ) group were not given antibiotics during processing . Cattle in the fever-based treatment group were given tilmicosin ( 10 mg/kg [ 4.5 mg/lb ] of body weight , s.c . ) during processing when their rectal temperature was > or = 40 C ( 104 F ) . All cattle in the metaphylactic treatment group were given tilmicosin ( 10 mg/kg , s.c . ) during processing . Calves with BRD were treated with tilmicosin ( 10 mg/kg , s.c . ) . RESULTS Morbidity rates in the metaphylactic ( 30.4 % ) and fever-based ( 44.7 % ) treatment groups were less than that for the nonmedicated group ( 54.8 % ) . Mortality rate for the metaphylactic group during the first 28 days ( 1.1 % ) and during the entire study ( 1.7 % ) was less than that for the nonmedicated group ( 3.3 and 4.6 % , respectively ) . Differences were not observed in therapeutic response rates among calves with BRD that were treated . CLINICAL IMPLICATION S Fever-based and metaphylactic treatment programs that used tilmicosin decreased the prevalence of BRD and improved growth of calves . Metaphylactic treatment decreased the number of fatalities caused by BRD in high-risk calves . Fever-based treatment was less effective than metaphylactic treatment for decreasing the prevalence of BRD in newly arrived cattle Feedlot calves ( n = 3784 ) were systematic ally r and omized and allocated in a 2 × 2 factorial study to receive metaphylactic oxytetracycline ( OTC ) on arrival or no antimicrobial , as well as florfenicol once subcutaneously or twice intramuscularly ( 48 h apart ) if diagnosed with bovine respiratory disease ( BRD ) . Calves of different treatment groups were comingled and followed from placement to re-implantation ( ~100 days ) . Animals receiving OTC had a reduced risk of BRD , an increased risk of arthritis , and no significant differences in average daily gain , BRD relapse , overall mortality , or BRD mortality . There were no significant differences between treatment protocol s. Deep nasal swabs ( n = 233 ) taken at arrival ( n = 122 ) , treatment ( n = 77 ) , and swabs from lungs and joints at postmortem ( n = 34 ) were cultured for Mycoplasma bovis from 61 animals ill or dying of chronic pneumonia and arthritis and from 61 healthy calves . There was significant variation in diversity among isolates ( n = 51 ) between study years and different cattle . Metaphylaxis or antimicrobial treatment did not affect the diversity of isolates . Except for tilmicosin , isolates were largely susceptible to tested antimicrobials R and omized controlled trials ( RCTs ) are the gold st and ard for evaluating efficacy of treatments under real world conditions and , as such , it is important that they are conducted with method ological rigour to prevent biased results . Many medical journals have adopted a st and ard checklist for reporting of RCTs , the CONSORT statement . The objective of this study was to evaluate clinical trials in livestock population s to assess method ological quality and completeness of reporting and to investigate the association between these criteria and treatment effects . A total of 100 clinical trials published between 2006 and 2008 in the English language were r and omly selected . For each trial , 2 review ers independently completed a checklist based on the CONSORT statement and a different 2 review ers completed a st and ard template describing the outcomes used and the statistical significance of all reported treatment effects . Disagreements among review ers were resolved by consensus . The results showed that there were substantive deficiencies in the reporting of many of trial features , both related to method ological quality and completeness of reporting . Details on key features such as r and omization , double blinding , and the number of subjects lost to follow-up were reported in only 67 , 4 , and 62 % of trials , respectively . Reporting of r and om allocation to treatment group was associated with a lower proportion of positive treatments effects within trials , as was reporting of inclusion /exclusion criteria for study subjects , details on the intervention , animal signalment , significance tests of baseline differences for at least one variable , and the methods used to measure all outcomes . The results suggest that there are deficiencies in the current reporting of important features of RCTs conducted in livestock species and that these deficiencies may be associated with biased treatment effects . The creation and adoption of st and ards for trial reporting in livestock could aid authors , review ers , and editors in ensuring that necessary trial details are reported in all published trials Nitric oxide , a molecule produced in most mammalian cells , has bactericidal and virucidal properties . Nasal instillation of a nitric oxide releasing solution ( NORS ) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic , tilmicosin , for control of bovine respiratory disease ( BRD ) in cattle at low-to-moderate risk of developing BRD . The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD ( the target population for many BRD control programs ) . High-risk Angus-cross heifers ( n=840 ) were r and omly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control . Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups . The non-inferiority margin ( δ ) was set at 8.5 % . Thirty-six and 19 % of heifers were diagnosed with BRD in the NORS and tilmicosin groups , respectively . Because the lower bound of the 2-sided 95 % confidence interval ( CI ) of the difference in BRD prevalence between the 2 treatment groups ( 17 % ; 95 % CI=11 - 23 % ) was higher than δ , an inferiority of NORS was concluded . Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics , further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle OBJECTIVE To determine effects of vaccination prior to transit and prophylactic administration of florfenicol at time of arrival at a feedyard on health of cattle and colonization of the nasopharynx by Mannheimia haemolytica ( MH ) . ANIMALS 121 steers from Tennessee and 84 steers from New Mexico . PROCEDURE Half of the steers were vaccinated before transport to a feedyard . Steers from Tennessee were vaccinated with MH bacterin-toxoid , and steers from New Mexico were vaccinated intranasally with modified-live leukotoxin-deficient MH . Half of the vaccinates and nonvaccinates were r and omly selected to receive florfenicol on arrival at the feedyard . Steers were observed daily for respiratory tract disease ( RTD ) . RESULTS Administration of florfenicol at time of arrival reduced the incidence of RTD , delayed the interval before onset of RTD , and reduced the incidence of MH colonization of the nasopharynx for at least 4 days , but vaccination did not have any effect . Vaccination elicited an increase in serum antibody titers to MH . Administration of florfenicol at time of arrival reduced the development of serum antibody titers in intranasally vaccinated steers and both groups of nonvaccinated steers , but intranasal vaccination did not affect colonization by wild-type MH . CONCLUSIONS AND CLINICAL RELEVANCE Administration of florfenicol at time of arrival decreased the incidence of MH organisms in the nasopharynx and delayed the onset of RTD . Prophylactic use of suitable antibiotics is likely to reduce the incidence of acute RTD in calves for several days after arrival at feedyards , which is the period when they are most susceptible to infectious organisms Undifferentiated fever , or bovine respiratory disease complex ( BRDc ) , is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle , negatively impacting the cattle feedlot industry . Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc . Nitric oxide ( NO ) is a naturally occurring nano-molecule with a wide range of physiological attributes . This study evaluated the metaphylactic use of intranasal NO releasing spray ( NORS ) to control BRDc incidence in calves at low-moderate risk of developing BRDc , arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis . One thous and and eighty crossbred , multiple- source d , commingled , commercial , weaned beef calves were screened , enrolled , r and omized and treated upon arrival . Animals appearing sick were pulled ( from their pen ) by blinded pen keepers then assessed for BRDc symptoms ; blood sample s were taken for haptoglobin quantification and the animals were rescued with an antibiotic . After 35 days both groups showed no significant difference in BRDc incidence ( 5.2 % of animals from NORS group and 3.2 % from antibiotic group ) . Average daily weight gain of animals at day 150 for the NORS cohort was 1.17 kg compared to 1.18 kg for the antibiotic group ( p>0.05 ) . There was no significant difference in mortality in the first 35 days ( p=0.7552 ) , however , general mortality over 150 days trended higher in the antibiotic cohort . NORS treatment was shown to be safe , causing neither distress nor adverse effects on the animals . This large r and omized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment , as compared to conventional metaphylactic antibiotics , is non-inferior based on BRDc incidence and other metrics like weight and mortality . These data justify further studies in higher BRDc incidence risk population s to evaluate NORS as an alternative strategy to reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production Nitric oxide has bactericidal and virucidal properties . Nasal instillation of a nitric oxide releasing solution ( NORS ) on arrival at the feedlot was recently reported as inferior to a parenteral injection of tilmicosin ( macrolide antibiotic ) for control of bovine respiratory disease ( BRD ) in cattle at high-risk of developing BRD . We hypothesized that this inferiority was due to differences between treatments with regards to their effects on the nasopharyngeal microbiota . The objective was to compare nasal instillation of NORS versus parenteral administration of tilmicosin regarding their effects on the nasopharyngeal microbiota of feedlot cattle at high-risk of developing BRD . Culture-independent community profiling ( 16S rRNA sequencing ) and culture-based methods were used to evaluate treatment effects . High-risk Angus-cross heifers ( n=20 ) were r and omly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for prevention of BRD . Heifers were sample d using guarded deep nasal swabs immediately prior to treatment ( day 0 ) and on days 1 , 5 and 10 after treatment . Based on culture-independent community profiling , there was a distinct shift in composition of the nasopharyngeal microbiota during the first 10 d after arrival , with 116 OTUs changing over time , but no difference between treatment groups . However , culture-based methods detected a difference between treatment groups , with more cattle culture-positive for Pasteurellaceae in the NORS group at day 5 post-treatment . This difference in ability to inhibit colonization of the nasopharynx by Pasteurellaceae may be the basis for NORS being inferior to tilmicosin for control of BRD in high-risk cattle Three trials were conducted to evaluate the use of tilmicosin phosphate ( Micotil ) as a prophylactic medication for newly received , stressed beef cattle . In Trial 1 , 57 beef calves ( average initial BW = 170 kg ) were shipped to the research feedlot from Tennessee and either given no antibiotic at processing or treated with Micotil at 10 mg of tilmicosin phosphate/kg of BW . During a 28-d receiving period , treatment at processing with Micotil did not affect daily gain ( P < .17 ) or DMI ( P < .22 ) compared to control calves . Prophylactic treatment with Micotil decreased ( P < .01 ) the percentage of calves treated for symptoms of bovine respiratory disease from 46.4 to 0 % . In Trial 2 , 117 calves ( average initial BW = 191 kg ) were shipped from Tennessee and allotted r and omly to the same two treatments as in Trial 1 . All calves grazed a 24-ha pasture of irrigated winter wheat during the 28-d receiving period . Treatment of calves with Micotil at the time of arrival processing did not affect ( P > .50 ) daily gain during the trial ; however , as in Trial 1 , mass treatment with Micotil decreased ( P < .01 ) the percentage of calves treated for respiratory disease from 32.8 % to 12.1 % . In Trial 3 , two truckloads of beef calves ( 183 total ; average initial BW = 232 kg ) shipped from Tennessee were allotted r and omly to the same two treatments used in Trials 1 and 2 or to a third treatment that consisted of administration of Micotil at arrival processing if the rectal temperature of the calf was > or = 39.7 degrees C. ( ABSTRACT TRUNCATED AT 250 WORDS The objectives of this study were to 1 ) quantify effects of metaphylactic treatment for bovine respiratory disease ( BRD ) on growth performance , carcass characteristics , and lung lesion prevalence and severity ; 2 ) evaluate the association of lung lesion prevalence and severity with carcass characteristics ; and 3 ) evaluate effects of therapeutic treatment on carcass characteristics and lung lesion prevalence and severity . The study was conducted at a commercial feedlot in the Texas Panh and le in which steers ( n = 2,336 ) initially weighing 312.1 ± 9.6 kg were source d from auction markets and allocated in a r and omized complete block design to 1 of 3 treatments ( no metaphylactic [ no antimicrobial drug { ND } ] treatment , tilmicosin at 10 mg/kg BW [ TIL ] , and tulathromycin at 2.5 mg/kg BW [ TUL ] ) . Lungs of all steers were evaluated during harvest to assess presence and severity of pneumonic lesions in the anteroventral lobes and the presence and severity of pleural adherences . Compared to the ND treatment , steers treated via metaphylactic therapy had greater ( P < 0.05 ) metaphylactic cost , ADG , shrunk final BW , dressed carcass yield , HCW , 12th rib fat , calculated empty body fat ( EBF ) , and gross revenue , concurrent with reduced ( P < 0.05 ) BRD treatment costs and financial losses from BRD death and railed cattle , cumulatively result ing in greater financial returns . Lung lesions were present in 64.3 % of lungs and were distributed similarly between metaphylactic treatments ( 63.9 % ) and ND ( 65.1 % ) cattle . Steers with advanced lung lesions present at harvest were associated with reduced ( P < 0.05 ) HCW , KPH , 12th rib fat , calculated yield grade s , marbling scores , and calculated EBF as compared to steers without lung lesions . Steers pulled for BRD had increased ( P < 0.01 ) incidence of advanced lung lesions , mortality , and railers with decreased ( P < 0.05 ) HCW , 12th rib fat , KPH , marbling score , calculated EBF , and percentage choice carcasses when compared to non-BRD event steers . From the results of this study , controlling BRD through the use of metaphylactic treatments on arrival in heavier cattle improved financial returns primarily driven by reductions in cost of death loss and railers Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight ( BW ) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot . Ten thous and nine hundred and eighty-nine , recently weaned , auction market derived , crossbred beef steer and bull calves were r and omly allocated upon arrival at the feedlot to one of 2 experimental groups as follows : oxytetracycline , which received intramuscular long-acting oxytetracycline ( 300 mg/mL formulation ) at a rate of 30 mg/kg BW ; or tilmicosin , which received subcutaneous tilmicosin ( 300 mg/mL formulation ) at a rate of 10 mg/kg BW . There were 20 pens in each experimental group . In Study 1 and in the combined analysis , the initial undifferentiated fever ( UF ) treatment rate was significantly ( P < 0.05 ) higher in the oxytetracycline group as compared with the tilmicosin group . There were no significant ( P > or = 0.05 ) differences in first UF relapse , second UF relapse , third UF relapse , overall chronicity , overall rail , overall mortality , bovine respiratory disease ( BRD ) mortality , hemophilosis mortality , arthritis mortality , or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis . In addition , there were no significant ( P > or = 0.05 ) differences in initial weight , final weight , weight gain , days on feed , daily dry matter intake , average daily gain , or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses . In the economic analysis , there was a net economic advantage of $ 5.22 CDN per animal in the oxytetracycline group , due to a lower prophylactic cost , even though the UF therapeutic cost was higher Key Summary Points When r and omized trials have been done for several different treatment options for the same condition , it is important to underst and the pattern of all these comparisons . This pattern of comparisons is called the geometry of the treatment network . Existing indices can be used to measure the diversity and co-occurrence of treatments . These measures are the probability of interspecific encounter index and the co-occurrence score , respectively . An evaluation of 18 treatment networks for different conditions with 4 to 16 treatments each reveals distinct geometries in clinical evidence . The geometry of a treatment network may reflect both rational choices and various preference biases . Many diseases have several competing treatments ; however , clinical research , systematic review s , and meta-analyses have tended to focus on assessing the merits of 1 treatment at a time or , at most , the relative merits of 2 different regimens . This approach provides only a partial view of the possible wealth of treatment options for a given condition , without addressing the relative merits of all available options . The comparisons between different treatments constitute a network . Appropriate methodology has been developed for combining the data from a network of trials ( 14 ) , allowing the incorporation of evidence from all direct and indirect comparisons toward estimating summary treatment effects . We do not address the techniques here ; rather , we focus on the patterns ( geometry ) of direct comparisons within each network and what those patterns might mean . When examining a treatment network , some key questions need to be addressed . First , are there few or many treatments and , if many , are all treatments represented equally in the network or have some been disproportionately studied ? Second , are some pairs preferentially studied , whereas evidence is systematic ally lacking for some other comparisons ? In the terminology of the ecological sciences , these issues pertain to diversity and co-occurrence , respectively . We cumulatively call these properties the geometry of the network . A network 's geometry may reflect the wider clinical context of the evidence and may be shaped by rational choices for treatment comparators or by specific biases . In another study ( 2 ) , we preliminarily adapted metrics from the ecological literature to describe the diversity and co-occurrence features of treatment networks . Here , we extend and further operationalize these metrics by demonstrating how exploration of network geometry may help with interpretation of the evidence on multiple competing treatments for the same indication . Methods Network Geometry The diagram of all comparisons between treatments in a network can take many different shapes . At one extreme , the same comparator is used in all trials . This network resembles a star , with the common reference st and ard ( often placebo or no treatment ) in its center . At the other extreme , all treatments are compared with all others and no particular treatment or comparison is studied more often than the others . A wide range of intermediate situations is possible between these 2 extremes . Comparator Preference Bias Network geometry is determined by many parameters . Networks may vary in complexity from the simple ( such as a network in which only 3 treatment options exist ) to the very complex ( such as a network involving several dozens of treatments ) . Networks may also be asymmetric , meaning that certain treatments or comparisons are represented more heavily than others . Investigators ' preference for specific treatments may be dictated by various factors , including how long a treatment has been available for testing , the treatment 's perceived effectiveness and safety , how actively its development agenda has been pushed by its sponsors , and whether regulatory m and ates force or discourage its use ( 5 ) . When a treatment has been the reference st and ard for a long time , it may become widely accepted that investigators should always consider it as one of the compared options . Finally , what is studied is not necessarily what is eventually published : Selective reporting biases , publication bias , time lag bias , and other selection forces further affect the amount of publicly visible evidence on specific treatments ( 6 , 7 ) . Similar forces may also shape the relative amount of evidence for specific comparisons within the network . In addition , head-to-head comparisons between effective agents may be avoided in some fields ; the agents ' sponsors may not wish to risk an agent being declared inferior and losing its market share . Selecting straw man comparators may result in exaggerated treatment effects , particularly in industry-sponsored trials ( 810 ) . The extent of these various selection forces are expected to vary among networks . We cumulatively call these selection forces comparator preference bias . Evaluation of network geometry and the accompanying asymmetry may help address such bias . Underst and ing the underlying reasons requires careful examination of each network and knowledge of the field and the circumstances under which its evidence was accumulated . Data Sources and Selection We search ed PubMed through April 2007 by using the following algorithms : network AND meta- analysis , multiple treatment AND meta- analysis , indirect comparison AND meta- analysis , and indirect AND meta- analysis . We also search ed Thompson ISI Web of Knowledge for studies that cited method ological articles on multiple treatments meta- analysis ( 1 , 3 , 4 , 11 ) . We limited our search to English- language articles . We included meta-analyses of r and omized , controlled trials that involved at least 4 different treatments . The term treatment is used here to denote any kind of intervention ( medical , surgical , or other ) under any circumstances ( therapeutic or preventive ) , as well as no treatment or placebo . Where meta-analysts merged different schedules or doses of the same regimen or similar agents , we respected this merging . We excluded meta-analyses when their eligibility criteria excluded comparisons among treatments otherwise considered in the network . We did not consider the simplest networks of only 3 different treatments , because those have been extensively studied elsewhere ( 12 ) . Data Extraction One author extracted data about the main outcome and the condition studied ; the number of studies per comparison ; and , when available , the number of individuals per r and omized group . A second review er checked the extracted information . Statistical Analysis Diversity A network has less diversity when it contains fewer treatments . Among networks that contain the same number of treatments , a network has less diversity when the treatments are not equally represented ( some treatments are used more often than others ) . We use the probability of interspecific encounter ( PIE ) index , which is the probability that 2 r and omly sample d treatment groups from the network ( without replacement ) have been allocated to 2 different treatments . The PIE index is a continuous variable that decreases with increasing unevenness ; for operational purpose s , values of 0.75 or less can be considered to reflect limited diversity ( 13 ) . We also use the PIE index , which is the value of PIE divided by the maximum value that PIE can take for the given number of studies . The Appendix further discusses some properties of PIE and PIE . Co-occurrence Co-occurrence reflects whether particular pairwise comparisons of specific treatments are preferred or avoided . The number of checkerboard units shows how many times 2 treatments could have been compared , given their relative frequencies . The C-score reflects the overall average tendency of the treatments not to occur together . The statistical significance of the C-score is measured by using a permutations procedure . A P value less than 0.05 is considered to represent significant co-occurrence ; however , a more liberal threshold of less than 0.10 may also be used because the test tends to be underpowered with few trials ( 13 ) . We plotted the number of checkerboard units for each comparison in networks that showed significant co-occurrence . Visual inspection of the plot can reveal whether the apparent co-occurrence is due to a particular comparison that is highly avoided or to a small degree of selectiveness in many of the comparisons . All calculations were performed by using EcoSim software , version 7 ( 14 ) . Results Eligible Treatment Networks We retrieved 41 potentially eligible articles . Of those , 12 included fewer than 4 treatments , 8 excluded specific comparisons among otherwise eligible treatments , 1 did not form a network , 1 used some data for a method ological project but the network could not be reconstructed , and 1 used a subset of a network presented elsewhere . We included 18 eligible networks ( Figure 1 and Appendix Table 1 ) ( 3 , 1531 ) . Most of these networks were published very recently ( 2 in 1997 to 2000 , 5 in 2001 to 2004 , and 11 in 2005 to 2007 ) . With 1 exception ( 25 ) , all networks addressed effectiveness . Figure 1 . Eligible treatment networks . Shaded nodes indicate placebo or no active treatment . The thickness of the lines is proportional to the number of trials addressing each specific comparison . A. Star-shaped networks . B. Nonstar-shaped networks with limited diversity and significant co-occurrence . C. Nonstar-shaped networks with limited diversity and nonsignificant co-occurrence . D. Networks with considerable diversity and significant co-occurrence . E. Networks with considerable diversity and nonsignificant co-occurrence . ACE-i = angiotensin-converting enzyme inhibitor ; AES = actinomycin Deluting stents ; ARB = angiotensin-receptor blocker ; BMS = bare-metal stents ; CCB = calcium-channel blockers ; EES = everolimus-eluting stents ; GART = genotypic antiretroviral resistance testing ; ip = intraperitoneal ; MES = mycophenolate-eluting stents ; PART = phenotypic antiretroviral resistance testing ; PES = paclitaxel-eluting stents ; SES = OBJECTIVE To examine the effectiveness of mass medication with long acting antibiotics at feedlot entry on lot-fed Australian domestic cattle during a period of high risk for bovine respiratory disease ( BRD ) . DESIGN Systematic allocation at feedlot entry of tilmicosin , long acting oxytetracycline or no antibiotic treatment , to cattle lot fed for the Australian domestic market . Comparisons of growth rate , disease occurrence and mortality were made between the groups at the conclusion of the feeding period . RESULTS Cattle medicated with tilmicosin at 10 mg/kg body weight on entry to the feedlot grew 0.08 kg/d faster than cattle medicated with oxytetracycline at 20 mg/kg body weight and non-medicated cattle . There was no significant difference in growth rate between oxytetracycline medicated cattle and cattle not medicated with antibiotic at feedlot entry . Cattle medicated with tilmicosin at feedlot entry had 8 fewer cases of disease per 100 animals compared with cattle not medicated with antibiotic at feedlot entry . There was no significant difference in disease occurrence between oxytetracycline medicated cattle and those not medicated with antibiotic at feedlot entry . CONCLUSION Mass medication with tilmicosin at feedlot entry of cattle destined for the Australian domestic market may be used to reduce disease occurrence and increase growth rate during periods of high risk for BRD The efficacy of tulathromycin in decreasing the incidence of morbidity and mortality due to bovine respiratory disease ( BRD ) in 1,239 high-risk cattle was investigated at four US feedlots . Calves not exhibiting clinical signs of BRD received one of three treatments administered subcutaneously in the neck : physiologic saline at 0.02 ml/kg , tulathromycin at 2.5 mg/kg , or tilmicosin at 10 mg/kg . Each treatment group consisted of 413 calves . Calves with clinical signs of BRD and rectal temperatures of 104 degrees F or higher on days 1 through 14 were considered treatment failures ( BRD morbidity ) . Nasopharyngeal swabs from saline-treated morbidities were su bmi tted for isolation and identification of BRD organisms . Respiratory disease morbidity was highest in calves treated with saline and significantly ( P < or = .0001 ) lower in calves administered tulathromycin or tilmicosin . Morbidity from BRD was significantly ( P < or = .0001 ) higher in calves treated with tilmicosin than in calves treated with tulathromycin . Under conditions of this study , tulathromycin , given to calves at high risk of developing BRD , was significantly more effective in reducing BRD morbidity when compared to both saline- and tilmicosin-treated calves |
557 | 15,901,258 | For progesterone supplementation to be advocated for women at the risk of preterm birth , the prolongation of gestation demonstrated in this meta- analysis must translate into improved infant outcomes , including a reduction in mortality .
There is currently insufficient information to allow recommendations regarding the optimal dose , route , and timing of administration of progesterone supplementation | AIM The aim of this study is to assess the role of progesterone in preterm birth prevention . | 11 mg natural progesterone ( P ) was administered to 20 healthy menopausal women by means of a nasal spray or intramuscular injection . Circulating P levels were calculated at various times after administration . The spray formulation yielded a CMax of 3.75 ng/ml at TMax = 60 min , the area under the curve (AUC)0 - 720 being 1,481.6 + /- 343 . Intramuscular administration yielded a mean CMax of 4.137 ng/ml at TMax = 240 min , the AUC0 - 720 being 2,491.2 + /- 540 . P absorption was faster through the nasal than through the intramuscular route , but intramuscular administration led to high serum levels for a much longer period Progesterone was administered to postmenopausal women in a form of vaginal suppositories containing 100 and 200 mg active substance in Butyrum cacao ( BC ) and Massa estarinum ( ME ) , a base with emulsifying properties . In the case of single doses , blood sample s were taken at 2 , 4 , 6 , 24 , 48 and 72 h. Another group of patients received vaginal suppositories ( 100 mg progesterone ) once a day for a 6 day period , with blood sample s taken 12 h after each administration . The plasma levels of progesterone were evaluated by radioimmunoassay . The time of maximum concentration ( tmax ) was 4 h in most cases , and 6 h in the others . The plasma levels were not dose-proportional . Peak plasma concentrations were in the range of 10 - 15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 mg doses . The ratio of the mean area under the curve ( AUC ) for 200 mg and the mean AUC for the 100 mg dose was found to be 1.37 . Replacing BC with ME result ed in the lowering of cmax and AUC , and an increase in tmax following a reducing in the rate and extent of adsorption . In the case of ME suppositories , the variability in AUC , cmax and tmax was greater compared to that observed with the BC suppositories . Elimination half-time was in the range of 9 - 10 h for BC and 14 h for ME suppositories . In vitro assessment of the release kinetics from a hydrophobic and an emulsion type base confirmed previous findings : the latter base assured better pharmaceutical availability . The repeated doses did not seem to produce an accumulation of progesterone in the plasma . On the contrary , a small decrease in plasma levels over time appeared during the 6 day period . Numerical analysis revealed an excellent goodness of fit for the in vivo experimental data via biexponential curves , i.e. a pseudomonocompartmental model Whilst only about a third of all cerebral palsy occurs in children who had been of low birthweight , recent increases in the survival of low and very low birthweight infants have coincided with significant increases in the numbers of cerebral palsy children amongst them . This paper analyses data from the Western Australian Cerebral Palsy Register and from the Maternal and Child Health Research Data Base for stillbirths , neonatal deaths and survivors to address the issues of increased survival , cerebral palsy and timing of brain damage . The analysis is inconclusive but suggestive that both antenatal and postnatal complications are important in the increases in cerebral palsy in low birthweight infants . The good news is that this means that a certain proportion of postnatally damaged low birthweight survivors could possibly be prevented by better neonatal care . The bad news is that the remaining proportion have probably received their damage well before delivery and the possibilities for prevention are still remote . Further studies of low birthweight infants with cerebral palsy are urgently required . They should include antenatal factors , investigating the various aetiological pathways to preterm birth , r and omised controlled trials of neonatal interventions and search ing for better neonatal predictors of brain damage OBJECTIVE This study was undertaken to determine whether progestational agents can prevent inflammation-induced preterm parturition and fetal demise . STUDY DESIGN The activation of contractile and inflammatory pathways in response to localized intrauterine inflammation was investigated by using quantitative polymerase chain reaction ( PCR ) . Serum progesterone ( P4 ) levels and alterations in progesterone receptor-B ( PR-B ) were determined with radioimmunoassay and quantitative PCR , respectively . With our in vivo model of intrauterine inflammation , animals were r and omly assigned to pretreatment with P4 or medroxyprogesterone acetate ( MPA ) before intrauterine lipopolysaccharide ( LPS ) . Animals were observed for preterm delivery . The number of live pups 48 hours after intrauterine LPS was recorded for each treatment group . The ability of MPA to alter signal transduction pathways leading to preterm parturition were investigated by quantitative PCR and histochemical studies . RESULTS Intrauterine inflammation is associated with decreased serum progesterone levels and decreased transcription of PR-B. Preterm delivery rates were 100 % for LPS alone , 63 % for LPS+P4 , and 0 % for LPS+MPA . No live pups remained at 48 hours in the LPS or LPS+P4 groups . Pretreatment with MPA significantly preserved fetal viability . MPA suppressed activation of contraction-associated genes and inflammatory mediators and prevented cervical ripening in response to intrauterine inflammation . CONCLUSION MPA , with its progestational and anti-inflammatory properties , prevented inflammation-induced preterm parturition and significantly preserved fetal viability A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate . The present double-blind investigation was design ed to prospect ively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications . Three groups of active-duty women were studied , beginning between 16 and 20 weeks ' gestation . They were similar for parity , previous abortion , race , cigarette smoking , and marital status . Of these , 80 were given 17 alpha-hydroxyprogesterone caproate , 88 received placebo , and 78 declined to participate in the protocol . There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality . However , when comparison was made to a military dependent population , they had a significantly worse outcome with regard to both perinatal mortality ( p = 0.001 ) and infants with a birth weight less than 2,500 gm ( p = 0.01 ) . We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome , but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate OBJECTIVE The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population . STUDY DESIGN A r and omized , double-blind , placebo-controlled study included 142 high-risk singleton pregnancies . Progesterone ( 100 mg ) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes , between 24 and 34 weeks of gestation . Progesterone ( n = 72 ) and placebo ( n = 70 ) groups were compared for epidemiologic characteristics , uterine contraction frequency , and incidence of preterm birth . Data were compared by chi(2 ) analysis and Fisher exact test . RESULTS The preterm birth rate was 21.1 % ( 30/142 ) . Differences in uterine activity were found between the progesterone and placebo groups ( 23.6 % vs 54.3 % , respectively ; P < .05 ) and in preterm birth between progesterone and placebo ( 13.8 % vs 28.5 % , respectively ; P < .05 ) . More women were delivered before 34 weeks in the placebo group ( 18.5 % ) than in the progesterone group ( 2.7 % ) ( P < .05 ) . CONCLUSION Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity BACKGROUND The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF . METHODS Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used . All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test . The study group ( n = 150 ) withdrew vaginal progesterone from the day of positive HCG . The control group ( n = 153 ) continued administration of vaginal progesterone during the next 3 weeks of pregnancy . RESULTS The number of miscarriages prior to and after week 7 of gestation was seven ( 4.6 % ) and 15 ( 10.0 % ) in the study group and five ( 3.3 % ) and 13 ( 8.5 % ) in the control group respectively . The number of deliveries was 118 ( 78.7 % ) in the study group and 126 ( 82.4 % ) in the control group . The differences were not significant . CONCLUSIONS Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate , and thus no effect on the delivery rate . Progesterone supplementation can safely be withdrawn at the time of a positive HCG test Eighty pregnant women at high risk of giving birth prematurely were divided r and omly into two groups . Treatment with either 17 alpha-hydroxyprogesterone caproate , 250 mg by intramuscular injection once a week , or a placebo was given in a double-blind fashion . Imminent premature labor occurred in 29.0 % of the treated group and in 59.4 % of the control group ( p less than 0.025 ) . The rate of premature deliveries was also significantly lower in the treated group ( 16.1 % ) than in the control group ( 37.82 % ) ( p less than 0.05 ) . There were no cases of perinatal death or fetal malformations in either group . The mean birth weight of all infants of the treated group was significantly higher than in those of the control group ( 3111.9 + /- 905 gm versus 2680 + /- 813.4 gm , p less than 0.05 ) . The results support treatment with progesterone caproate for the prevention of premature labor We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients . Premature delivery did not occur in 18 patients receiving the progestational agent , whereas 41 per cent of the 22 receiving the palcebo had premature delivery ( P less than 0.01 ) . The mean duration of pregnancy and the mean birth weight in the former group ( 38.6 weeks + /- 1.6 S.D. , and 2836 g + /- 412 S.D. ) were both significantly greater ( P less than 0.025 ) than that in the latter ( 35.2 weeks + /- 6.7 S.D. ; 2361 g + /- 1085 S.D. ) . The perinatal mortality rate in the group given the progestational agent ( O per cent ) was significantly less than that observed in the placebo group ( 27 per cent ) ( P less than 0.05 ) . Although there were no complications attributable to the progestational drug , the study population was too small for assessment of immediate or long term safety . However , the results indicate a possible obstetric use for this drug The use of luteal phase support has been demonstrated in patients undergoing an IVF/ET procedure . This study was design ed to compare the absorption and the efficacy of two different luteal supports : 17-alpha-hydroxyprogesterone caproate ( Lentogest , AMSA , Italy ) and natural Progesterone ( Prontogest , AMSA , Italy ) . A total of 80 patients received luteal supplementation with 50 mg of natural P/day intramuscularly , until beta-hCG evaluation . Then , in case of positive beta-hCG , patients were r and omly divided into two groups ( A and B ) in order to compare two different protocol s : Group A , 17-OHPc ( 341 mg once a week ) and Group B , natural P ( 50 mg/day ) both intramuscularly and extended for 10 - 12 weeks . Our study showed that the treatment with 17-OHPc results in a higher percentage of pregnancy rate compared to natural P , but the differences are not statistically significant . Thus , we emphasize that 17-OHPc preparation for better acceptance appears to be the most suitable and comfortable method for luteal phase support OBJECTIVE To analyse hospital readmissions to 1 year in infants < 33 weeks ' gestation . STUDY DESIGN Cohort of very preterm infants born in Western Australia . METHODS Parental social class , history of asthma , race , gestational age , birthweight , sex , severity of respiratory disease and oxygen requirement at 28 days chronic lung disease ( CLD ) , 36 weeks and term , maternal smoking , cohabitation with siblings , breast-feeding duration and hospital readmissions were recorded prospect ively . RESULTS Data were available for 538 of 560 ( 96 % ) infants discharged . Eight died in the first year . Two hundred and twenty-five infants ( 42 % ) had 443 readmissions , of which 370 were medical and 73 surgical . Risk factors for medical readmission were Aboriginal race , male sex and CLD . Breast-feeding was protective . Risk factors for surgical admission were male sex , lower gestation , severe hyaline membrane disease , severe CLD and birthweight < 10th centile . CONCLUSIONS Readmission is common after very preterm birth . Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission |
558 | 25,626,481 | In people with platinum-sensitive disease , NMA found statistically significant benefits for PLDH plus platinum , and paclitaxel plus platinum for overall survival ( OS ) compared with platinum monotherapy .
PLDH plus platinum significantly prolonged progression-free survival ( PFS ) compared with paclitaxel plus platinum .
Of the non-platinum-based treatments , PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS , but not PFS , compared with topotecan monotherapy .
In people with platinum-resistant/-refractory ( PRR ) disease , NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS .
LIMITATIONS As platinum- and non-platinum-based treatments were evaluated separately , the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease .
CONCLUSIONS For platinum-sensitive disease , it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies .
For people with platinum-sensitive disease and treated with non-platinum-based therapies , it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £ 30,000 per additional QALY ; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH .
For patients with PRR disease , it is unlikely that topotecan would be considered cost-effective compared with PLDH . | BACKGROUND Ovarian cancer is the fifth most common cancer in the UK , and the fourth most common cause of cancer death .
Of those people successfully treated with first-line chemotherapy , 55 - 75 % will relapse within 2 years .
At this time , it is uncertain which chemotherapy regimen is more clinical ly effective and cost-effective for the treatment of recurrent , advanced ovarian cancer .
OBJECTIVES To determine the comparative clinical effectiveness and cost-effectiveness of topotecan ( Hycamtin ( ® ) , GlaxoSmithKline ) , pegylated liposomal doxorubicin hydrochloride ( PLDH ; Caelyx ( ® ) , Schering-Plough ) , paclitaxel ( Taxol ( ® ) , Bristol-Myers Squibb ) , trabectedin ( Yondelis ( ® ) , PharmaMar ) and gemcitabine ( Gemzar ( ® ) , Eli Lilly and Company ) for the treatment of advanced , recurrent ovarian cancer . | BACKGROUND Economic information is necessary for rational decision-making in health care . Many European countries require financial impact statements prior to drug approval , and many health care organizations in the USA consider cost-effectiveness when making formulary decisions . We report the findings and discuss the policy implication s of an economic evaluation based on an international , r and omized controlled trial of salvage therapy for epithelial ovarian cancer , wherein topotecan and pegylated liposomal doxorubicin ( PLD ) were found to have similar efficacy but differing toxicities . PATIENTS AND METHODS Direct costs to the payer were estimated for 235 North American and 239 European trial participants who had relapsed or failed platinum-based therapy . Unit costs were obtained from national sources or previously reported economic analyses . Sensitivity analyses were also performed . RESULTS Total cost per person in the topotecan arm was 12,325 dollars ( 95 % CI 9445 dollars to 15,415 dollars ; P > 0.05 ) higher in the USA-based analysis and 2909 dollars ( 95 % CI 779 dollars to 3415 dollars ; P < 0.05 ) higher in the UK-based analysis than for PLD . Pegylated liposomal doxorubicin was cost saving over a wide range of assumptions . The main differences ( per person ) in toxicity management following PLD compared with topotecan in Europe were for blood transfusions ( 1190 dollars versus 181 dollars , respectively ) and hospitalizations ( 1197 dollars versus 280 dollars , respectively ) . In North America , differences were mainly for granulocyte colony stimulating factors ( 1936 dollars versus 419 dollars micro g , respectively ) , erythropoietin ( 3493 dollars versus 308 dollars , respectively ) and blood transfusions ( 1346 dollars versus 140 dollars , respectively ) . CONCLUSIONS Policy makers who evaluate pharmacoeconomic studies should consider international differences in health care delivery . Cost assessment s based on information obtained from one country may not be relevant for policy makers in a different country BACKGROUND In the CALYPSO trial , carboplatin-pegylated liposomal doxorubicin ( CD ) demonstrated superior therapeutic index versus carboplatin-paclitaxel ( CP ) in patients with recurrent ovarian cancer . This paper reports the health-related quality of life ( HRQoL ) findings . MATERIAL S AND METHODS HRQoL was measured with the EORTC QoL-QC30 question naire and OV28 ovarian cancer module . Mean change scores from baseline in HRQoL subscales ( five functional scales and global health status ) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months . RESULTS Compliance was 90 % at baseline and 76 % , 64 % , 57 % at 3 , 6 , and 9 months , respectively . Baseline HRQoL showed already impaired global scores ( mean 62/100 ) and considerable symptom burden ( 90 % of patients reporting nonzero scores ) . Global QoL and abdominal symptom scores improved over time in both arms ; at 6 months , 36 % of patients met criteria for improved symptoms . Treatment with CD result ed in less peripheral neuropathy ( 9.8 versus 24.2 ) , fewer other chemotherapy side-effects ( 9.5 versus 16.2 ) , and less impact on body image ( 3.8 versus 10.4 ) versus CP ( all P<0.02 ) at 6 months . CONCLUSIONS These patient-reported outcomes confirm the overall lower toxicity of CD versus CP . The improved disease-related outcomes achieved with CD were not at the expense of BACKGROUND Cost-effectiveness/cost-utility analyses are increasingly needed to inform decisions about care . Algorithms have been developed using the Functional Assessment of Cancer Therapy ( FACT ) quality of life instrument to estimate utility weights for cost analyses . This study was design ed to compare these algorithms in the setting of ovarian cancer . METHODS GOG-0152 was a 550-patient r and omized phase III trial of interval cytoreduction , and GOG-0172 was a 415-patient r and omized phase III trial comparing intravenous versus intraperitoneal therapy among women with advanced ovarian cancer . QOL data were collected via the FACT at four time points in each study . Two published mapping algorithms ( Cheung and Dobrez ) and a linear transformation method were applied to these data . The agreement between measures was assessed by the concordance correlation coefficient ( r(CCC ) ) , and paired t-tests were used to compare means . RESULTS While agreement between the estimation algorithms was good ( ranged from 0.72 to 0.81 ) , there were statistically significant ( p<0.001 ) and clinical ly meaningful differences between the scores : mean scores were higher with Dobrez than with Cheung or the linear transformation method . Scores were also statistically significantly different ( p<0.001 ) between studies . CONCLUSIONS In the absence of prospect ively collected utility data , the use of mapping algorithms is feasible , however , the optimal algorithm is not clear . There were significant differences between studies , which highlight the need for validation of these algorithms in specific setting s. If cost analyses incorporate mapping algorithms to obtain utility estimates , investigators should take the variability into account BACKGROUND We have continued to monitor the survival of patients r and omised in a previously reported multicentre phase III study of topotecan versus paclitaxel in patients with advanced epithelial ovarian cancer who had failed one prior platinum-based regimen . PATIENTS AND METHODS Patients with bidimensionally measurable disease were r and omised to topotecan ( 1.5 mg/m(2)/day for 5 days ) or paclitaxel ( 175 mg/m(2)/day as a 3-h infusion ) every 21 days . Patients were eligible for treatment with the alternate therapy at third line . The European Organisation for Research and Treatment of Cancer Quality of Life ( EORTC QOL)-C30 question naire was also used to measure eight symptoms at baseline and during each course ( pain , anorexia , diarrhoea , fatigue , nausea and vomiting , dyspnea , constipation and insomnia ) . RESULTS A total of 226 patients were evaluable for response . Demographic characteristics were similar in both treatment groups , as were results of the EORTC QOL-30 question naire . For the topotecan group , median time to progression was 18.9 weeks ( range < 1 to 92.6 + weeks ; 25 % censored ) , and , for paclitaxel , 14.7 weeks ( range < 1 to 137.3 + weeks ; 12.3 % censored ) ; P = 0.076 . At 4 years post-r and omisation , median survival in the topotecan group was 63.0 weeks ( range < 1 to 238.4 + weeks ; 20.5 % censored ) and , for paclitaxel , 53.0 weeks ( range < 1 to 226.3 + weeks ; 12.3 % censored ) ; P = 0.44 . CONCLUSION Topotecan continues to demonstrate comparable efficacy and survival to paclitaxel with manageable and non-cumulative haematological toxicity . Non-haematological toxicity was generally mild for both groups . The long-term survival rate indicates substantial therapeutic benefit for this group of patients receiving topotecan at relapse of ovarian cancer BACKGROUND CALYPSO ( CAeLYx in Platinum Sensitive Ovarian ) patients compared carboplatin-pegylated liposomal doxorubicin ( C-PLD ) with carboplatin-paclitaxel ( C-P ) in patients with late-relapsing recurrent ovarian cancer ( ROC ) . We analyzed outcomes in patients ≥70 years . PATIENTS AND METHODS Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing > 6 months after first- or second-line platinum-based therapy were r and omly assigned to 4-weekly C area under the curve ( AUC ) 5 plus PLD 30 mg/m(2 ) or 3-weekly C AUC 5 plus P 175 mg/m(2 ) for six or more cycles . RESULTS One hundred and fifty-seven ( 16 % ) patients ≥70 years ( median : 74 years , C-PLD ; 73 years , C-P ; range 70 - 82 years ) were included ( n = 71 , C-PLD ; n = 86 , C-P ) . In comparing elderly and younger , elderly patients experienced fewer grade ≥2 allergic reactions ( P = 0.005 ) but more grade ≥2 sensory neuropathy ( P = 0.007 ) . Myelosuppression did not differ with age . Elderly patients completed planned treatment as frequently as younger ( 79 % , C-PLD ; 82 % , C-P ) . In comparing arms within elderly patients , C-P was associated with more grade ≥2 alopecia , sensory neuropathy , arthralgia/myalgia ( P < 0.001 for all ) , severe leukopenia plus febrile neutropenia ; C-PLD was associated with more grade ≥2 h and -foot syndrome ( P = 0.005 ) . Median progression-free survival was 11.6 months ( C-PLD ) and 10.3 months ( C-P ; P = 0.44 ) . CONCLUSIONS Patients ≥70 years experienced more neuropathy , with a higher incidence in the C-P arm . Similar to all study patients , C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P < .01 ) leading to early discontinuation ( 15 % v 6 % ; P < .001 ) occurred more frequently in the CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP BACKGROUND To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer ( ROC ) who received either CD [ carboplatin-pegylated liposomal doxorubicin ( PLD ) ] or CP ( carboplatin-paclitaxel ) in the CALYPSO trial . PATIENTS AND METHODS CALYPSO , an international phase III , non-inferiority trial , enrolled women with ROC that relapsed > 6 months following first- or second-line therapy . Patients were r and omized to CD or CP . Patients with a treatment-free interval of > 6 and ≤ 12 months were evaluated for progression-free survival ( PFS ) , the primary end point of CALYPSO trial , and safety . RESULTS A total of 344 partially platinum-sensitive patients were included ( N = 161 , CD and N = 183 , CP ) . The hazard ratio for PFS was 0.73 ( 95 % confidence interval : 0.58 - 0.90 ; P = 0.004 for superiority ) in favor of CD . Median PFS times were 9.4 months ( CD ) and 8.8 months ( CP ) . Toxicities more common with CP versus CD included grade 3/4 neutropenia ( 50 % versus 39 % ; P = 0.015 ) , grade 2 alopecia ( 86 % versus 9 % ; P < 0.001 ) , neuropathy and hypersensitivity reactions . H and -foot syndrome was more common with CD ; however , grade 3/4 reactions were low ( one patient in each arm ) . CONCLUSION Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients Background Platinum-based combinations are the st and ard second-line treatment for platinum-sensitive ovarian cancer ( OC ) . This r and omized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin ( LD ) with carboplatin and paclitaxel ( CP ) in this setting . Methods Patients with histologically confirmed recurrent OC , at the time of or more than 6 months after platinum-based chemotherapy , were r and omized to six cycles of CP ( carboplatin AUC5 + paclitaxel 175 mg/m2 , d1q21 ) or CLD ( carboplatin AUC5 + pegylated LD 45 mg/m2 , d1q28 ) . Results A total of 189 eligible patients ( CP 96 , CLD 93 ) , with a median age of 63 years , median Performance Status ( PS ) 0 and a median platinum free interval ( PFI ) of 16.5 months , entered the study . Discontinuation due to toxicity was higher in the CP patients ( 13.5 % versus 3 % , P = 0.016 ) . The overall response rate was similar : CP 58 % versus CLD 51 % , P = 0.309 ( Complete Response ; CR 34 % versus 23 % ) and there was no statistical difference in time-to-progression ( TTP ) or overall survival ( OS ; TTP 10.8 months CP versus 11.8 CLD , P = 0.904 ; OS 29.4 months CP versus 24.7 CLD , P = 0.454 ) . No toxic deaths were recorded . Neutropenia was the most commonly seen severe toxicity ( CP 30 % versus CLD 35 % ) . More frequent in CLD were severe thrombocytopenia ( 11 % versus 2 % , P = 0.016 ) , skin toxicity and Palmar-plantar erythrodysesthesia ( PPE ) grade 1 - 2 ( 38 % versus 9 % , P < 0.001 ) , while grade 3 neurotoxicity and alopecia were higher in CP ( 7 % versus 0 % , P = 0.029 , 20 % versus 5 % , P = 0.003 ) . PS and PFI were independent prognostic factors for TTP and OS . Conclusions The combination of pegylated LD with carboplatin is effective , showing less neurotoxicity and alopecia than paclitaxel-carboplatin . It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients .Trial Registration Australian New Zeal and Clinical Trials Registry : BACKGROUND Platinum rechallenge or weekly topotecan in combination have not been evaluated in r and omized trials for resistant recurrent ovarian cancer ( ROC ) . METHODS Patients with ROC after first- or second-line treatment including a platinum and taxane and progression within 6 months were r and omized to weekly paclitaxel ( wP , 80 mg/m(2)/week ) alone or in combination with carboplatin ( C , area under the curve of 5 mg/ml/min every 4 weeks ) or weekly topotecan ( wT , 3 mg/m(2)/week ) . Primary end point was progression-free survival ( PFS ) comparing wP and combination therapy . RESULTS Patients ( n = 165 ) received a median three cycles in each arm . Nonhematologic toxicity was not different , except increased hypersensitivity reactions with wP + C. Grade 3 - 4 hematologic toxic effects with wP , wP + C , and wP + wT , respectively , were neutropenia in 13 % , 54 % , and 42 % ; febrile neutropenia in 0 % , 4 % , and 5 % ; and anemia in 6 % , 19 % , and 29 % . Response rates were 35 % , 37 % , and 39 % , and median PFS times were 3.7 , 4.8 , and 5.4 months , respectively . PFS was not significantly different among the treatment arms [ hazard ratio ( HR ) 0.922 ; 95 % confidence interval ( CI ) 0.765 - 1.111 ; P = 0.46 ] or between monotherapy and combination therapy ( HR 0.951 ; 95 % CI 0.686 - 1.318 ; P = 0.76 ) . CONCLUSIONS Combination chemotherapy in platinum-resistant ROC was more toxic than weekly paclitaxel and did not significantly prolong PFS Abstract Objective : To assess the economic impact of two polychemotherapy regimens for patients with advanced ovarian cancer from the perspective of the Belgian health insurance and financing system . Design : An economic evaluation was integrated in an intergroup r and omised controlled trial ( EORTC 55931 ) in which patients were r and omised to receive the new treatment of paclitaxel and cisplatin or the st and ard therapy of cyclophosphamide and cisplatin . Data on the use of medical re sources were collected prospect ively for the 231 European Organization for Research and Treatment of Cancer ( EORTC ) patients in the trial and costs were valued by using unit prices . The outcome for the economic evaluation was mean survival time as determined by the so-called restricted means method , with the time point of restriction fixed by statistical criteria . A correction of censoring of the cost data collected in the trial was also performed . Main outcome measures and results : The paclitaxel and cisplatin group experienced a statistically significant improvement in mean survival time of 4 months , which was associated with an increase in the average total cost per patient of 6795 euros ( EUR ; 1998 values ) , when costs were assessed over the same period as the gain in mean survival time . This corresponds to a point estimate of the incremental cost-effectiveness ratio of EUR20 385 per life-year gained . The impact of uncertainty was assessed by using a bias-corrected and accelerated bootstrap method with 5000 re sample s , and the final results of the analysis are expressed in terms of a cost-effectiveness acceptability curve . Conclusions : The present economic evaluation has shown that the substitution of paclitaxel for cyclophosphamide in the chemotherapy regimen for women with advanced ovarian cancer leads to a significant improvement in patient survival , which is associated with an increase in costs for the Belgian health insurance system The ECOG Scale of Performance Status ( PS ) is widely used to quantify the functional status of cancer patients , and is an important factor determining prognosis in a number of malignant conditions . The PS describes the status of symptoms and functions with respect to ambulatory status and need for care . PS 0 means normal activity , PS 1 means some symptoms , but still near fully ambulatory , PS 2 means less than 50 % , and PS 3 means more than 50 % of daytime in bed , while PS 4 means completely bedridden . An inter-observer variability study of PS assessment has been carried out to evaluate the non-chance agreement among three oncologists rating 100 consecutive cancer patients . Total unanimity was observed in 40 cases , unanimity between two observers in 53 cases , and total disagreement in seven cases . Kappa statistics reveal the ability of the observers compared to change alone and were used to evaluate non-chance agreement . Overall Kappa was 0.44 , ( 95 % confidence limits 0.38 - 0.51 ) . The Kappa for PS 0 was 0.55 ( 0.44 - 0.67 ) , while those for PS 1 , 2 , 3 and four were 0.48 ( 0.37 - 0.60 ) , 0.31 ( 0.19 - 0.42 ) , 0.43 ( 0.32 - 0.55 ) , and 0.33 ( 0.33 - 0.45 ) , respectively . If one observer allocated patients to PS 0 - 2 , then another r and omly selected observed placed the patients in the same category with a probability of 0.92 . For patients with PS 3 - 4 the probability that the same category would be chosen was 0.82 . Overall , the non-chance agreement between observers was only moderate , when all ECOG Performance Status groups were considered . However , agreement with regard to allocation of patients to PS 0 - 2 versus 3 - 4 was high . This is of interest because this cut-off is often used in clinical studies Background : OVA-301 is a large r and omized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin ( PLD ) over PLD alone in relapsed ovarian cancer . The optimal management of patients with partially platinum-sensitive relapse [ 6–12 months platinum-free interval ( PFI ) ] is unclear . Patients and methods : Within OVA-301 , we therefore now report on the outcomes for the 214 cases in this subgroup . Results : Trabectedin/PLD result ed in a 35 % risk reduction of disease progression ( DP ) or death [ hazard ratio ( HR ) = 0.65 , 95 % confidence interval ( CI ) , 0.45–0.92 ; P = 0.0152 ; median progression-free survival ( PFS ) 7.4 versus 5.5 months ] , and a significant 41 % decrease in the risk of death ( HR = 0.59 ; 95 % CI , 0.43–0.82 ; P = 0.0015 ; median survival 23.0 versus 17.1 months ) . The safety of trabectedin/PLD in this subset mimicked that of the overall population . Similar proportions of patients received subsequent therapy in each arm ( 76 % versus 77 % ) , although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum ( 49 % versus 55 % ) . Importantly , patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum ( HR = 0.63 ; P = 0.0357 ; median 13.3 versus 9.8 months ) . Conclusion : This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease ( PFI 6–12 months ) OBJECTIVE Trabectedin in combination with PLD improves progression-free survival ( PFS ) and overall response rate ( ORR ) in comparison to PLD alone in patients with relapsed ovarian cancer ( J Clin Oncol ; 2010 28:3107 - 14 ) . Here we report the impact of the treatment combination on patient-reported functional status and symptoms . METHODS Patient-reported outcome ( PRO ) question naires , EORTC-QLQ C30 , OV28 , and EQ-5D were completed by patients at screening and on Day 1 of every other treatment cycle starting with Cycle 1 , and at the end-of-treatment visit . RESULTS Of the 672 patients r and omized in this study , 663 treated patients completed at least one of the baseline question naires . Median cycles of treatment was 6 ( 131 days ) for the combination arm and 5 ( 143 days ) for the monotherapy arm . Longitudinal data analyses showed no significant differences between the treatment arms for any of the pre-specified scales . Similar analyses of other scales , including Health Index scores and Health State on the Visual Analog Scale , support these findings . Start of subsequent therapy was significantly delayed in the combination arm compared with the monotherapy arm ( p=0.0032 ) . CONCLUSIONS The addition of trabectedin to PLD led to little or no decrement in patient-reported functional status and symptoms in patients with relapsed ovarian cancer , as compared to treatment with PLD alone . The combination led to manageable and non-cumulative overall toxicity with a fewer PLD-associated adverse events , and a significant improvement in PFS and ORR compared to single agent PURPOSE To compare the efficacy and safety of pegylated liposomal doxorubicin ( PLD ) and topotecan in patients with epithelial ovarian carcinoma that recurred after or did n't respond to first-line , platinum-based chemotherapy . PATIENTS AND METHODS Patients with measurable and assessable disease were r and omized to receive either PLD 50 mg/m(2 ) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks . Patients were stratified prospect ively for platinum sensitivity and for the presence or absence of bulky disease . RESULTS A total of 474 patients were treated ( 239 PLD and 235 topotecan ) . They comprised the intent-to-treat population . The overall progression-free survival rates were similar between the two arms ( P = .095 ) . The overall response rates for PLD and topotecan were 19.7 % and 17.0 % , respectively ( P = .390 ) . Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan . Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival ( P = .037 ) , with medians of 28.9 for PLD versus 23.3 weeks for topotecan . For overall survival , PLD was significantly superior to topotecan ( P = .008 ) , with a median of 108 weeks versus 71.1 weeks . The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan ( P = .455 ) . Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification , or growth factor or blood product utilization . CONCLUSION The comparable efficacy , favorable safety profile , and convenient dosing support the role of PLD as a valuable treatment option in this patient population The study consisted of a cost-minimisation analysis since the findings from a multicentre r and omised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan . An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen . The cost evaluation included direct medical costs : drug , drug administration and costs of managing adverse events . Estimation of re sources used in managing adverse events was made retrospectively through an expert panel . Results obtained per patient were : cost of drug and administration , 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan , while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan . The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan , showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan . Sensitivity analyses verified the robustness of the results . These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen Background : OVA-301 is a large r and omized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin ( PLD ; CentoCor Ortho Biotech Products L.P. , Raritan , NJ , USA ) . over single-agent PLD in 672 patients with relapsed ovarian cancer , particularly in the partially platinum-sensitive subgroup [ platinum-free interval ( PFI ) of 6–12 months ] . This superiority has been suggested to be due to the differential impact of subsequent ( platinum ) therapy . Patients and methods : A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted . Results : Similar proportions of patients received subsequent therapy in each arm ( 76 % versus 77 % ) , including further platinum-based regimens ( 49 % versus 55 % ) . Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time ( median delay 2.5 months versus PLD arm ) . Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset ( hazard ratio = 0.63 ; P = 0.0357 ) . Conclusion : The superiority of trabectedin/PLD over single-agent PLD in OVA-301 can not be explained by differences in the extent or nature of subsequent therapies administered to these patients . On the other h and , these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum OBJECTIVE Compared with every-3-week paclitaxel ( q3 T ) plus carboplatin , dose-dense weekly paclitaxel ( ddT ) plus carboplatin improved the survival of ovarian cancer patients . We performed a cost analysis comparing these two regimens . METHODS Using a Markov decision model , an acceptable incremental cost-effectiveness ratio ( ICER ) per progression-free life-year saved ( PFLYS ) was estimated . Cost of drugs , growth colony-stimulating factors , and transfusions were derived from Medicare reimbursement data . Survival and rates of complications were estimated based on the clinical trial . RESULTS Using a body weight and surface area of an average woman age 63 , the estimated cost per cycle of ddT was $ 107 vs. $ 80 for q3 T . The costs per cycle of combination chemotherapy including treatment administration were $ 873 for ddT and $ 535 for q3 T . With a median progression-free survival ( PFS ) of 28 months with ddT vs. 17.2 months with q3 T , the ICER was $ 5809 per PFLYS for ddT compared with q3 T arm . Using a maximum ICER of $ 100,000 per LYS as cost-effective threshold , the ddT regimen was cost-effective . The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens . A 4-month difference in PFS result ed in a $ 1200 change of ICER per PFLYS . The ICER was also sensitive to overall survival difference , rate of hematological toxicity , and rate of discontinuation . CONCLUSIONS In this economic model , dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer PURPOSE Weekly administration of topotecan ( Tw ) is less toxic and widely considered a better treatment option than conventional 5-day therapy ( Tc ) in women with platinum-resistant recurrent ovarian cancer . We conducted a r and omized phase II trial ( TOWER [ Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer ] ) to better define the ratio between benefits and risks with either treatment approach . PATIENTS AND METHODS Patients were r and omly assigned to two independent two-stage protocol s of Tw ( 4 mg/m(2)/wk administered on days 1 , 8 , and 15 ) or Tc ( 1.25 mg/m(2)/d on days 1 to 5 ) . We evaluated risk ratios ( RRs ) for the primary end point of clinical benefit ( complete response , partial response , and stable disease ) , the duration of progression-free survival ( PFS ) and overall survival ( OS ) , associated hazard ratios ( HRs ) , and RRs of toxicity with 95 % CIs . RESULTS In total , 194 patients were r and omly assigned at 54 centers to Tw ( n = 97 ) or Tc ( n = 97 ) . Clinical benefit was observed in 36 of 76 ( 47 % ; 95 % CI , 36 % to 59 % ) Tw and 46 of 80 ( 58 % ; 95 % CI , 46 % to 68 % ) Tc patients ( RR , 1.21 ; 95 % CI , 0.90 to 1.64 ; P = .205 ) . Patients in the Tw group had a slightly shorter PFS ( HR , 1.29 ; 95 % CI , 0.96 to 1.76 ) but similar OS ( HR , 1.04 ; 95 % CI , 0.74 to 1.45 ) compared with Tc . Tw was associated with significantly lower risks of anemia ( RR , 0.35 ; 95 % CI , 0.16 to 0.79 ) , neutropenia ( RR , 0.38 ; 95 % CI , 0.23 to 0.65 ) , and thrombocytopenia ( RR , 0.23 ; 95 % CI , 0.09 to 0.57 ) . CONCLUSION With regard to effectiveness in terms of response and PFS , Tc remains the st and ard of care in patients with platinum-resistant recurrent ovarian cancer . However , comparable OS rates and a favorable toxicity profile make Tw another viable treatment option in this setting INTRODUCTION Paclitaxel plus cisplatin is considered to be the st and ard first-line therapy for advanced ovarian cancer . Previous to this study , economic data on this combination result ed from r and omised clinical trials ( RCTs ) . Therefore , the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin ( PC ) and cyclophosphamide-cisplatin ( CC ) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital . METHOD A retrospective cost-effectiveness analysis , from the hospital-payer perspective , was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics ( FIGO ) stage II , III or IV ovarian cancer treated between 1995 and 2000 . Median overall survival ( OS ) was used as the primary endpoint . The quality -adjusted time was assessed by the quality -adjusted time without symptoms or toxicity ( Q-TWiST ) method . Direct medical costs were collected for each patient . Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of USD 1 = 7 French francs . Several univariate sensitivity analyses were carried out varying unit costs , medical practice s and administration of paclitaxel . RESULTS The incremental cost of the PC regimen was USD 10,716 per patient . OS and quality -adjusted time were improved by 10.8 and 9.3 months with the PC regimen . The cost per life-year gained and per added QALY were USD 11,907 and USD 13,827 , respectively . The robustness of the results was confirmed in sensitivity analyses . CONCLUSION Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting . We reported higher incremental costs and lower clinical benefits than RCT -based findings , suggesting that RCT -based findings were clearly balanced by our pragmatic approach based on clinical practice s. Observational studies can provide complementary and balanced data for decision making PURPOSE A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated . Retrospectively , we determined whether the use of this CA-125 definition in a r and omized trial would have shown the same magnitude of difference between the treatment arms as was shown when the st and ard progression definition was used . PATIENTS AND METHODS A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma , of whom 628 were assessable according to CA-125 . The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125 . RESULTS Of the 628 patients assessable for both definitions , 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition . There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm ( TP ) compared with the cyclophosphamide and cisplatin arm ( CP ) when either st and ard or CA-125 criteria were used to define progression ( st and ard , P = .002 ; CA-125 , P = .011 ) . The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression . CONCLUSION The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or st and ard criteria were used to define progression PURPOSE This was a multicentric , open , r and omized , phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life , time to progression , and survival . PATIENTS AND METHODS Eighty-six patients with platinum-pretreated advanced ovarian cancer were r and omly assigned to two arms : 41 received paclitaxel at 175 mg/m(2 ) over 3 hours every 3 weeks , and 45 received oxaliplatin at 130 mg/m(2 ) over 2 hours every 3 weeks . For inclusion , patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and /or carboplatin-containing chemotherapy regimens within the last 12 months . RESULTS Seven confirmed responses were observed in each arm , for an overall response rate in the total treated population of 17 % ( 95 % confidence interval [ CI ] , 7 % to 32 % ) in the paclitaxel arm and 16 % ( 95 % CI , 7 % to 29 % ) in the oxaliplatin arm . Median time to progression was 14 weeks and 12 weeks , and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms , respectively . Among 63 patients with a 0- to 6-month progression-free , platinum-free interval , there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients . Nine patients ( 22 % ) in the paclitaxel arm had grade 3 or 4 neutropenia ( National Cancer Institute of Canada [ NCIC ] Common Toxicity Criteria ) . Two patients ( 4 % ) experienced grade 3 thrombocytopenia in the oxaliplatin arm . Maximum grade ( grade 3 ) NCIC neurosensory toxicity was experienced by three patients ( 7 % ) in the paclitaxel arm and by four patients ( 9 % ) in the oxaliplatin arm . CONCLUSION Single-agent oxaliplatin at 130 mg/m(2 ) every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer OBJECTIVE Because debate continues over the role of combination , platinum-based chemotherapy for platinum-sensitive ( PS ) , recurrent ovarian cancer ( OC ) , we compared overall survival ( OS ) , progression-free survival ( PFS ) , confirmed complete response rate and time to treatment failure in this population . METHODS Patients with recurrent stage III or IV OC , a progression-free and platinum-free interval of 6 - 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible . Patients were r and omized to i.v . pegylated liposomal doxorubicin ( PLD ) ( 30 mg/m2 ) plus i.v . carboplatin ( AUC=5 mg/mL min ) once every 4 weeks ( PLD arm ) or i.v . carboplatin alone ( AUC=5 mg/mL min ) once every 4 weeks . RESULTS The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned . Response rates were 67 % for the PLD arm and 32 % for the carboplatin only arm ( Fisher 's exact p=0.02 ) . The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone . The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm ( p=0.02 ) . Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities , all hematological in nature . CONCLUSION This study was closed early because of slow patient accrual . The response rate , median PFS and OS results are intriguing . These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS , recurrent OC . The regimen should be further tested In a r and omized controlled trial ( RCT ) of patients with recurrent , platinum‐sensitive ovarian cancer , the combination weekly docetaxel and carboplatin was associated a with progression‐free survival ( PFS ) of 13.7 months compared with 8.4 months for sequential , single‐agent docetaxel followed by carboplatin . The objective of the current study was to construct a cost‐utility model to compare these 2 regimens with the incorporation of prospect ively collected quality ‐of‐life ( QoL ) data BACKGROUND The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma . PATIENTS AND METHODS Patients with recurrent ovarian carcinoma , 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines , were r and omized to receive carboplatin area under the curve ( AUC ) 5 ( arm A ) or paclitaxel 175 mg/m(2 ) + carboplatin AUC 5 ( arm B ) . The primary end point was objective response , following a ' pick up the winner ' design . Secondary end points included time to progression ( TTP ) , overall survival , tolerability and quality of life ( QoL ) . RESULTS Eighty-one patients were r and omized and included in the intention-to-treat analysis . The response rate in arm B was 75.6 % [ 26.8 % complete response ( CR ) + 48.8 % partial response ( PR ) ] [ 95 % confidence interval ( CI ) 59.7 % to 87.6 % ] and 50 % in arm A ( 20 % CR + 30 % PR ) ( 95 % CI 33.8 % to 66.2 % ) . No significant differences were observed in grade 3 - 4 hematological toxicity . Conversely , mucositis , myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B ( 95 % CI 36.9 - 61.3 ) and 33.7 weeks in arm A ( 95 % CI 25.8 - 41.5 ) . No significant differences were found in the QoL analysis . CONCLUSIONS Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma PURPOSE To determine if increasing the dose of paclitaxel increases the probability of clinical response , progression-free survival , or overall survival in women who have persistent or recurrent ovarian cancer , and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever . PATIENTS AND METHODS Consenting patients with persistent , recurrent , or progressing ovarian cancer , despite first-line platinum therapy ( but no prior taxane ) , were r and omly assigned to paclitaxel 135 mg/m2 , 175 mg/m2 , or 250 mg/m2 over 24 hours every 3 weeks . Patients receiving paclitaxel 250 mg/m2 were also r and omly assigned to 5 or 10 microg/kg of filgrastim per day subcutaneously . RESULTS Accession to the paclitaxel 135-mg/m2 arm was closed early . Among the 271 patients on the other regimens with measurable disease , partial and complete response on paclitaxel 250 mg/m2 ( 36 % ) was significantly higher than on 175 mg/m2 ( 27 % , P = .027 ) . This difference was more evident among patients who never responded to prior platinum . However , progression-free and overall survival results were similar . The median duration s of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250 mg/m2 , respectively . Thrombocytopenia , neuropathy , and myalgia were greater with paclitaxel 250 mg/m2 ( P < .05 ) . The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m2 was 19 % and 18 % on the 5-microg/kg and 10-microg/kg filgrastim dose , respectively ( 22 % for paclitaxel 175 mg/m2 without filgrastim ) . CONCLUSION Paclitaxel exhibits a dose effect with regard to response rate , but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2 plus filgrastim . Doubling the filgrastim dose from 5 to 10 microg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B ) following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) protocol s # 178 and # 218 . Arm 1 is 6 cycles of CP . Arm 2 is 6 cycles of CP followed by 12 cycles of P ( CP+P ) . Arm 3 is 1 cycle of CP , 5 cycles of CPB , and 16 cycles of B ( CPB+B ) . Parameters include PFS , overall survival ( OS ) , cost , complications ( neuropathy for P and bowel perforation for B ) , and quality -of-life utility values . Sensitivity analyses were performed . RESULTS The incremental cost-effectiveness ratio ( ICER ) for CT+T is $ 13,402/ quality adjusted life year ( QALY ) gained compared to CP . For CPB+B compared to CP , the ICER is $ 326,530/QALY . When compared simultaneously , CPB+B is dominated , i.e. is more costly and less effective than CP+P. Results were robust to parameter variation . At a willingness to pay threshold of $ 100,000/QALY , CP+P was the preferred option throughout most of the decision space . Sensitivity analyses suggest that CPB+B would become the preferred option if it were to improve OS by 6.1 years over CP+P. CONCLUSIONS In this model , B consolidation for advanced EOC was associated with a modest improvement in effectiveness that is less than that with P consolidation and more costly . A statistically significant improvement in survival may improve the value of B consolidation OBJECTIVES R and omized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin ( PLD ) in recurrent ovarian cancer , and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent . METHODS To further examine both of these clinical ly-relevant issues , the survival outcome ( with longer follow-up ) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin ( AUC 5 ) to carboplatin ( AUC 5 ) plus PLD ( 30 mg/m(2 ) ) delivered on an every 4-week schedule in recurrent ovarian cancer ( SWOG 0200 ) were re-analyzed . RESULTS In the limited number of patients ( n=61 ) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual , there was an initially reported improvement in outcome associated with the combination regimen . With longer follow-up and additional events there is still a statistically-significant improved progression-free survival ( median : 12 versus 8 months , p=0.02 ) , but the previously observed impact of the two-drug regimen on overall survival is no longer apparent ( median : 31 versus 18 months ; p=0.2 ) . While no hypersensitivity reactions were reported in the carboplatin plus PLD arm ( 0/31 ) , 9 of 30 patients ( 30 % ) of women r and omized to single agent carboplatin experienced an allergic episode ( p=0.0008 ) , with 5 being > grade 2 in severity . CONCLUSION Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial , the effect on overall survival is not statistically significant . For currently unknown reasons , administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions For disease indications such as Acquired Immune Deficiency Syndrome ( AIDS ) and various cancers , r and omization to a pure control treatment may be scientifically desirable but not ethically acceptable . Clinicians may insist that the experimental treatment be made available , at least as a rescue medication , for all patients in the control arm . A method for estimating a treatment effect in survival data from r and omized clinical trials of this type is developed under an accelerated failure time model . This approach retains all patients in the groups to which they were r and omized and is not based on an ad hoc subgroup analysis . By conditioning on having observed patient switch times , this method avoids the need to model patient switching patterns in the analysis . This new approach is evaluated using simulation studies , and is illustrated through analysing data from a Medical Research Council lung cancer trial OBJECTIVE We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent platinum-sensitive ovarian cancer . METHODS A Markov decision tree was constructed comparing three chemotherapy regimens : ( 1 ) carboplatin alone ( C ) ; ( 2 ) paclitaxel/carboplatin ( PC ) ; ( 3 ) gemcitabine/carboplatin ( GC ) . Progression-free survival ( PFS ) and adverse event rates were estimated from published r and omized controlled trials ( RCTs ) . Costs of treatment and adverse events were obtained using Medicare reimbursement data . RESULTS Estimated mean and median progression-free survival were 8.0 and 6.0 months for C , 10.1 and 7.8 months for PC , 10.5 and 8.4 months for GC , respectively . C was the least expensive strategy , costing $ 501 per progression-free month ( PFM ) . PC had an incremental cost-effectiveness ratio ( ICER ) of $ 1297 per additional PFM ( $ 15,564 per additional progression-free year ( PFY ) ) compared to C. GC had an ICER of $ 23,199 per additional PFM ( $ 278,388 per additional PFY ) compared to PC . Results were insensitive to variation in the rates and costs of toxicities over clinical ly reasonable ranges . The model was sensitive to changes in PFS estimates . When the PFS of GC was assumed to be equivalent to that of PC , GC was strongly dominated ( more expensive and no more effective ) by PC due to the additional costs . Adjustment for neurotoxicity-associated quality of life ( QoL ) did not change rankings of strategies . CONCLUSIONS PC appears to be relatively cost-effective compared to C for the treatment of recurrent platinum-sensitive ovarian cancer . GC appears to be less cost-effective compared to PC , with an ICER ten times higher PURPOSE To assess the activity , efficacy , and tolerability of single-agent paclitaxel and a platinum-containing regimen in previously treated patients with recurrent ovarian cancer . PATIENTS AND METHODS Patients who achieved complete remission with platinum-based regimens and whose disease recurred after a progression-free interval of more than 12 months were included in the study . Every 21 days , patients received paclitaxel 175 mg/m(2 ) intravenously ( IV ) over 3 hours or cyclophosphamide 500 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , and cisplatin 50 mg/m(2 ) ( CAP ) IV . RESULTS Between June 1992 and May 1995 , 97 consecutive patients with assessable or measurable disease were r and omized to paclitaxel ( n = 50 ) or CAP ( n = 47 ) . The median number of cycles on each arm was six . Toxicities included grade 3/4 leukopenia ( 4 % for paclitaxel v 34 % for CAP ) , grade 3/4 neutropenia ( 13 % v 36 % ) , grade 1/2 myalgia ( 19 % v 4 % ) , allergic reactions ( 15 % v 2 % ) , and grade 2/3 nausea and vomiting ( 17 % v 51 % ) . Complete responses were achieved in 17 % and 30 % of patients receiving paclitaxel and CAP , respectively , and partial responses were achieved in 28 % and 25 % , respectively ( P = .062 ) . At a median follow-up time of 49 months , median progression-free intervals were 9 months for paclitaxel and 15.7 months for CAP ( Cox analysis : hazards ratio [ HR ] , 0.60 ; 95 % confidence interval [ CI ] , 0.37 to 0.97 ; P = .038 ) ; median overall survival times were 25.8 months for paclitaxel and 34.7 months for CAP ( Cox analysis : HR , 0.58 ; 95 % CI , 0.34 to 0.98 ; P = .043 ) . CONCLUSION Rechallenge with either single-agent paclitaxel or platinum-based chemotherapy is effective in this patient population . Preliminary results suggest that single-agent paclitaxel may not be as active as platinum-based chemotherapy in recurrent ovarian cancer . Larger r and omized trials are needed The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly ( arm A ) or every 3 weeks ( arm B ) , and to assess the safety of intravenous steroids versus st and ard peroral premedication . Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were r and omized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks . The median delivered dose intensity was 77.6 mg/m 2 /week in the weekly arm , and 72.7 mg/m 2 /week in the every 3 weeks arm . WHO grade 3 - 4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity , response rate , time to progression or survival between arms was observed . Weekly paclitaxel at a dose of 67 mg/m 2 /week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks . Intravenous steroids are a safe alternative to oral steroids OBJECTIVE Provide long-term follow-up data for women treated in a r and omized multicenter study of pegylated liposomal doxorubicin compared with topotecan . METHODS Patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy were r and omized to receive pegylated liposomal doxorubicin 50 mg/m(2 ) every 28 days ( n = 239 ) or topotecan 1.5 mg/m(2 ) per day for 5 days every 21 days ( n = 235 ) . Patients were stratified prospect ively based on response to initial platinum-based chemotherapy as well as the presence or absence of bulky disease . Most patients had been previously treated with platinum and taxanes ( 74 % in the pegylated liposomal doxorubicin group and 72 % in the topotecan group ) . Survival data are mature : 87 % of patients have died ( n = 413 ) . RESULTS There was an 18 % reduction in the risk of death for patients treated with pegylated liposomal doxorubicin ( median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients ; HR = 1.216 ; 95 % confidence interval ( CI ) 1.000 - 1.478 ; P = 0.050 ) . The hazard ratio for all r and omized subjects ( includes those r and omized , but never treated ; n = 481 ) was 1.23 ( median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients ; 95 % CI 1.01 - 1.50 ; P = 0.038 ) . For patients with platinum-sensitive disease , there was a 30 % reduction in the risk of death for the pegylated liposomal doxorubicin-treated group ( median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients ; HR = 1.432 ; 95 % CI 1.066 - 1.923 ; P = 0.017 ) . In patients with platinum-refractory disease , survival was similar between treatment groups . CONCLUSION Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer . The survival benefit is pronounced in patients with platinum-sensitive disease OBJECTIVE To evaluate the cost-effectiveness of tertiary referral care for ovarian cancer patients in the Netherl and s. METHODS We collected clinical and registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996 - 2003 in a r and om sample of Dutch hospitals . Decision modelling was used to compare the cost-effectiveness of treatment in general hospitals , semi-specialized hospitals , and tertiary care centers . The actual direct medical costs of ovarian cancer treatment were evaluated . Long-term outcomes in terms of costs , quality -adjusted life-years ( QALYs ) , and incremental costs per QALY gained were estimated . To assess uncertainty , multivariable sensitivity analyses and scenario analyses were performed . RESULTS Treatment of ovarian cancer patients in semi-specialized hospitals costs on average euro882 more than in general hospitals ( 95 % confidence interval -720 to 2462 ) and yields 0.12 additional QALYs ( 95 % CI 0.02 to 0.22 ) , result ing in an incremental cost-effectiveness ratio ( ICER ) of euro7135 . Patients treated in tertiary care centers incurred again higher costs ( euro10,591 , 95 % CI 8757 to 12,480 ) and also higher QALYs ( 0.10 , 95 % CI 0 to 0.21 ) , result ing in an ICER of euro102,642 compared to semi-specialized hospitals . If the optimal debulking rate in tertiary care centers would increase to 70 % , costs could drop below euro30,000 per QALY . CONCLUSION Current treatment of ovarian cancer patients in semi-specialized hospital setting s is a cost-effective strategy , while treatment in tertiary care centers becomes only cost-effective when better surgical results would be achieved BACKGROUND There is a need to delineate how the best available serum marker for ovarian cancer , CA 125 should be used in monitoring the treatment of individual patients , and in clinical trials . PATIENTS AND METHODS The situations where measurement of CA 125 could alter the management of individual patients during therapy and at relapse were critically analysed . Precise definitions for response according to CA 125 were first developed and tested on 989 patients receiving first line therapy and have since been tested on over 2000 patients in phase 2 trials . Precise definitions for progression were developed from 71 patients during and on 255 patients both during and after initial chemotherapy . RESULTS In individual patient management , progression on initial chemotherapy can be demonstrated by serial rise in CA 125 suggesting the need for a change in therapy . A confirmed doubling of CA 125 from the upper limit of normal during follow up accurately predicts relapse . This endpoint needs prospect i ve testing for use in clinical trials . Precise definitions of response based on a 50 % or 75 % fall in CA 125 levels accurately predicts whether a cytotoxic agent is active against ovarian cancer . CONCLUSION Precise definitions of response based on CA 125 should be used in phase 2 trials of new cytotoxic drugs PURPOSE A large , r and omized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity . In this study , a number of patients crossed over to the alternative drug as third-line therapy , ie , from paclitaxel to topotecan and vice versa . We therefore were able to assess the degree of non-cross-resistance between these two compounds . PATIENTS AND METHODS Patients who had progressed after one platinum-based regimen were r and omized to either topotecan ( 1.5 mg/m(2)/d ) x 5 every 21 days ( n = 112 ) or paclitaxel ( 175 mg/m(2 ) over 3 hours ) every 21 days ( n = 114 ) . A total of 110 patients received cross-over therapy with the alternative drug ( 61 topotecan , 49 paclitaxel ) as third-line therapy . RESULTS Response rates to third-line cross-over therapy were 13.1 % ( 8 of 61 topotecan ) and 10.2 % ( 5 of 49 paclitaxel ; P = .638 ) . Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment . Median time to progression ( from the start of third-line therapy ) was 9 weeks in both groups , and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel , respectively . The principal toxicity was myelosuppression ; grade 4 neutropenia was more frequent with topotecan ( 81.4 % of patients ) than with paclitaxel ( 22.9 % of patients ) . CONCLUSION Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival . We demonstrated that the two drugs have a degree of non-cross-resistance . Thus , there is a good rationale for incorporating these drugs into future first-line regimens The last few years have seen an increase in the number of r and omized controlled trials ( RCTs ) of new agents in metastatic solid tumors using progression-free survival ( PFS ) as the primary end point . Some trials showing improvement in PFS , without a correspondingincreaseinoverallsurvival(OS),haveledtoapprovalofnew drugs and /or changes in st and ard of care . This suggests a growing belief in the oncology community that delaying progression in metastaticdiseaseisaworthy goal , evenifOSisnotimproved . Butisanew treatment that improves PFS really an advance for patients ? Or is it only lowering the bar to declare active some of our much-heralded new molecular targeted therapies ? We believe that as a community , this trend requires discussion and debate AIM Trabectedin in combination with pegylated liposomal doxorubicin ( PLD ) improves progression-free survival ( PFS ) compared to PLD alone in recurrent ovarian cancer ( J Clin Oncol 2010;28:3107 - 14 ) . METHODS Women , stratified by performance status ( 0 - 1 versus 2 ) and platinum sensitivity ( platinum-free interval [PFI]<6 versus ≥ 6 months ) , were r and omly assigned to receive PLD 30 mg/m(2 ) IV followed by a 3-h infusion of trabectedin 1.1mg/m(2 ) every 3 weeks or PLD 50mg/m(2 ) every 4 weeks . The study was powered to show a 33 % increase in overall survival ( OS ) after 520 deaths had occurred . RESULTS After a median follow-up of 47.4 months , there were 522 deaths among 672 subjects . The median OS for trabectedin+PLD and PLD arms was 22.2 and 18.9 months , respectively ( hazard ratio [HR]=0.86 ; 95 % confidence interval [ CI ] : 0.72 - 1.02 ; p=0.0835 ) . An unexpected but significant imbalance in the PFI favouring the PLD arm ( mean PFI : PLD=13.3 months , trabectedin+PLD=10.6 months ) was identified . On the basis of this finding , an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin+PLD arm ( HR=0.82 ; 95%CI : 0.69 - 0.98 ; p=0.0285 ) . In another unplanned exploratory analysis , the subset of patients with a PFI of 6 - 12 months had the largest difference in OS ( HR=0.64 ; 95%CI : 0.47 - 0.86 ; p=0.0027 ) . CONCLUSIONS The final OS analysis did not meet the protocol -defined criterion for statistical significance . Despite stratification on platinum sensitivity , there was an imbalance in mean platinum free interval that had an effect on OS A multicentre , r and omised study was carried out in Europe , South Africa and North America to compare the activity and tolerability of oral versus intravenous ( i.v . ) topotecan in patients with relapsed epithelial ovarian cancer . Patients who had failed first-line therapy after one platinum-based regimen , which could have included a taxane , were r and omised to treatment with either oral ( p.o . ) topotecan , 2.3 mg/m(2)/day or i.v . topotecan 1.5 mg/m(2)/day for 5 days every 21 days . Patients were stratified by prior paclitaxel exposure , interval from previous platinum therapy and tumour diameter . 266 patients were r and omised . Response rates were 13 % orally ( p.o . ) and 20 % ( i.v . ) with a complete response in 2 and 4 patients , respectively . The difference in the response rates was not statistically significant . Median survival was 51 weeks ( p.o . ) and 58 weeks ( i.v . ) with a risk ratio of death ( p.o . to i.v . treatment ) of 1.361 ( 95 % confidence interval ( CI ) : 1.001 , 1.850 ) . Median time to progression was 13 weeks ( p.o . ) and 17 weeks ( i.v . ) . The principal toxicity was myelosuppression although grade 3/4 neutropenia occurred less frequently in those receiving oral topotecan . Toxicity was non-cumulative and infectious complications were relatively infrequent . Non-haematological toxicity was generally mild or moderate . The incidence of grade 3/4 gastrointestinal events was slightly higher for oral than i.v . topotecan . Oral topotecan shows activity in second-line ovarian cancer and neutropenia may be less frequent than with the i.v . formulation . A small , but statistically significant , difference in survival favoured the i.v . formulation , but the clinical significance of this needs to be interpreted in the context of second-line palliative treatment . Oral topotecan is convenient and well tolerated and further studies to clarify its role are ongoing PURPOSE Topotecan and paclitaxel were evaluated in a r and omized , multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen . PATIENTS AND METHODS Patients received either topotecan ( 1.5 mg/m2 ) as a 30-minute infusion daily for 5 days every 21 days ( n = 112 ) or paclitaxel ( 175 mg/m2 ) infused over 3 hours every 21 days ( n = 114 ) . Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity . RESULTS Response rate was 23 of 112 ( 20.5 % ) in topotecan-treated patients and 15 of 114 ( 13.2 % ) in paclitaxel-treated patients ( P = .138 ) . Disease stabilization for at least 8 weeks was noted in 30 % of patients with topotecan and 33 % of patients with paclitaxel . Median duration s of response to topotecan and paclitaxel were 32 and 20 weeks , respectively ( P = .222 ) and median times to progression were 23 and 14 weeks , respectively ( P = .002 ) . Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel ( P = .515 ) . Response rates for topotecan and paclitaxel were 13.3 % versus 6.7 % ( P = .303 ) in resistant patients ( not responded to prior platinum-based therapy or progressed within 6 months of an initial response ) and 28.8 % versus 20.0 % ( P = .213 ) in sensitive patients ( progressed > 6 months after response ) . Neutropenia was significantly more frequent on the topotecan arm 79 % versus paclitaxel arm 23 % ( P < .01 ) . It was short-lasting and noncumulative in both arms . Nonhematologic toxicities were generally mild ( grade s 1 to 2 ) for both agents . CONCLUSION Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates ( GFR ) in the range of 33 to 136 mL/min . Carboplatin plasma clearance was linearly related to GFR ( r = 0.85 , P less than .00001 ) and rearrangements of the equation describing the correlation gave the dosage formula dose ( mg ) = target area under the free carboplatin plasma concentration versus time curve ( AUC ) x ( 1.2 x GFR + 20 ) . In a prospect i ve clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients ( GFR range , 33 to 135 mL/min ) with 40 courses of carboplatin . The target AUC was escalated from 3 to 8 mg carboplatin/mL/min . Over this AUC range the formula accurately predicted the observed AUC ( observed/predicted ratio 1.24 + /- 0.11 , r = 0.886 ) and using these additional data , the formula was refined . Dose ( mg ) = target AUC x ( GFR + 25 ) is now the recommended formula . AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients , respectively , and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups . Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics , assuming that body size did not influence nonrenal clearance . The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found ( r = .31 , P = .30 ) . Therefore , the formula provides a simple and consistent method of determining carboplatin dose in adults . Since the measure of carboplatin exposure in the formula is AUC , and not toxicity , it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures . The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy , although the target AUC for carboplatin will need to be redefined for combination chemotherapy |
559 | 28,905,305 | The majority of these studies review ed used pre-post , posttest only with control group , or quasi-experience design s. The Health Belief Model was the most commonly used theory in both groups .
Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies .
Small media and group education were the top two most popular intervention strategies in both groups .
Although one-on-one strategy was used in some Latino studies , neither group used reducing client out-of-pocket costs strategy .
Client reminders could also be used more in both groups as well .
Current review showed church-based cancer education programs were effective in changing knowledge , but not always screening utilization .
Results show faith-based cancer educational interventions are promising . | Church-based interventions have been used to reach racial/ethnic minorities .
In order to develop effective programs , we conducted a comprehensive systematic review of faith-based cancer prevention studies ( 2005~2016 ) to examine characteristics and promising strategies . | Introduction The Tepeyac Project is a church-based health promotion project that was conducted from 1999 through 2005 to increase breast cancer screening rates among Latinas in Colorado . Previous reports evaluated the project among Medicare and Medicaid enrollees in the state . In this report , we evaluate the program among enrollees in the state 's five major insurance plans . Methods We compared the Tepeyac Project 's two interventions : the Printed Intervention and the Promotora Intervention . In the first , we mailed culturally tailored education packages to 209 Colorado Catholic churches for their use . In the second , promotoras ( peer counselors ) in four Catholic churches delivered breast-health education messages personally . We compared biennial mammogram cl aims from the five insurance plans in the analysis at baseline ( 1998–1999 ) and during follow-up ( 2000–2001 ) for Latinas who had received the interventions . We used generalized estimating equations ( GEE ) analysis to adjust rates for confounders . Results The mammogram rate for Latinas in the Printed Intervention remained the same from baseline to follow-up ( 58 % [ 2979/5130 ] vs 58 % [ 3338/5708 ] ) . In the Promotora Intervention , the rate was 59 % ( 316/536 ) at baseline and 61 % ( 359/590 ) at follow-up . Rates increased modestly over time and varied widely by insurance type . After adjusting for age , income , urban versus rural location , disability , and insurance type , we found that women exposed to the Promotora Intervention had a significantly higher increase in biennial mammograms than did women exposed to the Printed Intervention ( GEE parameter estimate = .24 [ ±.11 ] , P = .03 ) . Conclusion For insured Latinas , personally delivering church-based education through peer counselors appears to be a better breast-health promotion method than mailing printed educational material s to churches Background Cancer is the leading cause of death among Asian Americans . While Asian Americans are the fastest growing minority population in the United States , they are underrepresented in cancer research and report poor adherence to cancer screening guidelines . Purpose This study utilized data from two large r and omized intervention trials to evaluate strategies to recruit first-generation Chinese American immigrants from community setting s and Chinese American physician practice s. Findings will inform effective strategies for promoting Asian American participation in cancer control research . Methods Chinese Americans who were non-adherent to annual mammography screening guidelines ( Study 1 with 664 immigrant women > 40 years of age ) and to colorectal cancer screening guidelines ( Study 2 with 455 immigrants > 50 years of age ) were enrolled from the greater Washington DC , New York City ( NYC ) , and Philadelphia ( PA ) areas . Both studies trained bilingual staff to enroll Chinese-speaking participants with the aid of linguistically appropriate fliers and brochures to obtain consent . Study 1 adopted community approaches and worked with community organizations to enroll participants . Study 2 r and omly selected potential participants through 24 Chinese American primary -care physician offices , and mailed letters from physicians to enroll patients , followed by telephone calls from research staff . The success of recruitment approaches was assessed by yield rates based on number of participants approached , ineligible , and consented . Results Most participants ( 70 % ) of Study 1 were enrolled through in-person community approaches ( e.g. , Chinese schools , stores , health fairs , and personal networks ) . The final yield of specific venues differed widely ( 6 % to 100 % ) due to various proportions of ineligible subjects ( 2%–64 % ) and refusals ( 0%–92 % ) . The Study 2 recruitment approach ( physician letter followed by telephone calls ) had different outcomes in two geographic areas , partially due to differences in demographic characteristics in the DC and NYC/PA areas . The community approaches enrolled more recent immigrants and uninsured Chinese Americans than the physician and telephone call approach ( p < .001 ) . Enrollment cost is provided to inform future research studies . Limitations Our recruitment outcomes might not be generalizable to all Chinese Americans or other Asian American population s because they may vary by study protocol s ( e.g. , length of trials ) , target population s ( i.e. , eligibility criteria ) , and available re sources . Conclusions Use of multiple culturally relevant strategies ( e.g. , building trusting relationships through face-to-face enrollment , use of bilingual and bicultural staff , use of a physician letter , and employing linguistically appropriate material s ) was crucial for successfully recruiting a large number of Chinese Americans in community and clinical setting s. Our data demonstrate that substantial effort is required for recruitment ; studies need to budget for this effort to ensure the inclusion of Asian Americans in health research OBJECTIVES To describe both conditions of a two-group r and omized trial , one that promotes physical activity and one that promotes cancer screening , among churchgoing Latinas . The trial involves promotoras ( community health workers ) targeting multiple levels of the Ecological Model . This trial builds on formative and pilot research findings . DESIGN Sixteen churches were r and omly assigned to either the physical activity intervention or cancer screening comparison condition ( approximately 27 women per church ) . In both conditions , promotoras from each church intervened at the individual- ( e.g. , beliefs ) , interpersonal- ( e.g. , social support ) , and environmental- ( e.g. , park features and access to health care ) levels to affect change on target behaviors . MEASUREMENTS The study 's primary outcome is min/wk of moderate-to-vigorous physical activity ( MVPA ) at baseline and 12 and 24 months following implementation of intervention activities . We enrolled 436 Latinas ( aged 18 - 65 years ) who engaged in less than 250 min/wk of MVPA at baseline as assessed by accelerometer , attended church at least four times per month , lived near their church , and did not have a health condition that could prevent them from participating in physical activity . Participants were asked to complete measures assessing physical activity and cancer screening as well as their correlates at 12- and 24-months . SUMMARY Findings from the current study will address gaps in research by showing the long term effectiveness of multi-level faith-based interventions promoting physical activity and cancer screening among Latino communities BACKGROUND Despite evidence of a decline in both incidence and prevalence of colorectal cancer nationwide , it remains the second most commonly diagnosed cancer and the third highest cause of mortality among Asian Americans , including Korean Americans . This community-based and theoretically guided study evaluated a culturally appropriate intervention program that included a bilingual cancer educational program among Korean Americans including information on CRC risks , counseling to address psychosocial and access barriers , and patient navigation assistance . METHODS A two-group quasi-experimental design with baseline and post-intervention assessment and a 12-month follow-up on screening was used in the study . Korean Americans ( N=167 ) were enrolled from six Korean churches . The intervention group received culturally appropriate intervention program addressing accessibility and psychosocial barriers , and navigation assistance for screening . The control group received general health education that included cancer-related health issues and screening . RESULTS There was a significant difference ( p<0.05 ) between the post-intervention and control groups in awareness of CRC risk factors . There was also a significant improvement in the pre-post across HBM measures in the intervention group for perceived susceptibility ( p<0.05 ) and benefits and barriers to screening ( p<0.001 ) . At baseline , 13 % of participants in the intervention group and 10 % in control group reported having had a CRC cancer screening test in the previous year . At the 12-month post-intervention follow-up , 77.4 % of participants in the intervention group had obtained screening compared to 10.8 % in the control group . CONCLUSION While health disparities result from numerous factors , a culturally appropriate and church-based intervention can be highly effective in increasing knowledge of and access to , and in reducing barriers to CRC screening among underserved Koreans INTRODUCTION Health communication interventions have been modestly effective for increasing informed decision making for prostate cancer screening among African-American men ; however , knowledge and informed decision making is still question able even with screening . Church-based programs may be more effective if they are spiritually based in nature . OBJECTIVE The aims of the present study were to implement and provide an initial evaluation of a spiritually based prostate cancer screening informed decision making intervention for African-American men who attend church , and determine its efficacy for increasing informed decision making . DESIGN AND METHOD Churches were r and omized to receive either the spiritually based or the non-spiritual intervention . Trained community health advisors , who were African-American male church members , led an educational session and distributed educational print material s. Participants completed baseline and immediate follow-up surveys to assess the intervention impact on study outcomes . RESULTS The spiritually based intervention appeared to be more effective in areas such as knowledge , and men read more of their material s in the spiritually based group than in the non-spiritual group . CONCLUSIONS Further examination of the efficacy of the spiritually based approach to health communication is warranted Background . African American ( AA ) men continue to have a greater than twofold risk of dying from prostate cancer compared to Whites . Methods . This community-based intervention study employed a quasi-experimental , delayed-control ( cross-over ) design with r and omization at the church-level ( N=345 AA men ) . Results . Logistic regression analyses revealed that the level of knowledge ( b=.61 , P<.05 , Exp (B)=1.84 ) , the perception of risk ( b=2.99 , P<.01 , Exp (B)=19.95 ) , and having insurance ( b=3.20 , P<.01 , Exp (B)=24.65 ) significantly increased the odds of participants who needed screening getting screened during study . Discussion . This study demonstrated the need for education , community involvement , and increased access to encourage minority men to obtain needed health screenings |
560 | 29,132,613 | No evidence of publication bias was found in this analysis of studies of diagnostic value .
INTERPRETATION Current WHO guidelines appear to manage dysentery effectively , but might miss opportunities to reduce mortality among children infected with Shigella who present without bloody stool . | BACKGROUND Shigella infections are a leading cause of diarrhoeal death among children in low-income and middle-income countries .
WHO guidelines reserve antibiotics for treating children with dysentery .
Reliance on dysentery for identification and management of Shigella infection might miss an opportunity to reduce Shigella-associated morbidity and mortality .
We aim ed to systematic ally review and evaluate Shigella-associated and dysentery-associated mortality , the diagnostic value of dysentery for the identification of Shigella infection , and the efficacy of antibiotics for children with Shigella or dysentery , or both . | Shigellosis is still an important health problem in developing and underdeveloped countries as it is resistance to commonly used antibiotics including ampicillin , trimethoprim-sulfamethoxazole , chloramphenicol and tetracycline . Between May 1996 and October 1996 , in a prospect i ve r and omized double-blind trial , cefixime was compared with ampicillin-sulbactam , both given orally for a period of 5 days , for the treatment of 80 children with acute bloody diarrhea . Forty patients were treated with a single-dose ( 8 mg/kg per day ) of cefixime and the other 40 patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam . After identification of Shigella organisms in stool specimens , nine patients in the cefixime receiving group and six patients in the ampicillin-sulbactam receiving group were excluded from the study . Differences in average age , sex and weight between the cefixime and ampicillin-sulbactam group were statistically meaningless ( P > 0.05 ) . Fever and bloody diarrhea were universal features . The efficacy of cefixime was found to be better than ampicillin-sulbactam . Patients given cefixime had a shorter duration of fever ( P < 0.01 ) , shorter duration to disappearance of blood in the stool ( P < 0.01 ) , reduced time with diarrhea ( P < 0.01 ) and reduced hospitalization time during the 5 study days ( P < 0.01 ) than patients given ampicillin-sulbactam . No adverse effects were observed in the two study groups . This controlled trial showed good efficacy with cefixime compared to ampicillin-sulbactam in the treatment of shigellosis . Single-dose daily oral therapy with cefixime also showed good tolerability . Cefixime should be considered as an alternative drug of choice for shigellosis in children A single-blind , parallel , r and omized study comparing the efficacy of furazolidone and ampicillin in the treatment of children with acute invasive diarrhea was conducted among out patients at the Hospital General de Ciudad Nezahualcoyotl in Mexico between August 1986 and October 1987 . Seventy-eight patients were admitted to the study ; 39 were r and omized to receive furazolidone ( 5 mg/kg/day for 5 days ) , and 39 were r and omized to receive ampicillin ( 100 mg/kg/day for 5 days ) . The enteropathogens Shigella sp , Salmonella sp , and Escherichia coli were isolated in 87.2 % of the initial stool cultures . A preliminary assessment of the patients ' clinical status was made on day 3 . At that time 97.4 % of furazolidone patients had improved , compared with 65.7 % of patients in the ampicillin group ( p = 0.002 ) . At the end of the treatment period ( day 6 ) , 100 % of evaluable patients treated with furazolidone had a negative stool culture , compared with 71 % of evaluable patients treated with ampicillin ( p = 0.002 ) . Both absence of watery stools by day 5 and a negative day 6 stool culture determined treatment success . Overall , there was a greater percentage of treatment successes in the furazolidone group than in the ampicillin group ( 92.3 % versus 51.3 % , p = 0.001 ) . Tolerance to both drugs was very good . One patient treated with ampicillin developed urticaria , which required discontinuation of treatment ; the reaction resolved spontaneously after treatment discontinuation . No adverse reactions were reported in the furazolidone group . The results of this study showed that furazolidone was more effective than ampicillin in the treatment of acute invasive diarrhea . It is suggested that furazolidone should be the treatment of choice for this disease Background The burden of shigellosis is greatest in re source -poor countries . Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year , little recent data are available to guide intervention strategies in Asia . We conducted a prospect i ve , population -based study in six Asian countries to gain a better underst and ing of the current disease burden , clinical manifestations , and microbiology of shigellosis in Asia . Methods and Findings Over 600,000 persons of all ages residing in Bangladesh , China , Pakistan , Indonesia , Vietnam , and Thail and were included in the surveillance . Shigella was isolated from 2,927 ( 5 % ) of 56,958 diarrhoea episodes detected between 2000 and 2004 . The overall incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in all ages and 13.2/1,000/y in children under 60 months old . Shigellosis incidence increased after age 40 years . S. flexneri was the most frequently isolated Shigella species ( 1,976/2,927 [ 68 % ] ) in all sites except in Thail and , where S. sonnei was most frequently detected ( 124/146 [ 85 % ] ) . S. flexneri serotypes were highly heterogeneous in their distribution from site to site , and even from year to year . PCR detected ipaH , the gene encoding invasion plasmid antigen H in 33 % of a sample of culture-negative stool specimens . The majority of S. flexneri isolates in each site were resistant to amoxicillin and cotrimoxazole . Ciprofloxacin-resistant S. flexneri isolates were identified in China ( 18/305 [ 6 % ] ) , Pakistan ( 8/242 [ 3 % ] ) , and Vietnam ( 5/282 [ 2 % ] ) . Conclusions Shigella appears to be more ubiquitous in Asian impoverished population s than previously thought , and antibiotic-resistant strains of different species and serotypes have emerged . Focusing on prevention of shigellosis could exert an immediate benefit first by substantially reducing the overall diarrhoea burden in the region and second by preventing the spread of panresistant Shigella strains . The heterogeneous distribution of Shigella species and serotypes suggest that multivalent or cross-protective Shigella vaccines will be needed to prevent shigellosis in Asia Following a nationwide outbreak of Shigella dysentery type 1 and the recognition of Shigella isolates resistant to ampicillin , the drug of choice , we conducted a clinical trial to compare the efficacy of ampicillin v. trimethoprim-sulphamethoxazole for the treatment of Shigella dysentery . Patients with symptoms of dysentery and no other complicating illness were r and omized into one of two treatment groups . Patients in the two groups were comparable at the time of hospital admission with regard to age , sex , presenting complaints and Shigella strains . They responded well with both regimens and there was no significant difference in the mean time until stool became culture negative ( 1.4 days ) , temperatures returned to normal ( 2.7 days ) and faecal leucocytes disappeared ( 3.0 days ) ; abdominal pain , tenesmus and stool blood and mucus improved significantly more rapidly with trimethoprim-sulphamethoxazole than with ampicillin . There was no evidence of toxicity with either drug . While both drugs are effective for the treatment of Shigella dysentery , trimethoprim-sulphamethoxazole was considered to be superior BACKGROUND Shigella species infections coupled with increased levels of antimicrobial resistances are major public health problems in developing countries particularly in children . OBJECTIVES The present study was conducted to determine the prevalence and antimicrobial resistance pattern of Shigella species among patients with diarrhea at Felege Hiwot Referral Hospital . METHODS A cross-sectional prospect i ve study was undertaken among patients with diarrhea ( n=215 ) from August to November 2009 . A4 pre-tested structured question naire was used for collecting data . Stool sample s were investigated for identification of Shigella species following st and ard procedures and antimicrobial susceptibility tests were performed using disc diffusion technique . RESULTS The isolation rate of Shigella species was 32/215 [ 14.9 % ( 95 % CI . : 10.5 - 20.5 ) ] , with high prevalence in patents under five years of age . Educational level , latrine usage , source of drinking water , and h and washing habits showed a statistically significant association with the prevalence of Shigella species ( p = 0.004 ) . All isolates of Shigella species were susceptible to ciprofloxacin and high level of sensitivity was observed for norfloxacin ( 90.6 % ) and gentamicin ( 75 % ) . Multiple drug resistance to as many as nine antibiotics was also detected CONCLUSION High prevalence of Shigella with multiple antibiotic resistance isolates was observed in this study . Public health workers should emphasize , on primary preventive measures and periodic surveillance for antibiotic susceptibility pattern of Shigella isolates . When culturing and antibiotic susceptibility testing facilities are not available , prescription of ciprofloxacin as a choice of treatment is recommended A prospect i ve r and omized study was conducted at an infectious disease hospital in Thail and . Ceftibuten was compared with norfloxacin , both given orally for five days for treatment of acute gastroenteritis in children . One hundred and seventy cases were included in the study . Eighty-eight cases were treated with ceftibuten and eighty-two cases with norfloxacin . The baseline characteristics of the patients in both treatment groups were similar . The results showed that mean duration s of diarrhea in the ceftibuten and norfloxacin groups were 2.48 days and 2.29 days , respectively , but there was no statistically significant difference between the two groups ( p > 0.05 ) . There were Salmonella spp and Shigella spp isolated in both treatment groups and all were susceptible to both antibiotics . The mean duration s of Salmonella diarrhea in the ceftibuten and norfloxacin groups were 2.7 and 2.2 days , respectively , while those of Shigella diarrhea were 2.3 days and 2.0 days , respectively . There were no statistically significant differences in either comparison ( p > 0.05 ) . Neither complications nor clinical relapses were observed after both antibiotics ' treatment Background The bacterial genus Shigella is the leading cause of dysentery . There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid . While nalidixic acid is no longer considered as a therapeutic agent for shigellosis , the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization . Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones , such as ciprofloxacin . We aim ed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children . Methodology /Principal Findings We conducted a r and omized , open-label , controlled trial with two parallel arms at two hospitals in southern Vietnam . The study was design ed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate . Participants received either gatifloxacin ( 10 mg/kg/day ) in a single daily dose for 3 days or ciprofloxacin ( 30 mg/kg/day ) in two divided doses for 3 days . The primary outcome measure was treatment failure ; secondary outcome measures were time to the cessation of individual symptoms . Four hundred and ninety four patients were r and omized to receive either gatifloxacin ( n = 249 ) or ciprofloxacin ( n = 245 ) , of which 107 had a positive Shigella stool culture . We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups ( gatifloxacin ; 12.0 % and ciprofloxacin ; 11.0 % , p = 0.72 ) . The median ( inter-quartile range ) time from illness onset to cessation of all symptoms was 95 ( 66–126 ) hours for gatifloxacin recipients and 93 ( 68–120 ) hours for the ciprofloxacin recipients ( Hazard Ratio [ 95%CI ] = 0.98 [ 0.82–1.17 ] , p = 0.83 ) . Conclusions We conclude that in Vietnam , where nalidixic acid resistant Shigellae are highly prevalent , ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis . Trial Registration Controlled trials number IS RCT The efficacy of oral pivmecillinam was compared with nalidixic acid in the treatment of acute shigellosis in children 1 - 8 years of age . In a double-blind trial we studied 80 comparable children with bloody diarrhoea of less than 3 days ' duration . Shigella spp . was isolated in 71 children . Patients were r and omly assigned to receive either pivmecillinam , 50 mg/kg.day , or nalidixic acid , 60 mg/kg.day , both given orally for 5 days . The stool frequency decreased progressively in both treatment groups . Nalidixic acid failed to eradicate Shigella species in 10 patients , compared with three in the pivmecillinam group ( p = 0.04 ) . Similarly , clinical failure was observed in 11 of 37 patients receiving nalidixic acid and in 2 of 26 patients infected with nalidixic acid-susceptible strains as against none in the group receiving pivmecillinam . The results suggest that pivmecillinam given orally was , in fact , more effective than nalidixic acid in the treatment of acute shigellosis in children , particularly when the resistant strains are taken into account Nalidixic acid ( NA : 55 mg/kg daily for 5 days ) is the recommended treatment for uncomplicated bacillary dysentery in areas where multidrug-resistant Shigella are prevalent . An open r and omized comparison of this NA regimen with 2 doses of ofloxacin ( total 15 mg/kg ) was conducted in 1995/96 in 135 Vietnamese children with fever and bloody diarrhoea . Sixty-six children with a bacterial pathogen isolated were eligible for analysis . Of the 63 Shigella isolates , 39 ( 62 % ) were resistant to multiple antibiotics . Resolution times for fever and diarrhoea were similar in the 2 groups , but excretion time of stool pathogen was significantly longer in the NA recipients [ median ( range ) days 1 ( 1 - 9 ) vs 1 ( 1 - 2 ) , P = 0.001 ] . There were 9 ( 25 % ) treatment failures in the NA regimen and 3 ( 10 % ) in the ofloxacin group ; P = 0.1 . Two patients had NA-resistant Shigella flexneri . One of these isolates was selected during NA treatment . From a clinical and public health st and point a 2-dose regimen of ofloxacin is preferable to nalidixic acid in the treatment of bacillary dysentery In a r and omized , double‐blind clinical trial , the efficacy and safety of norfloxacin were compared with nalidixic acid in the treatment of shigellosis in children . Out of 59 cases , Shigella spp . were isolated from 8 cases in the nalidixic acid group and 14 cases in the norfloxacin group . The norfloxacin group had significantly less duration of diarrhoea and presence of blood in stool as compared to the nalidixic acid group . No joint problem was encountered in this study at up to 4 months follow‐up . Norfloxacin is safe and effective and showed no cartilage toxicity on short‐term follow‐up BACKGROUND Infections caused by multiply resistant Shigella species are a major cause of childhood morbidity and mortality in Third World countries . The fluoroquinolone agent ciprofloxacin is active in vitro against these strains of bacteria , but has not been routinely used to treat acute childhood infections because of concern that quinolones may cause arthropathy in children . We undertook a r and omised double-blind study to test the effects of ciprofloxacin treatment in children with shigella dysentery . METHODS We compared the efficacy and toxic effects of ciprofloxacin suspension ( 10 mg/kg every 12 h for 5 days , maximum individual dose 500 mg ) with those of pivmecillinam tablets ( 15 - 20 mg/kg every 8 h for 5 days , maximum individual dose 300 mg ) . We enrolled 143 children aged 2 - 15 years with dysentery of 72 h or less duration . Patients stayed in hospital for 6 days , and were followed up 7 , 30 , and 180 days after hospital discharge . Joint symptoms and function were assessed daily for 6 days . Clinical success was defined as the absence of frank dysentery on day 3 , and on day 5 no bloody-mucoid stools , one or no watery stool , six or fewer total stools , and no fever . If no shigella were isolated from faecal sample s on day 3 or thereafter , treatment was judged bacteriologically successful . FINDINGS 13 patients were excluded since they did not meet eligibility criteria ; 10 withdrew before day 5 . Thus 120 patients ( 60 in each group ) completed the study . Treatment was clinical ly successful in 48 ( 80 % ) of 60 patients who received ciprofloxacin and in 39 ( 65 % ) of 60 patients who received pivmecillinam ( p=0.10 ) . Treatment was bacteriologically successful in all of the patients receiving ciprofloxacin , and in 54 ( 90 % ) of the patients receiving pivmecillinam ( p=0.03 ) . Joint pain after treatment began in 13 ( 18 % ) of 71 patients who received ciprofloxacin and 16 ( 22 % ) of 72 patients who received pivmecillinam ( p>0.2 ) , and no patient had signs of arthritis . INTERPRETATION In our trial , ciprofloxacin suspension and pivmecillinam had the same clinical efficacy . Ciprofloxacin had greater bacteriological efficacy and was not associated with the development of arthropathy . We conclude that ciprofloxacin is an effective and safe drug for use in multiply resistant childhood shigellosis An outpatient study of 125 children with acute invasive diarrhea was conducted at the Hospital Infantil de Mexico Federico Gomez . Through a single-blind r and omization , we compared the efficacy of furazolidone , 7.5 mg/kg/day ( 49 patients ) , with trimethoprim-sulfamethoxazole ( TMP-SMX ) , 8 mg/40 mg/kg/day ( 52 patients ) , each given for 5 days . A control group of 24 patients received no antimicrobials . Stool sample s were collected from all patients at the time of admission , and active drugs were administered before the stool culture results were available . At baseline , 48 of 125 patients ( 38.5 % ) had negative stool cultures . In the other patients , the most frequently isolated pathogens were Shigella sp and enteropathogenic Escherichia coli . Of the total population who completed the study 43 of 49 ( 87.8 % ) of the patients in the furazolidone group and 43 of 52 ( 82.7 % ) of the patients in the TMP-SMX group achieved clinical cure by day 3 , compared with 10 of 22 ( 45.5 % ) of the patients in the control group . Day 3 cure rates were similar between groups , independent of baseline stool culture results . Of those patients who had positive stool cultures on day 1 , 20 of 34 ( 58.8 % ) in the furazolidone group and 19 of 29 ( 65.5 % ) in the TMP-SMX group had negative culture results on day 6 , compared with 4 of 12 ( 33.3 % ) in the control group . Overall , clinical and bacteriologic success was achieved in 31 of 49 ( 63 % ) patients treated with furazolidone and in 36 of 52 ( 69 % ) patients treated with TMP-SMX , compared with 5 of 22 ( 23 % ) patients in the control group . ( ABSTRACT TRUNCATED AT 250 WORDS A prospect i ve epidemiological and clinical study of acute diarrhea in children under 5 years old was done at King Mongkut Prachomklao Hospital in order to provide baseline data for health officers to make a strategic plan to reduce the diarrheal mortality and morbidity , which is one of the mid-decade goals for children . There were 105 cases of acute diarrhea patients admitted to the Pediatric ward between May 1995 and April 1996 . Seventy-six per cent of them were in the younger age group ( > 1 month-2 years old ) while 23.8 per cent were in the older age group ( 2 - 5 years old ) . Causative pathogens were identified in 64 patients ( 61 % ) . Younger patients had a higher percentage of identifiable pathogens ( 66.7 % ) than older patients ( 44.4 % ) . Rotavirus was the most common pathogen isolated ( 17.2 % ) . The other common pathogens identified were Eschericia coli ( 14.1 % ) , Campylobacter jejuni ( 14.1 % ) , Shigella ( 12.5 % ) , Entamoeba histolytica ( 7.8 % ) and Salmonella ( 3.1 % ) . Mixed infections were reported in 31.3 per cent of these patients . Clinical presentations and stool characteristics were difficult to distinguish from most of the pathogens . However , Rotavirus was highly suspected if a younger child presented with fever , watery to loose stool with the predominant symptom of vomiting . Mucous , mucous-bloody stool gave a clue to the diagnosis of Shigella and Entamoeba histolytica . Most cases had at least mild to moderate dehydration , so oral rehydration solution ( ORS ) was successfully given in only 31.4 per cent of patients . Antibiotics were prescribed to 51.4 per cent of patients in this study . Healthcare personnel should emphasize to parents and caretakers about good hygienic behavior to reduce the episodes of diarrhea and the use of ORS every time when their children have diarrheal episodes to reduce the disease severity BACKGROUND Diarrheal disease is a leading cause of death for young children . Most pediatric gastroenteritis is caused by viral pathogens ; consequently , current recommendations advocate against routine antibacterial therapy if children present without bloody stools . METHODS In this prospect i ve cohort study , we enrolled children with severe acute gastroenteritis admitted to hospital in Botswana . Details of presenting history , physical examination , and course in the hospital were recorded . Stool sample s were characterized using a 15 pathogen polymerase chain reaction assay . RESULTS There were 671 participants with a median age of 8.3 months ; 77 ( 11 % ) had severe acute malnutrition . Only 74 children had bloody stools , of whom 48 ( 65 % ) had a detectable bacterial pathogen , compared to 195 of 592 ( 33 % ) of those without . There were 26 deaths ( 3.9 % ) . Covariates associated with death in multivariable logistic regression were the detection of any of Campylobacter/Shigella/enterotoxigenic Escherichia coli ( odds ratio [ OR ] 2.57 , 95 % confidence interval [ CI ] 1.07 - 6.17 ) , severe acute malnutrition ( OR 4.34 , 95 % CI 1.79 - 10.5 ) , and antibiotic therapy ( OR 8.82 , 95 % CI 2.03 - 38.2 ) . There was no significant association between bloody stools and death , and the effect of Campylobacter/Shigella/enterotoxigenic E. coli infection on death was not modified by the presence of bloody stools . CONCLUSIONS Detection of bacterial enteropathogens is associated with increased mortality in children in sub-Saharan Africa . Unfortunately , most children with these infections do not have bloody stools , and bloody dysentery was not found to be associated with worse outcomes . Clinical trials evaluating outcomes associated with more aggressive diagnostic strategies in children presenting with severe acute gastroenteritis in sub-Saharan Africa should be undertaken To evaluate a more economical regimen for severe shigella dysentery , treatment with single-dose ( SD ) ampicillin ( 100 mg/kg ) was compared in a r and omized trial with results obtained in a conventional five-day ( 100 mg/kg per 24 hr ) multiple-dose ( MD ) course . Clinical relapse occurred in one of 23 SD children , no SD or MD adults , and none of 18 MD children . Bacteriologic failures were observed in six of 26 adults compared with one of 24 MD adults ( P = 0.05 ) . Four of 10 SD children younger than four years of age failed bacteriologically , compared with one MD child . In SD children , lower ampicillin levels were significantly associated with bacteriologic failure and younger age . Resistance of Escherichia coli to ampicillin , although transiently less in SD patients , was equal in MD and SD patients two weeks after therapy . Thus , in highly endemic areas SD ampicillin is clinical ly effective therapy for ampicillin-sensitive shigellosis in patients older than four years of age To compare the efficacy of oral gentamicin with nalidixic acid in the treatment of acute shigellosis , we studied , in a double blind-trial , 79 comparable children with bloody diarrhoea of less than 72 h duration . Of them Shigella spp . were isolated in 71 patients . Patients were r and omly assigned to receive either gentamicin 30 mg/kg/day or nalidixic acid 60 mg/kg/day , both given orally in four equal doses for 5 days . Stool frequency differed significantly between the groups from day two until completion of the study . Treatment failure was observed in 14 ( 42 per cent ) patients receiving oral gentamicin compared to none of those with nalidixic acid-sensitive strains of Shigella spp . ( P = 0.0002 ) . Although all the shigella isolates were sensitive to gentamicin in vitro , 19 ( 58 per cent ) patients on gentamicin therapy failed to eliminate shigella organisms from stool , compared to none in the nalidixic acid treated group infected with nalidixic acid-sensitive Shigella spp . ( P < 0.001 ) . One patient in each group had a bacteriological relapse . We conclude that gentamicin given orally was therapeutically ineffective in the treatment of acute shigellosis In a prospect i ve r and omized study at two clinical sites , ceftibuten was compared with trimethoprim-sulfamethoxazole ( TMP-SMX ) , both given orally for a period of 5 days , for the treatment of dysentery . Twenty-two children were found to have bacillary dysentery caused by Shigella and /or enteroinvasive Escherichia coli . All organisms isolated were susceptible to ceftibuten ; 6 of 20 Shigella strains and 4 of 5 enteroinvasive E. coli were resistant to TMP-SMX . The diarrhea persisted for a mean ( + /- SD ) period of 2.4 + /- 1.4 days in the ceftibuten-treated patients vs. 3.4 + /- 1.7 days in the TMP-SMX-treated patients . The duration of fever was similar for both treatment groups . Patients treated with ceftibuten or TMP-SMX had equivalent clinical responses unless the pathogen was found to be TMP-SMX-resistant . Those who were r and omized to receive TMP-SMX but who were eventually found to have TMP-SMX-resistant organisms had significantly more stools at days 3 , 4 and 5 ( P less than 0.02 to less than 0.00006 ) with more watery consistency for these days ( P less than 0.02 to less than 0.005 ) compared to patients treated with ceftibuten . No clinical relapses were reported and no drug-related side effects were observed . We conclude that ceftibuten is at least as effective as TMP-SMX in the treatment of diarrhea caused by Shigella and enteroinvasive E. coli in children Erythromycin therapy was compared with no treatment in a prospect i ve trial of acute diarrheal disease among 100 infants in an orphanage in Bangkok . Within 24 h of the onset of diarrhea , 50 children received erythromycin ethylsuccinate ( 40 mg/kg per day ) in four divided doses for 5 days . Campylobacter jejuni isolated from 31 , Campylobacter coli isolated from 21 , and Shigella spp . isolated from 21 of 100 children were the most commonly recognized pathogens ; use of a sensitive , nonselective method substantially increased Campylobacter isolation . Treatment with erythromycin had no effect on the duration of diarrhea caused by Campylobacter spp . , Shigella spp . , or other agents ; 37 % of the treatment group and 35 % of the control group had diarrhea for 1 week . Of 23 Campylobacter strains isolated from the treatment group before treatment , 15 ( 65 % ) were resistant ( MIC , greater than or equal to 8 micrograms/ml ) to erythromycin . Among orphanage-acquired strains , 53 % of 43 C. jejuni strains and 91 % of 23 C. coli strains were resistant to erythromycin compared with 11 % of 114 C. jejuni strains and 46 % of 35 C. coli strains that were community acquired . Erythromycin resistance is common among Campylobacter strains in Bangkok , especially in an institutional setting , which may account for the lack of efficacy of erythromycin for treatment of acute diarrheal illnesses Background . Shigella dysenteriae type 1 ( Sd1 ) dysentery is associated with serious morbidity and mortality . Treatment is either costly or complicated by the emergence of bacterial resistance . This study compared the efficacy and safety of short course ( 3 days ) and st and ard course ( 5 days ) oral ciprofloxacin in children with Sd1 dysentery . Methods . A multicenter , r and omized , double blind , controlled clinical trial . Children between 1 and 12 years of age with Sd1 dysentery were r and omized to receive oral ciprofloxacin suspension 15 mg/kg every 12 h for 3 days followed by placebo for 2 days or ciprofloxacin suspension for 5 days . Treatment success was defined as either resolution of illness or marked improvement on Day 6 of study . Bacteriologic cure was defined as failure to grow Sd1 on a stool sample collected on Day 6 . Clinical assessment s and joint examinations were performed at baseline , at discharge and 2 weeks later . Results . Of 253 patients enrolled 128 were assigned to short course ciprofloxacin and 125 to st and ard course ciprofloxacin . The success rates were 65 and 69 % for short and st and ard course ciprofloxacin , respectively . All patients had bacteriologic cure , and all Sd1 isolates were susceptible in vitro to ciprofloxacin . No bacteriologic relapses occurred during the study period . Eight patients reported arthralgia . All patients had normal joint function including at follow-up . Conclusion . In this study twice daily ciprofloxacin for 3 days achieved clinical cure rates similar to those for the same dosage given for 5 days in children with Sd1 dysentery Efficacy of furazolidone and nalidixic acid was compared in a r and omized trial involving 72 children with acute invasive diarrhea . Thirty six children received furazolidone ( 7.5 mg/kg/day ) and 36 children received nalidixic acid ( 55 mg/kg/day ) . Clinical characteristics of the two treatment groups were comparable on admission . Of these , 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy . Clinical cure was observed in 29(85.3 % ) children treated with furazolidone and 29(100.0 % ) children treated with nalidixic acid . Nalidixic acid treated group had statistically significantly higher cure rate ( p = 0.039 ) as compared to furazolidone treated group . However , 85 % cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries We compared nalidixic acid , 55 mg/kg/day , with ampicillin , 100 mg/kg/day , both given orally for 5 days , in the treatment of children with dysentery caused by shigellosis . All patients entered into the study had illness of less than 72 hours ' duration and no prior allopathic drug therapy . Treatment was r and omized and administered in double-blind fashion . Patients initially treated with ampicillin who were infected with a Shigella strain resistant to ampicillin were considered as a separate group ( ampicillin-R ) . All isolates were susceptible to nalidixic acid . Similar percentages of patients treated with nalidixic acid ( 26/32 , 81 % ) and with ampicillin ( 17/22 , 77 % ) were clinical ly cured by the end of therapy ; the rate in ampicillin-R ( 3/14 , 21 % ) patients was significantly lower ( p less than 0.001 ) . Stool frequency in patients treated with nalidixic acid was significantly less than for ampicillin-treated or ampicillin-R patients during the final 3 study days . All patients treated with nalidixic acid and ampicillin had Shigella eradicated from their stool by day 3 , compared with 77 % ( 10/13 ) of ampicillin-R patients ( p less than 0.05 , ampicillin-R vs nalidixic acid or ampicillin ) . We conclude that nalidixic acid is an effective alternative to ampicillin in the treatment of shigellosis caused by nalidixic acid-susceptible strains To establish optimal therapy for severe dysentery due to Shigella dysenteriae type 1 and Shigella flexneri , we compared in a prospect i ve r and omized trial two oral ampicillin doses ( 50 and 150 mg/kg per day ) in 57 children and 39 adults in Dacca , Bangladesh . Clinical failure did not occur in either group , indicating that conventional doses need not be increased even in severe disease . Among children 3 years of age or under , bacteriological relapses tended to be more frequent in the low-dose group and were not related to serum levels of ampicillin , nutritional status , or the severity of colitis on admission . Therefore , we recommend that younger children be treated with 100 mg/kg per day of oral ampicillin In a prospect i ve r and omized double-blind trial , pivmecillinam was compared with cotrimoxazole ( TMP-SMX ) , both given orally for a period of 5 days , for the treatment of 59 children with shigellosis . 29 patients were treated with pivmecillinam and 30 with cotrimoxazole . 14 % of shigella organisms isolated were resistant to pivmecillinam and 21 % to TMP-SMX . The diarrhea persisted for a mean ( + /- SD ) period of 74 + /- 24.8 h in the pivmecillinam-treated patients versus 73.8 + /- 34 h in the TMP-SMX-treated patients . Duration of fever , positive stool culture , visible blood , occult blood , and pus cells in the stools were similar for both treatment groups . Five patients ( 17 % ) in the pivmecillinam group and 4 patients ( 13 % ) in the cotrimoxazole group fulfilled the clinical criteria that defined treatment failure . One patient ( 3.4 % ) in the pivmecillinam group and 2 ( 6.6 % ) in the TMP-SMX group evidence d recurrence of the diarrheal symptoms at the follow-up visit . No major drug-related side effects were observed in either group . We concluded that pivmecillinam is equivalent to cotrimoxazole in the treatment of shigellosis in children Background : Shigella is responsible for high morbidity and mortality among children , yet its true prevalence remains inconclusive . The aim of this study was to determine the actual prevalence of Shigella infection in childhood diarrhea and dysentery cases and assess the applicability of ipaH gene PCR in Indian setting s. Methods : This study was conducted at Maulana Azad Medical College and associated Lok Nayak Hospital , New Delhi , India during 2011 - 12 . A total of 385 children ( 207 with diarrhea , 118 with dysentery , and 60 matched controls ) were enrolled . Stool sample s were cultured , and the suspected colonies were analyzed using biochemical reactions and serotyping . Antimicrobial susceptibility testing was done using disc diffusion method . ipaH-gene PCR was performed directly on stool sample s collected from 180 r and omly selected patients ( 60 from each group ) . Results : Shigella was isolated using conventional culture methods in 8.2 % ( 95 % CI : 5.1 % , 12.8 % ) , 33.1 % ( 95 % CI : 25.2 % , 42.0 % ) , and 0 % in the diarrhea , dysentery and control cases , respectively . High resistance was seen towards co-trimoxazole , nalidixic acid , fluoroquinolones , doxycycline and several beta-lactams drugs . Actual prevalence of shigellosis was determined using ipaH gene PCR to be 18.3 % ( 95 % CI : 10.4 % – 30.1 % ) diarrhea cases and 56.7 % ( 95 % CI : 44.1 , 68.4 % ) dysentery cases . One ( 1.7 % , 95 % CI : 0.01 % , 9.7 % ) control specimen also yielded positive result in PCR . Conclusions : Correct diagnosis of shigellosis is essential to start antimicrobial therapy in selected cases . The prevalence of Shigella / EIEC infection in children is much higher than previously estimated . Despite its high costs and other limitations , we recommend the use of ipaH-gene PCR as a routine tool in the management of childhood acute gastroenteritis cases To evaluate the efficacy of azithromycin for treatment of shigellosis , 75 children with dysenteric diarrhea in whom Shigella was isolated were r and omized to receive either azithromycin or cefixime orally for 5 days . Treatment with azithromycin led to a significantly higher bacteriologic eradication rate ( P < 0.01 ) and a trend toward better clinical efficacy ( P = 0.1 ) than with cefixime therapy BACKGROUND Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries . We design ed the Global Enteric Multicenter Study ( GEMS ) to identify the aetiology and population -based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia . METHODS The GEMS is a 3-year , prospect i ve , age-stratified , matched case-control study of moderate-to-severe diarrhoea in children aged 0 - 59 months residing in censused population s at four sites in Africa and three in Asia . We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three r and omly selected matched community control children without diarrhoea . From patients with moderate-to-severe diarrhoea and controls , we obtained clinical and epidemiological data , anthropometric measurements , and a faecal sample to identify enteropathogens at enrolment ; one follow-up home visit was made about 60 days later to ascertain vital status , clinical outcome , and interval growth . FINDINGS We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea . By analysing adjusted population attributable fractions , most attributable cases of moderate-to-severe diarrhoea were due to four pathogens : rotavirus , Cryptosporidium , enterotoxigenic Escherichia coli producing heat-stable toxin ( ST-ETEC ; with or without co-expression of heat-labile enterotoxin ) , and Shigella . Other pathogens were important in selected sites ( eg , Aeromonas , Vibrio cholerae O1 , Campylobacter jejuni ) . Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls ( odd ratio 8·5 , 95 % CI 5·8 - 12·5 , p<0·0001 ) ; most deaths ( 167 [ 87·9 % ] ) occurred during the first 2 years of life . Pathogens associated with increased risk of case death were ST-ETEC ( hazard ratio [ HR ] 1·9 ; 0·99 - 3·5 ) and typical enteropathogenic E coli ( HR 2·6 ; 1·6 - 4·1 ) in infants aged 0 - 11 months , and Cryptosporidium ( HR 2·3 ; 1·3 - 4·3 ) in toddlers aged 12 - 23 months . INTERPRETATION Interventions targeting five pathogens ( rotavirus , Shigella , ST-ETEC , Cryptosporidium , typical enteropathogenic E coli ) can substantially reduce the burden of moderate-to-severe diarrhoea . New methods and accelerated implementation of existing interventions ( rotavirus vaccine and zinc ) are needed to prevent disease and improve outcomes . FUNDING The Bill & Melinda Gates Foundation |
561 | 18,577,254 | Conclusion This review suggests a survival benefit of heparin in cancer patients in general , and in patients with limited small cell lung cancer in particular | Background To determine the efficacy and safety of heparin ( unfractionated heparin ( UFH ) or low-molecular-weight-heparin ( LMWH ) ) and fondaparinux in improving the survival of patients with cancer . | Clinical and experimental studies have suggested that unfractionated heparin ( UFH ) effects malignancy progression . We review ed all published clinical reports concerning the effects of UFH , as compared to no treatment on survival of cancer patients . Studies were classified on method ological strength and subdivided as to whether therapeutic or prophylactic dosages of UFH were used . Mortality rates after 3 years were extracted or calculated . One r and omized study that evaluated the use of UFH in therapeutic dosages in patients with small cell lung carcinoma reported on an improved survival ( odds ratio ( OR ) 0.64 ; 95 % confidence interval ( CI ) : 0.25 to 1.62 ) . A detrimental effect was observed in 2 r and omized studies which investigated the effects of intraportal UFH treatment in a prophylactic dose after surgery for gastrointestinal cancer ( OR 1.66 ; 95 % CI : 1.02 to 2.71 ) . In contrast , level 2 studies in which either therapeutic or prophylactic dosages of UFH on mortality of patients with gastrointestinal cancer were evaluated , showed OR of 0.58 ( 95 % CI ; 0.11 - 3.13 ) and 0.65 ( 95 % CI 0.51 to 0.84 ) , respectively . We conclude that there is no convincing evidence of either positively or negatively effects of UFH on survival of patients with malignancy A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment . These complications may occur more frequently if these patients have concomitant cancer . This prospect i ve follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer . Of the 842 included patients , 181 had known cancer at entry . The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7 % ( 95 % CI , 15.6%-25.8 % ) versus 6.8 % ( 95 % CI , 3.9%- 9.7 % ) in patients without cancer , for a hazard ratio of 3.2 ( 95 % CI , 1.9 - 5.4 ) The 12-month cumulative incidence of major bleeding was 12.4 % ( 95 % CI , 6.5%-18.2 % ) in patients with cancer and 4.9 % ( 95 % CI , 2.5%-7.4 % ) in patients without cancer , for a hazard ratio of 2.2 ( 95 % CI , 1.2 - 4.1 ) . Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation . Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy . These risks correlate with the extent of cancer . Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed OBJECTIVE To prospect ively assess whether low-molecular-weight heparin ( LMWH ) provides a survival benefit in patients with advanced cancer . PATIENTS AND METHODS Between December 1998 and June 2001 , we performed a r and omized controlled study of patients with advanced cancer . Initially , the study was double blinded and placebo controlled , with the patients receiving daily injections of 5000 U of LMWH or saline . However , because of low accrual midway through the study , the placebo injection arm was eliminated , and the study became open labeled , with patients receiving either LMWH injections plus st and ard clinical care or st and ard clinical care alone . The primary study end point was overall survival . RESULTS Of 141 patients r and omized to this clinical trial , 3 dropped out , leaving 138 patients . The median survival time was 10.5 months ( 95 % confidence interval , 7.6 - 12.2 months ) for the combined st and ard care and placebo groups . The median survival time for the combined LMWH arms was 7.3 months ( 95 % confidence interval , 4.8 - 12.2 months ) . These median survival times were not significantly different ( log-rank P = .46 ) . The median survival times for the blinded and unblinded LMWH groups were 6.2 months and 9.0 months , respectively . The median survival times were 10.3 months for the blinded placebo arm and 10.5 months for the st and ard care arm . The rate of severe or life-threatening venous thromboembolism was 6 % in the LMWH arms and 7 % in the control arms . The rate of severe or life-threatening bleeding was 3 % in the LMWH arms and 7 % in the control arms Background . A positive influence of anticoagulant treatment in small cell lung cancer ( SCLC ) has been sug gested by experimental and clinical data BACKGROUND Small cell lung cancer ( SCLC ) is a chemotherapy-responsive tumor type but most patients ultimately experience disease progression . SCLC is associated with alterations in the coagulation system . The present r and omized clinical trial ( RCT ) was design ed to determine whether addition of low-molecular-weight heparin ( LMWH ) to combination chemotherapy ( CT ) would improve SCLC outcome compared with CT alone . METHODS Combination CT consisted of cyclophosphamide , epirubicine and vincristine ( CEV ) given at 3-weekly intervals for six cycles . Eighty-four patients were r and omized to receive either CT alone ( n = 42 ) or CT plus LMWH ( n = 42 ) . LMWH consisted of dalteparin given at a dose of 5000 U once daily during the 18 weeks of CT . Results Overall tumor response rates were 42.5 % with CT alone and 69.2 % with CT plus LMWH ( P = 0.07 ) . Median progression-free survival was 6.0 months with CT alone and 10.0 months with CT plus LMWH ( P = 0.01 ) . Median overall survival was 8.0 months with CT alone and 13.0 months with CT plus LMWH ( P = 0.01 ) . Similar improvement in survival with LMWH treatment occurred in patients with both limited and extensive disease stages . The risk of death in the CT + LMWH group relative to that in the CT group was 0.56 ( 95 % confidence interval 0.30 , 0.86 ) ( P = 0.012 by log rank test ) . Toxicity from the experimental treatment was minimal and there were no treatment-related deaths . CONCLUSIONS These results support the concept that anticoagulants , and particularly LMWH , may improve clinical outcomes in SCLC . Further clinical trials of this relatively non-toxic treatment approach are indicated PURPOSE Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival . In a double-blind study , we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism . METHODS Patients with metastasized or locally advanced solid tumors were r and omly assigned to receive a 6-week course of subcutaneous nadroparin or placebo . The primary efficacy analysis was based on time from r and om assignment to death . The primary safety outcome was major bleeding . RESULTS In total , 148 patients were allocated to nadroparin and 154 patients were allocated to placebo . Mean follow-up was 1 year . In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 ( 95 % CI , 0.59 to 0.96 ) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group . After adjustment for potential confounders , the treatment effect remained statistically significant . Major bleeding occurred in five ( 3 % ) of nadroparin-treated patients and in one ( 1 % ) of the placebo recipients ( P = .12 ) . In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment , the hazard ratio was 0.64 ( 95 % CI , 0.45 to 0.90 ) with a median survival of 15.4 and 9.4 months , respectively . For patients with a shorter life expectancy , the hazard ratio was 0.88 ( 95 % CI , 0.62 to 1.25 ) . CONCLUSION A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation PURPOSE In experimental systems , interference with coagulation can affect tumor biology . Furthermore , it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer . The primary aim of this study was to assess survival at 1 year of patients with advanced cancer . PATIENTS AND METHODS Patients with advanced malignancy ( N = 385 ) were r and omly assigned to receive either a once-daily subcutaneous injection of dalteparin ( 5,000 IU ) , a low molecular weight heparin , or placebo for 1 year . RESULTS The Kaplan-Meier survival estimates at 1 , 2 , and 3 years after r and omization for patients receiving dalteparin were 46 % , 27 % , and 21 % , respectively , compared with 41 % , 18 % , and 12 % , respectively , for patients receiving placebo ( P = .19 ) . In an analysis not specified a priori , survival was examined in a subgroup of patients ( dalteparin , n = 55 ; and placebo , n = 47 ) who had a better prognosis and who were alive 17 months after r and omization . In these patients , Kaplan-Meier survival estimates at 2 and 3 years from r and omization were significantly improved for patients receiving dalteparin versus placebo ( 78 % v 55 % and 60 % v 36 % , respectively , P = .03 ) . The rates of symptomatic venous thromboembolism were 2.4 % and 3.3 % for dalteparin and placebo , respectively , with bleeding rates of 4.7 % and 2.7 % , respectively . CONCLUSION Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy . However , the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology Gynecologic malignancies are often associated with deep vein thrombosis and pulmonary embolism , even before treatment is begun . But such complications also happen during treatment , also if thromboembolism prophylaxis is performed . The incidence of pulmonary embolism before treatment was investigated using scintigraphy . In a retrospective and in a prospect i ve r and omized trial , various methods of thromboembolism prophylaxis were evaluated during primary or postoperative radiation therapy . Pulmonary embolism was present in 11.9 % of the patients admitted with uterine malignancy . Retrospectively , there were deep vein thromboses in 6.8 % , pulmonary embolisms in 3.8 % and bleeding complications in 5.3 % of the patients receiving thromboembolism prophylaxis with acenocoumarol during radiation therapy of cervical and endometrial cancer . In the prospect i ve study , deep vein thromboses occurred in 1.5 % , pulmonary embolisms in 5.9 % and bleedings in 2.2 % , with both the LMW heparin and the acenocoumarol groups presenting similar results . Thromboembolism is a frequent paraneoplasia of uterine malignancies . The prevention of thromboembolic complications during radiation therapy of uterine malignancies is efficacious and safe using either LMW heparin or acenocoumarol |
562 | 27,821,641 | Ischaemic conditioning may reduce the rates of some secondary outcomes including stroke ( 18 trials ; 5995 participants ; 149 events ; risk ratio 0.72 , 0.52 to 1.00 ; P=0.048 ; very low quality evidence ) and acute kidney injury ( 36 trials ; 8493 participants ; 1443 events ; risk ratio 0.83 , 0.71 to 0.97 ; P=0.02 ; low quality evidence ) , although the benefits seem to be confined to non-surgical setting s and to mild episodes of acute kidney injury only .
CONCLUSIONS Ischaemic conditioning has no overall effect on the risk of death .
Possible effects on stroke and acute kidney injury are uncertain given method ological concerns and low event rates . | null | null |
563 | 27,400,651 | Conclusions In patients with malignant biliary jaundice requiring surgery , PBD group had significantly less major adverse effects than DS group .
Length of hospital stay and mortality rate were comparable in both the groups | Background In patients requiring surgical resection for malignant biliary jaundice , it is unclear if preoperative biliary drainage ( PBD ) would improve mortality and morbidity by restoration of biliary flow prior to operation .
This is a meta- analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice . | BACKGROUND The benefits of preoperative biliary drainage , which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head , are unclear . METHODS In this multicenter , r and omized trial , we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head . Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter ( 2.3 to 14.6 mg per deciliter ) were r and omly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks , followed by surgery , or surgery alone within 1 week after diagnosis . Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retro grade cholangiopancreatography . The primary outcome was the rate of serious complications within 120 days after r and omization . RESULTS We enrolled 202 patients ; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage ; 6 patients were excluded from the analysis . The rates of serious complications were 39 % ( 37 patients ) in the early-surgery group and 74 % ( 75 patients ) in the biliary-drainage group ( relative risk in the early-surgery group , 0.54 ; 95 % confidence interval [ CI ] , 0.41 to 0.71 ; P<0.001 ) . Preoperative biliary drainage was successful in 96 patients ( 94 % ) after one or more attempts , with complications in 47 patients ( 46 % ) . Surgery-related complications occurred in 35 patients ( 37 % ) in the early-surgery group and in 48 patients ( 47 % ) in the biliary-drainage group ( relative risk , 0.79 ; 95 % CI , 0.57 to 1.11 ; P=0.14 ) . Mortality and the length of hospital stay did not differ significantly between the two groups . CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications . ( Current Controlled Trials number , IS RCT N31939699 . BACKGROUND A preoperative biliary stent is commonly used after the initial evaluation of the patient with a periampullary mass . OBJECTIVE To evaluate the effect of a preoperative biliary stent on operative difficulty , postoperative complications , and length of hospital stay after a pancreatoduodenectomy . DESIGN A retrospective review of a prospect ively collected consecutive series . SETTING The Memorial Sloan-Kettering Cancer Center 's Surgical Service , New York , NY . PATIENTS AND METHODS Seventy-four patients underwent pancreatoduodenectomy between March 1 , 1994 , and February 15 , 1996 . Thirty-five did not receive a biliary stent , and 39 received a biliary stent prior to medical evaluation . We analyzed patient , nutritional , laboratory , and operating room factors . Univariate analysis was by Student t test , chi2 test , and Fisher exact test ; multivariate analysis was by logistic regression . Significance was defined at P<.05 . MAIN OUTCOME MEASURES Operative time , amount of blood loss , complications , and length of hospital stay . Wound complications were defined as cellulitis , superficial infections , and deep infections . Intra-abdominal complications were defined as intra-abdominal abscesses and pancreatic or biliary fistula . RESULTS Groups were equivalent for tumor size , risk of comorbidity , time spent in the operating room , and amount of blood loss . There was 1 perioperative death . Patients with a stent had significantly lower bilirubin ( P<.03 ) and aspartate aminotransferase ( P<.04 ) levels and a significantly increased risk of nodal positivity ( P<.05 ) . The patients with a biliary stent had an increased risk of wound or abdominal complications on univariate ( P<.003 ) and multivariate ( P<.02 ) analysis and tended toward a prolonged hospital stay ( P<.04 , Wilcoxon signed rank test ) . CONCLUSIONS A preoperative biliary stent was associated with an increased risk of wound or intra-abdominal complications ; a stent may prolong the length of hospital stay . However , length of time under anesthesia , amount of blood loss , and transfusion requirements were not altered . A biliary stent should be used with a high degree of selectivity in the management of patients with resectable periampullary masses OBJECTIVE To find out factors that may influence the mortality after Whipple 's operation , whether duct to mucosa anastomosis is better than classic " dunking " pancreaticojejunostomy and whether age over 70 is a contraindication for this procedure . DESIGN Prospect ively r and omised study . SETTING Teaching hospital , Taiwan , R.O.C. PATIENTS 93 patients with periampullary cancer undergoing Whipple 's operation were r and omly divided into two groups . Forty-six with periampullary cancer underwent invaginating pancreaticojejunostomy , and 47 patients underwent duct to mucosa anastomosis for reconstruction . MAIN OUTCOME MEASURES Mortality and morbidity were compared between two groups . RESULTS The over all mortality was 8 % ( 7/93 ) . An albumin concentration of less than 30 g/L before operation and operative blood loss influenced the surgical mortality both in the univariate and multivariate analysis . Age over 70 years was not a factor . Patients with duct to mucosa anastomoses had a leak rate of 4 % ( 2/47 ) , morbidity of 21 % ( 10/47 ) and mortality of 6 % ( 3/47 ) . Patients with an invaginated pancreaticojejunostomy had a leak rate of 15 % ( 7/46 ) , morbidity of 33 % ( 15/46 ) , and mortality of 9 % ( 4/46 ) . The need for total parenteral nutrition in the invaginated group ( 33 % ) was statistically greater than in the other group ( 11 % ) ( p = 0.01 ) . CONCLUSIONS The morbidity and mortality of pancreaticoduodenectomy for periampullary cancer although slightly greater for patients over the age of 70 are acceptable . The factors that may influence the mortality are an albumin concentration of less then 30 g/L and the amount of blood lost during operation . The duct to mucosa anastomosis is a safe procedure , which has a lower leak rate and less need for total parenteral nutrition than pancreaticojejunostomy 57 patients with obstructive jaundice were r and omly allocated to surgery with preoperative external biliary drainage ( 29 patients ) and without preoperative external biliary drainage ( 28 patients ) . 22 patients ultimately underwent laparotomy after a mean of 11.7 days of drainage and 25 had surgery without preoperative drainage . The postoperative complication rate was low and similar in both groups but complications associated with the drainage procedure were substantial . Perioperative mortality was 4/28 ( 14 % ) in the drainage group and 4/27 ( 15 % ) in the non-drainage group . There seems to be no advantage associated with routine preoperative external biliary drainage before surgery for obstructive jaundice OBJECTIVE To analyze the morbidity and mortality after radical and palliative pancreatic cancer surgery in Norway , especially the risk factors . SUMMARY BACKGROUND DATA A prospect i ve multicenter study between 1984 - 1987 including only histologically or cytologically verified adenocarcinoma of the pancreas ( N = 442 ) or the papilla of Vater ( N = 30 ) ; 84 patients ( 19 % ) with pancreatic carcinoma and 24 patients ( 80 % ) with papilla carcinoma underwent radical operations . A palliative procedure was performed in 252 patients ( 53 % ) . METHODS Clinical data , surgical procedures and the following morbidity and mortality were recorded on st and ardized forms . The risk factors were analyzed by a logistic multiple regression model . RESULTS The morbidity , reoperation , and mortality rates were 43 , 18 , and 11 % after radical surgery and 23 , 4 , and 14 % after palliative surgery . Karnofsky 's index was the sole independent risk factor for death after radical surgery . Splenectomy , age , and TNM stage influenced morbidity . Diabetes , Karnofsky 's index , and liver metastases were risk factors in palliative surgery . CONCLUSIONS The morbidity and mortality risks were comparable between total pancreatectomy and a Whipple 's procedure and between biliary and a double bypass . Preoperative biliary drainage had no impact on the risks and may be ab and oned . High age is a relative and a low Karnofsky 's index an absolute contraindication for radical surgery . Nonsurgical palliation of jaundice should be considered according to the presence of independent risk factors BACKGROUND Patients with obstructive jaundice undergoing surgical procedures have a significant risk of morbidity and mortality . The role of preoperative percutaneous transhepatic biliary drainage ( PTBD ) was evaluated in a r and omized trial . METHODS A total of 40 patients were assigned to either preoperative PTBD ( n = 20 ) , or surgery alone ( n = 20 ) . PTBD was performed under ultrasound guidance . There were no major complications related to the procedure . RESULTS Ultrasound guided drainage was a successful and safe method of preoperative biliary decompression . There was a marked relief from pruritus and significant reduction of hyperbilirubinaemia from a mean of 386.48 mumol/L to 116.10 mumol/L ( p < 0.001 ) . Mean duration of drainage was 42.5 days . Postoperative complications occurred in five patients in PTBD group ( 25 % ) compared to 11 patients ( 55 % ) in the control group . One death ( 5 % ) occurred in PTBD group compared to four deaths ( 20 % ) in the control group ( significant at 5 % level with probability 0.2 ) . CONCLUSIONS Ultrasound guided drainage is a useful preoperative supportive measure in preparing deeply jaundiced patients for surgery and permits hepatic function to return to a near normal state preoperatively . The improved results in our study were due to longer duration of drainage Thirty patients with obstructive jaundice with plasma bilirubin values greater than 200 mumol/L were r and omized at the time of percutaneous transhepatic Cholangiography to undergo immediate or delayed surgery . The patients who had preoperative percutaneous transhepatic biliary drainage ( PTBD ) for 13.8 + /- 5.8 days had fewer surgical complications than did patients who underwent immediate surgery ( p less than 0.02 ) , although when the complications of PTBD were included this advantage was diminished . Immediate surgery caused greater deterioration of renal function as measured by plasma urea , plasma B 2-microglobulin , phosphate clearance , uric acid clearance , and maximal concentrating ability than occurred after PTBD or delayed surgery . The improvement in phosphate clearance that followed PTBD was sustained through delayed surgical treatment , indicating better tubular function in these patients . This article supports the concept that preoperative PTBD will reduce surgical morbidity and will result in less renal impairment than will immediate surgery . However , the morbidity rates of the PTBD procedure will preclude its wide use It has been suggested that the placement of endoscopic or percutaneous biliary stents prior to pancreaticoduodenectomy increases postoperative morbidity . A retrospective review of a prospect ively collected data base was performed . Patients undergoing preoperative biliary stenting were compared with patients who did not undergo stenting . In addition , outcomes after endoscopic and percutaneous stenting were compared . Patients who had undergone operative biliary bypass prior to pancreaticoduodenectomy were excluded from the analysis . Between January 1994 and December 1997,567 patients underwent pancreaticoduodenectomy without prior operative biliaty bypass . Preoperative biliary stenting was performed in 408 patients ( 72 % ) , whereas the remaining 159 patients ( 28 % ) did not undergo biliary stenting . In the stented group , 64 % had stents placed via a percutaneous approach and 36 % had stents placed endoscopically . The stented patients were older ( mean 63.1 years vs. 61.4 years ; P = 0.05 ) and were more likely to be white ( 92 % vs. 82 % ; P = 0.005 ) . Those who had stents placed were more likely to have jaundice ( 67 % vs. 38 % ; P < 0.0001 ) and fever ( 5 % vs. 1 % ; P = 0.03 ) as presenting symptoms . There were no differences in multiple intraoperative parameters when the two groups were compared . Patients who had stems placed had a perioperative mortality rate of 1.7 % compared to 2.5 % in those who did not ( P = 0.3 ) . Although the overall complication rates were 3 5 % in those who had stents placed and 30 % in those who did not ( P = NS ) , patients with stems experienced a significantly increased incidence of pancreatic fistula ( 10 % vs. 4 % ; P = 0.02 ) and wound infection ( 10 % vs. 4 % ; P = 0.02 ) . The incidences of other postoperative complications were similar between the stented and unstented groups . Eight patients ( 3 % ) in the percutaneously stented group developed significant hemobilia after stent placement , whereas none of the patients undergoing endoscopic stent placement developed hemobilia ( P = 0.03 ) . There were no statistical differences in other complications between the percutaneously and endoscopically stented groups . Preoperative biliary stenting did not increase the overall complication rate or mortality rate in patients undergoing pancreaticoduodenectomy . Stenting does appear to increase the rate of pancreatic fismla formation , possibly as a result of pancreatic inflammation related to the stenting procedure . Stenting also increases the rate of wound infection , likely secondary to contaminated bile ( bactibilia ) after instrumentation of the biliary tree . Preoperative biliary stenting is safe but should be used selectively because of the above-mentioned risks . The method of stenting should be based on local expertise Fifty consecutive matched patients with benign or malignant biliary tract obstruction were compared to determine the efficacy of preoperative percutaneous biliary drainage ( PBD ) . Twenty-five patients underwent PBD for an average of nine days before operation ; 25 patients underwent percutaneous transhepatic cholangiography ( PTHC ) followed immediately by operation . Serum bilirubin levels before PTHC were 16.5 + /- 7.6 mg/dL and 14.9 + /- 7.6 mg/dL in PBD and non-PBD groups , respectively . Serum bilirubin levels decreased to 6.5 + /- 6.2 mg/dL preoperatively in patients having PBD . One week after operation , bilirubin levels were 4.2 + /- 4.3 mg/dL and 9.0 + /- 5.2 mg/dL in the PBD and non-PBD groups , respectively . Major morbidity ( sepsis , abscess , renal failure , or bleeding ) occurred in two patients ( 8 % ) having PBD and in 13 patients ( 52 % ) without PBD . One patient ( 4 % ) with PBD , and five patients ( 20 % ) without PBD , died . The mean hospital stay was shorter for the PBD group . Preoperative PBD reduces operative mortality and morbidity and results in a more rapid resolution of hyperbilirubinemia during the postoperative period The operative mortality for biliary tract obstruction due to malignancy is high . In 1981 a controlled clinical trial of pre‐operative percutaneous drainage was started at the Royal Postgraduate Medical School . At the time of percutaneous transhepatic cholangiography patients were r and omized either to laparotomy or to pre‐operative percutaneous transhepatic biliary drainage ( PTBD ) followed by laparotomy . Only patients with malignant biliary tract obstruction and serum bilirubin greater than 100 μmol/l were included . Seventy patients entered the trial , and five were withdrawn . Of the 65 remaining , 31 underwent laparotomy and 34 had pre‐operative PTBD followed by laparotomy . The median duration of drainage was 18 days and during this time the median bilirubin fell from 305 to 115 m̈mol/l . Five patients required early surgery for complications of PTBD and two died within 30 days of surgery . The mortality for laparotomy was 19 per cent ( 6/31 ) compared with 32 per cent ( 11/34 ) for drainage plus laparotomy . This trial highlights the hazards of PTBD in high risk patients and has failed to demonstrate a reduction in mortality with the use of pre‐operative PTBD BACKGROUND The indications for preoperative biliary stenting in patients with obstructive jaundice are controversial . We evaluated the effect of preoperative biliary stenting on bacterobilia and infectious complications following surgical treatment of proximal cholangiocarcinoma . DESIGN A retrospective review was performed of all patients undergoing surgical treatment of proximal cholangiocarcinoma . SETTING A metropolitan cancer surgery service . PATIENTS AND METHODS Seventy-one patients underwent palliative biliary bypass or curative resection of proximal cholangiocarcinoma from March 1 , 1991 , to April 1 , 1997 , and were entered into a prospect i ve data base . Forty-one patients underwent preoperative biliary intubation and stent placement . We analyzed patient , nutritional , laboratory , and operating room factors . Statistical evaluation was performed using Student t test and chi2 analysis . MAIN OUTCOME MEASURE Data were recorded for a history of cholangitis , operative time , amount of blood loss , incidence of intraoperative bacterobilia , proportion of patients with postoperative infectious and noninfectious complications , and length of hospital stay . RESULTS All patients ( n = 14 ) with a history of preoperative cholangitis had been subjected to previous endoscopic retro grade cholangiopancreatography and /or percutaneous transhepatic biliary drainage . Groups were equivalent for risk for comorbidity , proportion undergoing curative vs palliative procedures , time spent in the operating room , and amount of blood loss . Patients with stents had a significantly lower bilirubin level ( P = .005 ) . Patients with stents had a significantly increased risk for bacterobilia ( P = .001 ) and infectious complications ( P = .03 ) . Bacterobilia was present in 11 ( 100 % ) of 11 patients undergoing endoscopic stenting and in 15 ( 65 % ) of 23 patients undergoing percutaneous stenting . There was no increased risk for noninfectious complications , length of hospital stay , or mortality in patients with stents . In 10 ( 59 % ) of 17 patients with postoperative infectious complications and positive findings of intraoperative bile culture , the organism was synonymous . CONCLUSIONS Preoperative biliary stenting in proximal cholangiocarcinoma increases the incidence of contaminated bile and postoperative infectious complications . Endoscopic stents frequently do not relieve jaundice in high biliary obstruction and are rarely indicated , especially in light of their high contamination rate OBJECTIVES Whilst there are theoretical benefits from pre-operatively draining the biliary tree prior to pancreatoduodenectomy ( PD ) , the current literature does not support this intervention . The aim of this study was to explore the relationship between pre-operative stenting , bactibilia and outcome in a large United Kingdom tertiary referral practice . METHODS Patients undergoing PD were identified from a prospect ively maintained data base . The presence or absence of a stent prior to PD , and the results of bile cultures taken at PD were related to the subsequent post-operative course and the development of complications . RESULTS 280 patients underwent PD for periampullary malignancies , all of whom presented with jaundice . 118 patients were stented prior to referral ( 98 ERCP , 20 PTC ) . Bile cultures were positive more frequently in the stent group ( 83 % vs. 55 % ; p = 0.000002 ) and bactibilia was more common after ERCP than PTC ( 83 % vs. 56 % ; p = 0.006 ) . The overall prevalence of complications was 54 % in the stented and 41 % in the non-stented group ( p = 0.03 ) with statistical significance achieved for pancreatic leak ( p = 0.013 ) and haemorrhagic complications ( p = 0.03 ) . Comparing stent with no stent , there as no difference in the 30-day mortalities ( 8.5 % vs. 6.8 % ; p = 0.6 ) or the 1-year mortality rates ( 35 % vs. 28 % ; p = 0.21 ) . Mortality rates in the infection versus no infection groups were comparable at 30 days ( 8.5 % vs. 5.5 % ; p = 0.21 ) , and at 1 year ( 30.7 % vs. 26.4 % ; p = 0.25 ) . CONCLUSIONS Pre-operative stent insertion prior to PD is associated with increased morbidity but not mortality and this is greatest for stents placed at ERCP BACKGROUND The objective of this study was to identify whether the preoperative platelet-lymphocyte ( P/L ) ratio might improve the predictive value of CA19 - 9 levels in stratifying a patient group with suspected periampullary malignancy who do not require staging laparoscopy . METHODS Patients with suspected periampullary cancer were identified from a prospect ively maintained 10-year data base . Only patients with resectable disease who underwent staging laparoscopy and subsequent laparotomy were included . Low-risk groups were stratified using a CA19 - 9 cutoff value of < or = 150 kU/l ( or < or = 300 kU/l in patients with a concurrent bilirubin concentration > 35 micromol/l ) and a P/L ratio value of < or = 150 . RESULTS From 263 patients , preoperative CA19 - 9 levels and P/L ratios were available in 216 and 225 patients , respectively . The positive and negative predictive values for resectability , sensitivity , and specificity for CA19 - 9 levels < or = 150 kU/l were 83 % , 36 % , 51 % , and 73 % , respectively . For P/L ratios < or = 150 , these levels were 81 % , 38 % , 51 % , and 72 % , respectively . When combining the requirement for both CA19 - 9 levels and P/L ratios to be < or = 150 ( n = 38 out of 183 ) , both positive predictive value ( 95 % ) and specificity ( 96 % ) were improved ( Fisher exact test , P = .065 and P < .001 , respectively ) ; 21 % of laparoscopies were avoidable when using these criteria . Increasing T stage ( P = .005 ) , vascular invasion ( P < .001 ) , perineural invasion ( P = .008 ) , and resection margin involvement ( P < .001 ) were all associated with greater preoperative P/L ratios in resected periampullary adenocarcinoma ( n = 204 ) . CONCLUSIONS The preoperative P/L ratio reflects an index of tumor invasiveness and merits prospect i ve evaluation as an adjunct to CA19 - 9 in determining the requirement for laparoscopic staging in patients with potentially resectable periampullary malignancy A prospect i ve study of coagulation disturbances and endotoxemia in 42 patients having major pancreatic or biliary surgery was performed . Endotoxin , soluble fibrin , and fibrin degradation products were measured before and after operation in 28 patients with obstructive jaundice and in 14 nonjaundiced controls . In the control group there was one death and no unexplained fever or postoperative hemorrhage . The jaundiced group had more complications : seven deaths , nine episodes of fever , and six episodes of hemorrhage . Soluble fibrin was detected only in patients with obstructive jaundice , in whom it occurred in 38 percent before operation . Positive endotoxin assay was as common in control patients as in the jaundiced group , but in the latter endotoxin was associated ( p less than 0.05 ) with increased FDP and soluble fibrin . Patients with endotoxin or increased FDP levels before operation for jaundice carry a poor prognosis ( 7 of 11 died ) . Preoperative bowel preparation in 16 of the jaundiced patients did not affect the outcome To investigate and /or treat the causes of jaundice , 221 patients underwent the following procedures over 7 years : percutaneous transhepatic cholangiography ( PTC ) alone ( 104 patients ) , PTC with external biliary drainage ( 69 patients ) , or PTC with external/internal biliary drainage ( 48 patients ) . Forty-nine procedure-related complications occurred in 39 patients ( 18 % ) . Three patients ( 1.5 % ) required an emergency operation for hepatic hemorrhage ( 2 patients ) and a perforated gallbladder ( 1 patient ) . Two patients ( 1 % ) died as a direct result of the procedure secondary to hemorrhage ( 1 patient ) and sepsis ( 1 patient ) . Preoperative biliary decompression , although technically ( 95 % ) and physiologically ( 82 % ) successful in the majority of patients , had no therapeutic benefit when compared ( nonr and omized ) with those patients without alleviation of jaundice prior to surgical intervention |
564 | 16,465,173 | Contrary to previous review s that failed to distinguish between depressive symptoms and depression , this review found very little data from clinical trials ( without the possibility of confounding factors ) to demonstrate that psychotherapeutic interventions are effective in reducing depression in cancer patients .
A number of small-scale , single-centre trials indicated that psychotherapeutic interventions ( especially cognitive behavioural therapy ) can have effects on depressive symptoms in cancer patients . | Depression is common in cancer patients , and this often remains undetected and untreated .
Depression has been associated with poorer quality of life , in addition to increased impairment of immune response and poorer survival in cancer patients .
Previous systematic review s and meta-analyses of the efficacy of interventions for cancer patients with depression have failed to distinguish between caseness for depression and depressive symptoms . | BACKGROUND The psychological response to breast cancer , such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease , has been suggested as a prognostic factor with an influence on survival . We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer . METHODS 578 women with early-stage breast cancer were enrolled in a prospect i ve survival study . Psychological response was measured by the mental adjustment to cancer ( MAC ) scale , the Courtauld emotional control ( CEC ) scale , and the hospital anxiety and depression ( HAD ) scale 4 - 12 weeks and 12 months after diagnosis . The women were followed up for at least 5 years . Cox 's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response , with adjustment for known clinical factors associated with survival . FINDINGS At 5 years , 395 women were alive and without relapse , 50 were alive with relapse , and 133 had died . There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression ( hazard ratio 3.59 [ 95 % CI 1.39 - 9.24 ] ) . There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category ( 1.55 [ 1.07 - 2.25 ] ) . There were no significant results found for the category of " fighting spirit " . INTERPRETATION For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect . A high score for depression is linked to a significantly reduced chance of survival ; however , this result is based on a small number of patients and should be interpreted with caution Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients . A double‐blind placebo‐controlled study was therefore design ed to assess the effectiveness of 20 mg fluoxetine . Of 115 cancer patients who fulfilled entry criteria for levels of distress , 45 patients were r and omized to a fluoxetine treatment group ( FA ) and 46 patients to a placebo group ( PA ) after a 1‐week placebo period design ed to exclude placebo responders . The Montgomery and Asberg Depression Scale ( MADRS ) , the Hamilton Anxiety Scale ( HAS ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Revised Symptom Checklist ( SCL90‐R ) and the Spitzer Quality of Life Index ( SQOLI ) were used to assess the efficacy of fluoxetine . The response rate , defined by a HADS score lower than 8 after 5 weeks of treatment , was not significantly higher in the FA group ( 11 % ) compared to the PA group ( 7 % ) . Compared to the PA group , patients in the FA group showed a significantly greater decrease in SCL90‐R mean total score after 5 weeks , but not a greater decrease in HADS mean score . No difference between the two groups was found in observer‐reported assessment s ( MADRS , HAS and SQOLI ) . Significantly more drop‐outs were observed in the FA group ( n=15 ) than in the PA group ( n=7 ) , although the frequencies of side‐effects were not significantly different Cancer patients diagnosed with solid tumors and undergoing a first course of chemotherapy were r and omized to either conventional care or a 10 contact 20 week cognitive behavioral intervention design ed to reduce emotional distress . Three hypotheses were tested . First , a test for a group effect found that patients in the intervention who entered the trial with higher symptom severity reported significantly lower depression at 10 but not 20 weeks . Patients in the experimental group who entered with higher depression were more depressed at 10 weeks than patients in the control group . The second hypothesis compared the intervention in two sub-indices of symptom severity ; one comprised of symptoms with a depressive component , the other of symptoms not associated with depression . The intervention was more effective in lowering depression at 10 weeks through an interaction with the non-depressive symptom sub-index . At 20 weeks , a significant main effect for the intervention on depression was observed . No interaction with either sub-index was observed . The third hypothesis found no main or interaction effect between psychotropic drugs and the intervention . In conclusion , behavioral interventions may influence depression differently over time . Initially , the intervention lowered depression through certain symptoms and only later did it effect depression directly . Symptoms with an affective component are relatively unaffected by the intervention which was independent of the presence of psychotropic medications Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment Abstract Objective : To determine the efficacy of adjuvant psychological therapy in patients with testicular cancer and to compare the characteristics and psychosocial outcomes of men who agreed to participate with those who declined to participate in a r and omised trial of psychological intervention . Design : Newly diagnosed patients were asked to participate in a r and omised trial of psychological support compared with st and ard medical care . Participants and non- participants completed self assessment question naires at baseline and at 2 , 4 and 12 months . Setting : Testicular Tumour Unit of the Royal Marsden Hospital . Subjects : 73 of 184 ( 40 % ) eligible patients agreed to enter the r and omised trial ( participants ) and 81 ( 44 % ) declined to participate but agreed to complete further assessment s ( non- participants ) . 30 patients wanted no further contact with the research ers . Outcome measures : Hospital anxiety and depression scale , psychosocial adjustment to illness scale , Rotterdam symptom checklist , mental adjustment to cancer scale . Only scores on the hospital anxiety and depression scale are reported for evaluating treatment efficacy . Results : 111 of 184 ( 60 % ) eligible men declined to participate in the trial . Patients with stage I disease were most likely to refuse to participate . A patient was less likely to participate if he had low volume disease and was receiving no further treatment . Likelihood of participation was associated with stage of disease and with type of primary treatment ( P<0.001 for heterogeneity ) . Patients with early stage disease ( P<0.001 ) and fewer physical symptoms ( P<0.001 ) were less likely to participate . Psychosocial factors associated with participation included anxious preoccupation regarding disease ( P=0.01 ) . There were no differences in outcome between participants and non- participants during follow up . Patients seemed to gain little benefit from adjuvant psychological therapy . At 2 months change from baseline favoured the treated group in the anxiety subscale ( mean difference between groups −1.41 ( 95 % confidence interval −2.86 to 0.03 ) ) . This was not sustained when adjusted for factors related to the disease . By 12 months change from baseline seemed to favour the control group ( mean difference between groups 1.66 ( −0.18 to 3.50 ) ) . Conclusions : Patients with testicular cancer seem to have considerable coping abilities . Those who declined to participate in the trial differed from those who participated . Those who agreed to participate may comprise the clinical group who perceive a need for psychological support . No evidence was found to indicate a need for routinely offering adjuvant psychological therapy . Key messages Counselling for patients with cancer is widely advocated , although its effectiveness has not been fully evaluated No study of patients with cancer has evaluated a psychological intervention in young men or in a group of patients with a disease with an excellent prognosis Most patients with testicular cancer declined to participate in this r and omised trial of adjuvant psychological therapy , and those who participated had more psychosocial dysfunction No evidence of benefit was observed after treatment with adjuvant psychological therapy in this group of patients There were no consistently significant differences in psychosocial outcome over one year between those who agreed to participate and those who declined to BACKGROUND We conducted a r and omised , controlled trial of cognitive-existential group therapy ( CEGT ) for women with early stage breast cancer receiving adjuvant chemotherapy with the aim of improving mood and mental attitude to cancer . METHODS Women were r and omised to 20 sessions of weekly group therapy plus 3 relaxation classes or to a control arm receiving 3 relaxation classes . Assessment s , independently done at baseline , 6 and 12 months , included a structured psychiatric interview and vali date d question naires covering mood , attitudes to cancer , family relationships , and satisfaction with therapy . RESULTS Three hundred and three of 491 ( 62 % ) eligible patients participated over 3 years . Distress was high pre-intervention : 10 % were diagnosed as suffering from major depression , 27 % from minor depression and 9 % from anxiety disorders . On an intention-to-treat analysis , there was a trend for those receiving group therapy ( n=154 ) to have reduced anxiety ( p=0.05 , 2-sided ) compared to controls ( n=149 ) . Women in group therapy also showed a trend towards improved family functioning compared to controls ( p=0.07 , 2-sided ) . The women in the groups reported greater satisfaction with their therapy ( p<0.001 , 2-sided ) , appreciating the support and citing better coping , self-growth and increased knowledge about cancer and its treatment . They valued the CEGT therapy . Overall effect size for the group intervention was small ( d=0.25 ) , with cancer recurrence having a deleterious effect in three of the 19 therapy groups . Psychologists as a discipline achieved a moderate mean effect size ( d=0.52 ) . CONCLUSION CEGT is a useful adjuvant psychological therapy for women with early stage breast cancer . Interaction effects between group members and therapists are relevant to outcome . Group-as-a-whole effects are powerful , but the training and experience of the therapist is especially critical to an efficacious outcome Urinary and sexual dysfunctions are side effects of radical prostatectomy ( RP ) for prostate cancer ( PC ) that contribute to depression . Despite the effectiveness of support groups at reducing depression in cancer patients , men typically do not participate in them . The purpose of this pilot study was to test the effects of a dyadic intervention ( one-to-one support ) on social support ( Modified Inventory of Socially Supportive Behaviors ) , self-efficacy ( Stanford Inventory of Cancer Patient Adjustment ) , and depression ( Geriatric Depression Scale ) . Subjects were r and omized to group . Controls ( N=15 ; Mage=59.7 ) received usual care . Experimentals were paired with long-term survivors ( LTS ) who had RP and who had treatment side effects in common . Experimentals ( N=15 ; Mage=57.5 ) met with a LTS 8 times in 8 weeks to discuss concerns associated with survivorship . No significant differences were detected on social support , but after 4 weeks , significant differences were present on depression between controls and experimentals , however these differences were not seen at 8 weeks . After 8 weeks , there were also significant differences on self-efficacy between controls and experimentals . Weekly anecdotal data supported the feasibility and acceptance of the intervention that was a low cost strategy effective at reducing depression and increasing self-efficacy in men treated by RP . Future research directions and clinical application is presented Women with breast carcinoma commonly experience psychologic distress following their diagnosis . Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives . Web‐based breast cancer social support groups are widely used , but little is known of their effectiveness . Preliminary evidence suggests that women benefit from their participation in web‐based support groups Increasing numbers of women with breast cancer are seeking alternatives to st and ard group support in coping with their illness . This study examines outcomes for 181 women with breast cancer r and omized to either a 12-week st and ard group support or a 12-week complementary and alternative medicine ( CAM ) support intervention . Participants in the CAM group were taught the use of meditation , affirmation , imagery and ritual . The st and ard group combined cognitive-behavioral approaches with group sharing and support . Both interventions were found to be associated with improved quality of life ( CAM , P=0.008 ; St and ard , P=0.006 ) , decreased depression ( CAM , P=0.004 ; St and ard , P=0.02 ) , decreased anxiety ( CAM , P=0.0003 ; St and ard , P=0.02 ) and increased " spiritual well-being " ( CAM , P=002 ; St and ard , P=0.003 ) . Only the CAM group showed increases in measures of Spiritual Integration ( P=0.001 ) which were also significant between groups ( P=0.003 ) . The St and ard group was associated with decreased confusion ( P=0.01 ) and decreased helplessness/hopelessness ( P=0.01 ) , while the CAM group was associated with decreased avoidance ( P=0.01 ) . None of these latter changes were significant between groups . At baseline , very high correlations were noted between measures of quality of life , mood , and spiritual integration . At the end of the intervention , the CAM group showed higher satisfaction ( P=0.006 ) and fewer dropouts ( P=0.006 ) compared to the st and ard group . Better outcomes in quality of life in the CAM group were associated with lower initial fighting spirit ( r=-.39 , P=0.001 ) . No baseline factors predicted better outcomes in the St and ard group . In summary , the study found equivalence on most psychosocial outcomes between the two interventions PURPOSE Fatigue and depression typically occur together in cancer patients , suggesting a common etiology , perhaps based on serotonin . This r and omized clinical trial tested whether paroxetine , a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin , would reduce fatigue in cancer patients and whether any reduction was related to depression . PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue . Of 704 patients who reported fatigue at their second chemotherapy cycle , 549 patients were r and omly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks . The assessment s of fatigue and depression were performed at cycles 3 and 4 of chemotherapy . RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data . No difference was detected in fatigue between patient groups . At the end of the study , there was a difference between groups in the mean level of depression ( Center for Epidemiologic Studies Depression scores , 12.0 v 14.8 , respectively ; P < .01 ) . CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy . A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels BACKGROUND Depression has a reported mean prevalence of 24 % in patients diagnosed with cancer . However , little systematic research on the efficacy of antidepressants in patients with cancer has been performed . METHOD The efficacy and safety of mianserin were studied in 55 depressed women with breast cancer ( stage I or II and without known metastases ) , in a r and omised , double-blind , six-week , placebo-controlled study . RESULTS Statistically significant differences in the decrease in score from baseline on the Hamilton Rating Scale for Depression and the number of responders , favouring mianserin , were present after 28 and 42 days of treatment . Significantly more placebo-treated patients prematurely terminated the study due to lack of efficacy while the safety profile of mianserin was similar to that of placebo . CONCLUSIONS Treatment with mianserin result ed in a significant improvement in depressive symptoms in cancer patients , and was well tolerated PURPOSE / OBJECTIVES To test the effects of a computer-based nursing intervention design ed to provide patients and family caregivers with concrete , objective information on symptom management ; provide education about disease and treatment ; coordinate medical re sources ; and provide emotional support and counseling . DESIGN Two-site , r and omized clinical trial . SETTING S A large , urban , midwestern , tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city . SAMPLE 109 patients newly diagnosed with breast , colon , or lung cancer who were receiving chemotherapy ; 54 received st and ard care , and 55 participated in the intervention group . METHODS Outcome data were collected via structured telephone interviews at three time points : baseline , midway through the intervention , and one month postintervention . The intervention consisting of nine visits , five in person and four by telephone , was conducted over 18 weeks by advanced practice oncology nurses . MAIN RESEARCH VARIABLES Psychosocial functioning , anxiety , and depression . FINDINGS Patients who received the intervention had significantly less depression between baseline and the midway point , as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form . CONCLUSIONS Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment . Additional research is needed to underst and who benefited most from the intervention . IMPLICATION S FOR NURSING This nurse-directed intervention result ed in improved mental health for patients ; however , physical subscales were not changed . Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups . Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer PURPOSE This study was performed as part of a large depression screening project in cancer patients to determine the degree of physician recognition of levels of depressive symptoms in cancer patients and to describe patient characteristics that influence the accuracy of physician perception of depressive symptoms . METHODS Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care , Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12 oncologists . Subjects completed the Zung Self-Rating Depression Scale ( ZSDS ) and physicians were asked to rate their patients ' level of depressive symptoms , anxiety , and pain using numerical rating scales . Subjects ' sex , age , primary tumor type , medications , primary caregiver , and disease stage at diagnosis were also recorded . RESULTS Physician ratings of depression were significantly associated with their patients ' levels of endorsement of depressive symptoms on the ZSDS . However , agreement between physicians and patients is most frequently clustered when patients report little or no depressive symptoms . While physician ratings are concordant with patient endorsement of no significant depressive symptomatology 79 % of the time , they are only concordant 33 % and 13 % of the time in the mild-to-moderate/severe ranges , respectively . Physician ratings were most influenced by patient endorsement of frequent and obvious mood symptoms , ie , sadness , crying , and irritability . Physician ratings also appeared to be influenced by medical correlates of patients ' level of depressive symptoms ( functional status , stage of disease , and site of tumor ) . Additionally , patients whose depression was inaccurately classified reported significantly higher levels of pain and had higher levels of disability . Physicians ' ratings of depression were most highly correlated with physicians ' ratings of patients ' anxiety and pain . CONCLUSION Physicians ' perceptions of depressive symptoms in their patients are correlated with patient 's ratings , but there is a marked tendency to underestimate the level of depressive symptoms in patients who are more depressed . They are most influenced by symptoms such as crying and depressed mood , and medical factors that are useful , but not the most reliable , indicators of depression in this population . Physicians ' ratings of their patients ' distress symptoms seem to be global in nature -- they are highly correlated with anxiety , pain , and global dysfunction . Physician assessment might be improved if they were instructed to assess and probe for the more reliable cognitive symptoms such as anhedonia , guilt , suicidal thinking , and hopelessness . Screening instruments and the use of brief follow-up interviews would help to identify patients who are depressed PURPOSE To determine whether fluoxetine improves overall quality of life ( QOL ) in advanced cancer patients with symptoms of depression revealed by a simple survey . PATIENTS AND METHODS One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were r and omly assigned in a double-blinded fashion to receive either fluoxetine ( 20 mg daily ) or placebo for 12 weeks . Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression . Patients with recent exposure to antidepressants were excluded . RESULTS The groups were comparable at baseline in terms of age , sex , disease distribution , performance status , and level of depressive symptoms . One hundred twenty-nine patients ( 79 % ) completed at least one follow-up assessment . Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy-General , compared with patients given placebo ( P = .01 ) . Specifically , the level of depressive symptoms expressed was lower in patients treated with fluoxetine ( P = .0005 ) , and the subgroup of patients showing higher levels of depressive symptoms on the two- question screening survey were the most likely to benefit from treatment . CONCLUSION In this mix of patients with advanced cancer who had symptoms of depression as determined by a two- question bedside survey , use of fluoxetine was well tolerated , overall QOL was improved , and depressive symptoms were reduced PURPOSE To determine whether making patient-reported cancer needs , quality -of-life ( QOL ) , and psychosocial information available to the health care team , allowing coordinated specifically targeted psychosocial interventions , result ed in reduced cancer needs , improved QOL , and increased satisfaction with care received . METHODS Self-reported cancer needs , QOL , and psychosocial information was collected from 450 people with cancer , using st and ardized question naires via a touch-screen computer . For a r and omly chosen two thirds , this information was made available to the health care team who coordinated targeted psychosocial interventions . Information from the remaining one third was not seen . Patients were assessed 2 and 6 months after r and omization for changes in their cancer needs , QOL , and psychosocial functioning and satisfaction with overall care received . RESULTS There were no significant differences between the two arms with respect to changes in cancer needs , QOL , or psychosocial functioning between the baseline and follow-up assessment s , nor with respect to satisfaction with care . However , for the subgroup of patients who were moderately or severely depressed at baseline , there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment ( P = .001 ) . CONCLUSION Making patient-reported cancer needs , QOL , and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL , psychosocial functioning , or satisfaction with the care received . However , identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression PURPOSE / OBJECTIVES To test the value of telephone-administered cognitive-behavioral therapy in a study of patients with breast cancer . DESIGN Women were assigned r and omly to a therapy group or an assessment -only control group . SETTING A tertiary cancer treatment center serving rural areas of North Dakota and Minnesota . SAMPLE Women were recruited within three to four months of stage I ( n = 27 ) or stage II ( n = 26 ) breast cancer diagnosis . Age ranged from 30 - 82 ( mean = 51.5 years ) . Most participants ( n = 35 ) underwent a modified radical mastectomy ; 17 underwent a lumpectomy . METHODS Therapy involved 10 30-minute ( or less ) telephone sessions . Data that were collected from mailed question naires included psychological distress ( Profile of Mood States ) , perceived stress , coping ( Coping Response Indices-Revised ) , quality of life ( Medical Outcome Scale ) , and satisfaction with therapy . Measures were completed at baseline and at 4- and 10-month follow-up intervals . MAIN RESEARCH VARIABLES Telephone therapy , stress , coping , and quality of life . FINDINGS With time , women in the therapy and control groups reported reduced stress and improved quality of life . However , significant reductions in some kinds of distress ( anxiety , anger , depression , and confusion ) were not observed . Most therapy participants liked the telephone treatment sessions but showed only modest improvement ( less anxiety and confusion ) compared with women in the control group . CONCLUSIONS Most patients reported being comfortable with the telephone therapy and said that they felt better as a result of it . However , the outcome data showed that telephone therapy -- as carried out in this study --produced only modest benefits . Research ers need to consider who is best for delivering such therapy . IMPLICATION S FOR NURSING PRACTICE Providing telephone therapy to patients with breast cancer has potential benefits , and nurses may be the appropriate professionals to administer the therapy BACKGROUND This study was conducted to determine the efficacy and tolerability of fluoxetine and desipramine in treating depressive symptoms in women with cancer . METHOD In this prospect i ve , 6-week , double-blind , placebo-controlled trial , we compared fluoxetine with desipramine in treating depressive symptoms in 40 women diagnosed with cancer . Scales used to measure efficacy and tolerability were the Hamilton Depression Rating Scale ( HAM-D ) , the Hamilton Anxiety Rating Scale ( HAM-A ) , the Clinical and Patient 's Global Impression ( CGI and PGI ) scales , the Functional Living Index for Cancer ( FLIC ) , the Memorial Pain Assessment Card ( MPAC ) , and the SF-36 Health Survey . RESULTS Fluoxetine and desipramine treatments improved depression and anxiety symptoms . There was a trend towards significance in improvement of FLIC scores ( as evidence d by greater numerical improvements with fluoxetine treatment ) . Fluoxetine treatment alone was associated with statistically significant improvements in MPAC Mood scale scores . Both treatments showed statistically significant improvements in the quality of life SF-36 scores in Role Emotional , Social Functioning , Mental Health , and Vitality . CONCLUSIONS Both fluoxetine and desipramine were effective and well-tolerated in improving depressive symptoms and quality of life in women with advanced cancer . Fluoxetine may offer greater benefit to these patients , as evidence d by greater improvements in fluoxetine-treated patients on several quality of life measures . Our results , while meaningful , should be confirmed in a larger patients sample . However , experience from studies of antidepressant use in patients with advanced cancer has shown that intercurrent disease and treatment variables make it difficult to conduct large studies Abstract Objective : To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer . Design : Prospect i ve r and omised study . Setting : Three teaching hospitals in Glasgow with established breast clinics . Subjects : 272 women aged less than 70 years undergoing surgery for breast cancer . Interventions : Patients were r and omly allocated to receive routine care from ward staff , routine care plus support from breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation . Main outcome measures : Prevalence of psychological morbidity as assessed by self rating scales : 28 item general health question naire and its subscales , and hospital anxiety and depression scale . Measurements were made at first postoperative clinic visit and at three , six , and 12 months after surgery . Results : On each self rating scale , psychological morbidity tended to fall over the 12 month period . For each scale , scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other . Differences were significant or nearly so : P values were 0.015 ( 28 item general health question naire ) , 0.027 ( anxiety and insomnia ) , 0.072 ( severe depression ) , 0.053 ( somatic symptoms ) , 0.031 ( social dysfunction ) , 0.093 ( hospital anxiety ) , and 0.003 ( hospital depression ) . Conclusion : Support from breast care nurse can significantly reduce psychological morbidity , as measured by self rating scales , in women undergoing breast cancer surgery . Key messages Key messages The value of different forms of psychological support for breast cancer patients is uncertain We compared effect of four different types of support for patients undergoing surgery for breast cancer : routine care from ward staff , routine care plus support from specialist breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation Scores of psychological morbidity were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other Psychological support from an experienced breast care nurse can reduce psychological morbidity in patients undergoing surgery for breast To the authors ' knowledge , there had been no evidence for the efficacy of psychosocial intervention among Japanese cancer patients . The objective of this study was to determine the effect of a psychosocial group intervention in reducing psychologic distress and enhancing coping in this population in a r and omized controlled trial When one member of a couple develops a serious illness , the lives of both partners are likely to be affected . Interventions directed at both partners are generally lacking , however . In the present study , a brief counseling program directed at couples confronted with cancer was evaluated . The intervention focused mainly on the exchange of social support and help between both partners and was aim ed at restoring perceptions of equity . Couples were r and omly assigned to an experimental group or a waiting-list group . After the intervention , both patients and their partners reported lower levels of perceptions of underinvestment and overbenefit , and higher levels of relationship quality . Moreover , among patients psychological distress decreased after the intervention . These effects were generally maintained until follow-up three months later . Associations between perceptions of equity and relationship quality and psychological distress were also examined Many studies have reported that cancer patients who show difficulties maintaining perceptions of control report more psychological distress than patients who are higher in control . Besides perceptions of control , feelings of illness uncertainty have also been regarded as a predictor of psychological distress . Given these strong relationships between perceptions of low control and high illness uncertainty and psychological distress , the present study examined whether an informational self-management intervention ( booklet ) could moderate this relationship . The booklet contained general and specific information about cancer and cancer treatment , information about possible coping strategies , and social comparison information , which consisted of short stories of other patients . Prior to radiotherapy , 209 patients with cancer completed baseline measures , including control and illness uncertainty . After completing radiotherapy , patients were r and omly allocated to receive either a booklet ( experimental group ; N=103 ) or no booklet ( control group ; N=106 ) . Three months after the intervention , aspects of psychological distress were assessed , including tension , anger , depression , fatigue and vigour . The results supported our hypotheses and suggested that a self-management intervention is relevant in reducing the relationship between control and illness uncertainty before radiotherapy and psychological distress after radiotherapy . This seems important , especially for high-risk patients who perceive little control and much illness uncertainty Objective To examine the effect of counselling and relaxation intervention on psychological symptoms in patients with gynaecological cancer between the post‐operative period and the six‐week review Although many studies have documented patterns of emotional distress in persons undergoing radiation treatment for cancer , there have been few controlled evaluations of counseling or psychotherapy outcomes with these persons . In this research , the effects of cognitive-behavioral and socially supportive group therapy were evaluated . A total of 72 depressed cancer patients were r and omly assigned to one of three conditions -- cognitive-behavioral treatment , social support , or a no-treatment control condition . Before and after intervention and at 6-month followup , study participants were individually assessed by using measures of symptom distress . Relative to the comparison group , both the cognitive-behavioral and social support therapies result ed in less depression , hostility , and somatization . The social support intervention also result ed in fewer psychiatric symptoms and reduced maladaptive interpersonal sensitivity and anxiety . It was concluded that both group therapies can reduce symptoms of distress for depressed persons undergoing radiation treatment for cancer . Both forms of therapy result ed in improvements in psychosocial function ( compared with no treatment at all ) , but social support groups demonstrated more changes that were evident at 6-month followup . Further research is needed to evaluate the differential effectiveness of mental health services provided to cancer patients undergoing radiation BACKGROUND Depression commonly complicates treatment with the cytokine interferon alfa-2b . Laboratory animals pretreated with antidepressants have less severe depression-like symptoms after the administration of a cytokine . We sought to determine whether a similar strategy would be effective in humans . METHODS In a double-blind study of 40 patients with malignant melanoma who were eligible for high-dose interferon alfa therapy , we r and omly assigned 20 patients to receive the antidepressant paroxetine and 20 to receive placebo . The treatment was begun 2 weeks before the initiation of interferon alfa and continued for the first 12 weeks of interferon alfa therapy . RESULTS During the first 12 weeks of interferon alfa therapy , symptoms consistent with a diagnosis of major depression developed in 2 of 18 patients in the paroxetine group ( 11 percent ) and 9 of 20 patients in the placebo group ( 45 percent ) ( relative risk , 0.24 ; 95 percent confidence interval , 0.08 to 0.93 ) . Severe depression necessitated the discontinuation of interferon alfa before 12 weeks in 1 of the 20 patients in the paroxetine group ( 5 percent ) , as compared with 7 patients in the placebo group ( 35 percent ) ( relative risk , 0.14 ; 95 percent confidence interval , 0.05 to 0.85 ) . The incidence of adverse events was similar in the two groups . CONCLUSIONS In patients with malignant melanoma , pretreatment with paroxetine appears to be an effective strategy for minimizing depression induced by interferon alfa |
565 | 18,216,743 | Preoperative fatigue severity scores and improvement noted after surgery were similar to the respective values for other pooled CRS symptoms | BACKGROUND Fatigue is a common symptom of chronic rhinosinusitis ( CRS ) , yet the response of fatigue to endoscopic sinus surgery ( ESS ) has not been systematic ally evaluated . | OBJECTIVE To implore the positive effects of endoscopic sinus surgery on the symptoms and quality of life ( QOL ) of patients with chronic rhinosinusitis ( CRS ) and their changing regularity of symptoms and QOL . METHODS A prospect i ve , r and omized and controlled trial was conducted to survey symptoms and QOL status of 120 CRS patients undergoing endoscopic sinus surgery , in contrast to that of 200 healthy individuals passing health examination , at the baseline and at 3- and 6-months postoperatively by visual analog score ( VAS ) symptom instrument and QOL instruments including medical outcome study short-form 36-items health survey ( SF-36 ) and sino-nasal outcome test-20 ( SNOT-20 ) . RESULTS In the 3 months follow-up setting s , total of individual symptom severity scores and global symptom severity scores of VAS , such domains as role physical and general health of SF-36 and total of the 20 items scores and the most important 5-item scores of SNOT-20 all began to get better markedly ( P < 0.05 ) ; in the 3 - 6 months follow-up setting s , the indices above stayed fixed ( P > 0.05 ) ; and in the 6-months follow-up setting s , indices of symptoms and QOL status entirely improved from the baseline , with SF-36 showing no scoring difference between CRS patients and healthy individuals , whereas VAS showed that abnormal nasal drainage and decreased sense of smell were still left and SNOT-20 showed that abnormal nasal drainage and lack of good sleep left , inferior to that of healthy objects significantly ( P < 0.05 ) . CONCLUSIONS On the whole CRS patients undergoing endoscopic sinus surgery recover symptomatically and come back to normal level of QOL status at the 6 months postoperatively , but such significant problems as abnormal nasal drainage , decreased sense of smell and lack of good sleep still remain and need to be treated Background Chronic rhinosinusitis ( CRS ) is a common disease that has a significant impact on quality of life ( QOL ) . The aim of this study was to evaluate the longer-term effects of combined medical and surgical therapy for CRS on overall health status and QOL . Methods We used a prospect i ve study that utilized the Short-Form 36 Survey at baseline presentation and at a mean time of 3 years post-functional endoscopic sinus surgery to assess the general health status of patients who presented for their initial visit from 1996 to 1998 . Of the 200 r and omly selected patients , 150 respondents completed follow-up surveys ( a 75 % response rate ) . Results Eighty-nine ( 59.3 % ) women and 61 ( 40.7 % ) men were included in the study . Baseline QOL scores indicated significant differences between patients with CRS and published norms in 6/8 subscale parameters ( role physical , bodily pain , general health , social function , vitality , and mental health ) . Significant improvement in all six categories was maintained at the end of the study period ( p < 0.05 ) with QOL scores within limits of published norms for the general population . Conclusion Our data indicate that functional endoscopic sinus surgery , combined with appropriate postoperative care , is effective at maintaining a significant improvement in the overall general health status of patients for at least 3 years after surgical intervention and that the overall scores return to a range of normative values for the general population OBJECTIVE The objective of this study was to determine if endoscopic sinus surgery ( ESS ) is effective in the management of chronic recurrent rhinosinusitis ( CRRS ) . METHODS A consecutive series of patients with CRRS diagnosed according to stringent criteria was prospect ively examined before and at least 1 year after ESS . Paranasal sinus computed tomography scans were staged and ESS was performed targeting radiographic disease and the ostiomeatal complex . Preoperative and postoperative disease severities in terms of symptom scores , medicine utilization , and re source factors were assessed using the rhinosinusitis symptom inventory ( RSI ) . Improvements in RSI symptom domains , medical and economic re source factors were determined using effect sizes and statistical comparison before and after ESS . RESULTS Nineteen patients ( mean age , 42.3 years ) completed the study with a mean follow up of 19.1 months . The mean Lund score was 3.42 ( st and ard deviation , 4.09 ) . Statistically significant decreases in nasal ( -36.1 ) , facial ( -28.4 ) , oropharyngeal ( -34.6 ) , systemic ( -24.7 ) , and total ( -31.9 ) RSI symptom domain scores were observed ( all P < .003 ) with effect sizes ranging from 0.87 to 1.63 ( strong surgical effect ) . Statistically significant decreases in antihistamine use ( -30 % , P = .031 ) , number of workdays missed as a result of CRRS ( -1.9 , P = .035 ) , and number of acute infectious episodes ( -2.5 , P = .006 ) were also observed . However , declines in weeks of antibiotic use ( -2.8 weeks , P = .293 ) and number of antibiotic courses ( -1.7 , P = .118 ) were not significant . CONCLUSIONS Patients with CRRS may substantially benefit both symptomatically and medically from ESS . Although surgery should be used cautiously in treating CRRS , further trials of ESS for CRRS are warranted BACKGROUND Chronic rhinosinusitis affects millions of North Americans and has been increasing annually since 1991 . This study aim ed to evaluate the effectiveness of functional endoscopic sinus surgery ( FESS ) done with the use of computer assistance ( CASS ) and without the use of computer assistance on patient quality of life . As of this writing , there is no published study that measures the difference in patient quality of life with and without image guidance in endoscopic sinus surgery . METHODS A nonr and omized prospect i ve study was performed on 95 patients . A 31-item quality of life ( Rhinosinusitis Outcome Measures Form [ RSOM-31 ] ) question naire was administered to patients prior to surgery and 6 months following surgery during a 3-year enrollment period . Patients assessed both rhinologic and nonrhinologic symptoms using a statistically vali date d scoring system . Statistical analysis was performed using both equal and unequal variance sample t-tests when appropriate . RESULTS Statistically significant improvement in mean score analysis between preoperative and postoperative results for all symptom subgroups was reported when the entire study population was included . When the improvement in quality of life was compared between the CASS and FESS surgical groups , the CASS group demonstrated an overall greater improvement in quality of life . CONCLUSION Quality of life restrictions in patients with chronic rhinosinusitis were greatest in the areas of nasal symptoms and sleep deprivation , which were significantly improved by endoscopic sinus surgery . Although the long-term effect of CASS as measured by patient quality of life remains relatively unknown , there appears to be a significant trend indicating greater quality of life improvement in the short- term over non-computer-assisted FESS techniques OBJECTIVE To evaluate the prevalence and severity of individual Rhinosinusitis Task Force ( RSTF ) symptoms in patients with chronic rhinosinusitis ( CRS ) undergoing functional endoscopic sinus surgery ( FESS ) . METHODS Retrospective analysis of prospect ively collected data in 201 patients treated with FESS . The prevalence and severity of individual RSTF major and minor symptom scores grade d on a visual analogue scale ( VAS ) were compared . Correlation between absolute improvement in individual symptom scores at 1-year postoperative was performed . RESULTS One-hundred fifty-eight of 201 patients met inclusion criteria giving a response rate of 78 % . The average age was 49.4 ( range 18 - 80 ) with a male-to-female ratio of 1.1:1 . The preoperative leading mean symptom scores were postnasal drip ( 5.8 + /- 0.3 ) , nasal obstruction ( 5.7 + /- 0.3 ) , and facial congestion ( 5.1 + /- 0.3 ) . These symptoms were also the most prevalent with 82 % , 84 % , and 79 % of patients reporting these symptoms , respectively . Postoperative symptom improvements were significant ( P < .0001 ) across all RSTF domains except fever . The highest percentage improvement was seen with facial congestion ( 93 % ) , nasal obstruction ( 92 % ) , and postnasal drip ( 85 % ) . Multivariate analysis revealed significant ( P < .0001 ) high correlation between improvements of facial pain/pressure with facial congestion ( R = 0.72 ) , facial congestion with nasal obstruction ( R = 0.65 ) , and facial pain/pressure with headache ( R = 0.72 ) . CONCLUSION The top three RSTF symptoms were postnasal drip , nasal obstruction , and facial congestion in terms of prevalence and severity . Symptom scores improved after FESS . Of these symptoms , the degree of improvement of facial pain/pressure , facial congestion , nasal obstruction , and headache are highly correlated OBJECTIVES /HYPOTHESIS The objectives of this prospect i ve , double-blind diagnostic cohort study were to explore the relationship between patients ' reported symptoms of chronic rhinosinusitis ( CRS ) and radiographic findings in CRS to define clinical ly based diagnostic criteria for CRS and to determine a classification scheme that would allow for the accurate diagnosis of patients with CRS . METHODS A prospect i ve series of adult patients undergoing evaluation for potential chronic rhinosinusitis was studied . Patients ' symptoms were tabulated with the Rhinosinusitis Symptom Inventory ( RSI ) , which records symptoms associated with CRS on a Likert scale ( 5 = maximally severe ) . Medication and re source utilization were also tabulated . Scores for nasal , facial , oropharyngeal , systemic , and total symptom domains were computed ( 100 = maximum severity ) . Concurrent paranasal sinus computed tomography was obtained for each patient and scored according to the Lund-McKay system with review er blinding . Patients were classified as normal or representing true CRS according to previously published diagnostic radiographic criteria under two analyses . In analysis 1 , Lund scores < or = 1 were considered nondiseased and scores > or = 2 were considered as representing true CRS . In analysis 2 , Lund scores < or = 3 represented normal and scores > or = 4 represented true CRS . For each analysis , univariate statistics were computed to determine differences among patients ' reported symptoms with and without true CRS . Subsequently , classification analysis using classification regression trees was conducted to determine heuristics among clinical ly based criteria for the diagnosis of CRS . RESULTS Seven hundred three adult patients were enrolled ( mean age , 43.1 years ) . The most commonly reported symptoms in order of decreasing severity and presence were nasal obstruction , nasal congestion , discharge , fatigue , headache , facial pressure , and dysosmia , all with mean severity scores > or = 2.0 . Patients were previously treated for approximately 3 months each with topical nasal steroids , oral antihistamines , and oral antibiotics . Patients missed substantial workdays ( mean , 3.8/year ) and incurred significant physician visits ( mean , 3.5/year ) as a result of CRS . The nasal symptom domain exhibited the greatest severity ( 51.8 ) followed closely by the facial symptom domain ( 47.3 ) . According to the analysis 1 , 144 ( 20.5 % ) patients were classified as normal and 559 ( 79.5 % ) as true CRS . Only the presence of polyps ( P < .001 ) and dysosmia ( P = .008 ) distinguished between normal and diseased patients ; there were no significant differences between groups for the other symptoms and RSI domains . Classification analysis revealed that the presence of polyps , absence of dental pain , and low congestion/obstruction scores in the presence of dental pain predicted true CRS . Finally , a history of extended antibiotic courses before presentation also predicted true CRS . In the second analysis , 243 ( 34.6 % ) were normal versus 460 ( 65.4 % ) with true CRS . Only polyp presence and dysosmia exhibited statistically significant differences between normal and diseased patients ( P < .001 ) . The mean RSI nasal domain was higher for true patients with CRS ( P = .01 ) . Classification analysis identified polyp presence and dysosmia score > 2 effectively predicted CRS . Fatigue < or = 2 , discharge < or = 4 , and obstruction < or = 3 further predicted for CRS . Symptoms despite a > or = 5.5-week trial of nasal steroids also predicted CRS . Other major and minor symptoms , RSI domains , and re source factors failed to influence diagnostic classification . CONCLUSIONS The diagnosis of CRS based on symptom criteria is difficult because most symptoms ( other than dysosmia ) do not distinguish between radiographically normal and diseased patients . A classification scheme for CRS based on the presence or absence of polyps is valid . It is possible to classify patients with true CRS based on symptoms , but this requires complicated heuristics . Corroborating radiographic evidence should be required to establish the diagnosis of CRS before long periods of therapy or surgical intervention OBJECTIVE To determine whether preoperative computed tomography ( CT ) stage predicts degree of symptom improvement after endoscopic sinus surgery ( ESS ) . METHODS A series of adult patients undergoing ESS was prospect ively evaluated with CT and the rhinosinusitis symptom inventory ( RSI ) preoperatively and at a minimum of 12 months postoperatively . Symptom domains ( nasal , facial , oropharyngeal , systemic , and total ) were computed and both absolute change and percentage change in symptom domain scores before and after ESS were correlated with the preoperative CT scan stage according to three staging systems : Lund-MacKay , Kennedy , and Harvard . RESULTS One-hundred sixty-one patients ( mean age , 40.2 years ) completed the study with a mean follow-up of 19.4 months . Overall , statistically significant decreases in RSI symptom domains were noted for the nasal ( net change -30.1 [ range -100 to + 100 ] ) , facial ( -26.1 ) , oropharyngeal ( -13.4 ) , systemic ( -17.0 ) , and total ( -20.8 ) symptom scores ( all P < .001 ) . For the absolute change in total symptom score , no statistically significant correlation with CT stage was demonstrated for any of the staging systems ( Lund : Spearman rho = -0.004 , P = .962 ; Kennedy : rho = -0.008 , P = .918 ; Harvard : rho = -0.011 , P= .891 ) . Similarly , no significant correlation with CT stage was demonstrated with the other symptom domains . Additionally , no significant correlation was identified between preoperative CT stage and percentage change in symptom domain scores . CONCLUSIONS Although CT scan is widely accepted as an accurate diagnostic tool for chronic rhinosinusitis , CT scan stage alone does not significantly predict symptom outcomes after chronic rhinosinusitis , regardless of staging system utilized BACKGROUND The negative effect of chronic rhinosinusitis on patient quality of life has been generally underappreciated and undervalued . So far , only a few studies have examined health-related quality of life at German language patient collectives with vali date d measuring instruments . PATIENTS AND METHODS Preoperatively , 163 patients were included into the study . Three months and 1 year after functional endonasal sinus surgery 123 and 82 patients , respectively , participated in the question ing . To measure health-related quality of life , we used version 20 of the German Adapted Version of the Sinonasal Outcome Test and the Short Form 36 Health Survey ( SF-36 ) . The German normative values of the SF-36 were used for analysis . RESULTS Postoperatively , a significant improvement in health-related quality of life was determined on all scales of both measuring instruments . Comparing our data with the German normative values of the SF-36 , we found a lasting approximation of the average assessment levels in seven of eight scales . CONCLUSION Functional endonasal sinus surgery leads to significant improvements in disease-specific and general quality of life in patients with chronic rhinosinusitis Background The aim of this study was to evaluate the impact of gender on health-related quality of life ( HRQOL ) in patients with chronic sinusitis Methods A prospect ively administered survey was performed . For measuring HRQOL , we used the German versions of the Short Form 36 ( SF-36 ; eight subscales ) and the European Quality of Life—5 Dimensions ( EQ-5D ) ( two subscales ) . For all SF-36 subscales we used norm-based scoring of the general German population . Results One hundred twenty-three patients ( 45 women and 78 men ) underwent HRQOL evaluation at baseline ( preoperatively ) and 3 months after endonasal sinus surgery . Compared with male patients , female patients scored a significantly worse baseline in all SF-36 and one EQ-5D subscales and 3 months later in only one SF-36 subscale . Compared with the norm-based scores , both women 's and men 's SF-36 scores reached normal levels in seven subscales after 3 months . Conclusion Compared with men , women assessed preoperative HRQOL as being worse . Most women 's and men 's SF-36 subscales reached normal levels at the 3-month follow-up OBJECTIVE To determine the effectiveness of endoscopic sinus surgery ( ESS ) for individual symptoms , medication use , and related factors in patients with chronic rhinosinusitis ( CRS ) . DESIGN Nonr and omized , prospect i ve , clinical trial . INTERVENTIONS Adult patients with medically refractory CRS were examined before ESS with the Rhinosinusitis Symptom Inventory to catalog major and minor symptoms , medication use , physician visits , and missed workdays due to CRS . After a minimum 6-month follow-up after ESS , patients were examined to determine response to therapy . After computation of Rhinosinusitis Symptom Inventory domains , comparisons were conducted and effect sizes were computed for the change in symptoms after surgery . RESULTS One hundred adults completed the examination , with a mean follow-up of 19.0 months . Before surgery , the mean major symptom scores ranged from 2.5 to 3.5 ( Likert scale , from 0 [ symptom absent ] to 5 [ maximum severity ] ) and the minor symptom scores ranged from 0.8 to 2.8 . After surgery , statistically significant decreases in major and minor symptoms were noted ( P<.001 for all ) . The largest effect sizes were noted for the decreases in facial pressure , congestion , nasal obstruction , rhinorrhea , and headache ( absolute value of effect size > 0.85 for all ) . Similarly , large effect sizes were noted for decreases in symptoms in the nasal ( -1.30 ) , facial ( -1.13 ) , and total ( -1.25 ) symptom domains of the Rhinosinusitis Symptom Inventory . Medication use actually increased for topical nasal corticosteroids , but decreased for prescription antihistamines . A mean reduction of 1.1 antibiotic courses ( mean decrease of 2.3 weeks taking antibiotics ) was noted after ESS . CONCLUSIONS Endoscopic sinus surgery provides significant symptom relief for the nasal and facial symptoms associated with CRS . Patients will often still require topical nasal corticosteroids for the management of their CRS , but can expect decreases in antibiotic requirements after ESS OBJECTIVE /HYPOTHESIS To assess the validity and responsiveness of a new health-related quality of life ( HRQL ) instrument for patients with chronic sinusitis . STUDY DESIGN Prospect i ve case series . METHODS Patients with chronic sinusitis undergoing endoscopic sinus surgery were assessed in two otolaryngology practice s affiliated with an academic hospital . Patient-reported HRQL was assessed using a new instrument ( includes symptom frequency , bothersomeness , and impact scales ) , the Chronic Sinusitis Survey ( CSS ) , and the generic SF-12 at baseline and 3 months postsurgery . The psychometric properties of the new instrument were assessed including reliability , validity , responsiveness , and interpretability . RESULTS Among 50 enrolled patients , 49 underwent surgery and 39 ( 80 % ) completed 3-month follow-up . Internal consistency was high for the symptom impact scale . The symptom frequency and , especially , bothersomeness scales had lower internal consistency and were comparable with the CSS . Correlation analyses support the construct validity of the new measure compared with the CSS and SF-12 . The responsiveness of the new instrument was excellent and similar to or better than the CSS . The mean score change was linearly related to the patient 's global self- assessment , although the CSS symptom and total score better discriminated patients with major or moderate degrees of improvement . CONCLUSIONS This study demonstrates the validity and responsiveness of a new rhinosinusitis-specific HRQL instrument , the Rhinosinusitis Quality of Life survey , in patients with chronic sinusitis . The instrument 's symptom frequency , bothersomeness , and impact scales compare favorably with a previously vali date d disease-specific and a generic HRQL measure . If vali date d in other patient population s , this disease-specific instrument may be useful in assessing severity and outcomes of treatment for sinusitis OBJECTIVES We assessed the effects of endoscopic sinus surgery on quality of life of patients with nasal polyposis or chronic sinusitis . PATIENTS AND METHODS Thirty patients ( 5 females , 25 males ; mean age 36 years ; range 17 to 58 years ) who underwent endoscopic sinus surgery were prospect ively evaluated . The diagnoses were nasal polyposis in 15 patients and chronic sinusitis in 15 patients . Primary and revision operations were performed in 23 patients and seven patients , respectively . The quality of life was evaluated before and six months after surgery with the use of the Chronic Sinusitis Survey ( CSS ) , and Medical Outcomes Study Short Form-12 ( SF-12 ) . Prior to administration , the two question naires were translated and adapted to Turkish . Computed tomography ( CT ) findings were scored before and six months after surgery according to the Lund-Mackay system . The results of the surveys were compared with CT scores . RESULTS The postoperative SF-12 and CSS scores of all the patients improved significantly . Computed tomography scores were not found in correlation with improvements in the SF-12 and CSS scores . CONCLUSION Endoscopic sinus surgery results in significant improvement in the quality of life of patients with nasal polyposis and chronic sinusitis , which may not be reflected by CT scores BACKGROUND : Psychiatric disorders are associated with increased symptom burden when combined with chronic medical conditions . However , there are no reports of how psychiatric distress influences outcomes with surgical treatment for chronic rhinosinusitis ( CRS ) . We hypothesized that subjects with psychiatric distress ( somatization , anxiety , and depression ) would report more severe long-term sinus symptoms and worse quality of life ( QOL ) than subjects without psychiatric distress . METHODS : This is a community-based , prospect i ve , observational cohort study of patients diagnosed with CRS presenting for surgery . Patients were interviewed before surgery ; CT scans were review ed , and question naires were completed about sinusitis-related symptoms ( SNOT-16 ) , general health status and QOL ( SF-36 ) , and psychiatric distress ( BSI and PHQ ) . Outcomes were also assessed 1 , 3 , 6 , and 12 months postoperatively . RESULTS : Ninety-five patients had complete records for analysis . Psychiatric distress was prevalent , with 31 % screening positive for somatization , 17 % positive for anxiety , and 25 % positive for depressive disorders . Subjects with somatization had significantly worse SNOT-16 scores at each time point compared with those without somatization ( P < 0.05 ) . Subjects with depression reported more severe symptoms at 6 and 12 months after surgery than those without depression ( P < 0.05 ) . The presence of somatization preoperatively was also independently associated with worse symptom severity 12-months after surgery , even after adjusting for prior sinus surgery , CT stage , Charlson Index , and deviated septum . In addition , subjects with psychiatric distress reported significantly worse SF-36 physical and mental component summary scores 12-months after surgery than subjects without psychiatric distress . CONCLUSIONS : Psychiatric distress is associated with worse reported sinus symptoms and lower QOL throughout surgical management of chronic rhinosinusitis . Despite this , subjects with psychiatric distress report a similar degree of improvement in sinus symptoms after surgery compared with those without distress . CLINICAL SIGNIFICANCE : Psychiatric distress should be considered in patients with persistent symptoms after surgery . Psychiatric distress should also be considered in efforts to design a chronic sinusitis staging system The Medical Outcome Study Short-Form 36-item Health Survey ( SF-36 ) was used to prospect ively assess outcomes after endoscopic sinus surgery . Our study found that chronic rhinosinusitis has a significant adverse impact on patient-perceived functional status and quality of life . Endoscopic sinus surgery result ed in statistically significant improvement in both disease-specific symptoms and patient-perceived global health status at 6 and 12 months of follow-up . The SF-36 is recommended for use as the global health monitor in outcomes evaluation for chronic rhinosinusitis OBJECTIVES : Studies examining the early postoperative period after endoscopic sinus surgery ( ESS ) are lacking . The objectives were to determine patient expectations of recovery following ESS and compare these expectations to actual outcomes . STUDY DESIGN : A prospect i ve study . An 11-item survey regarding recovery from anesthesia and sinonasal outcomes was administered after ESS over postoperative days ( POD ) # 1 , # 7 , and # 14 . Preoperative surveys established baseline levels and explored patient expectations of POD # 1 outcomes . RESULTS : Forty-six patients participated . Individual expectations generally did not correlate with POD # 1 outcomes . Sinonasal symptoms , narcotic usage , and activity level ( P < 0.05 ) demonstrated significant improvement over the postoperative period . Within one week , 75 % of patients returned to work . By POD # 14 , nasal obstruction , discharge , fatigue , and overall health ( P < 0.05 ) had improved over preoperative levels . Patients undergoing concomitant septoplasty had a more difficult postoperative course . CONCLUSION : Patient expectations of ESS vary widely , although this surgery is generally well tolerated with a brief recovery period . EBM rating : C-4 © 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation , Inc. All rights reserved OBJECTIVE : To test whether subscales should be used when analyzing the Sino-Nasal Outcome Test ( SNOT ) . STUDY DESIGN AND SETTING : Prospect i ve cohort study involved 87 acute NHS hospitals in Engl and and Wales . RESULTS : With the use of exploratory factor analysis we found evidence for the existence of four unique constructs within the SNOT . Two constructs address symptoms ( rhinologic and ear/facial ) and two address aspects of health-related quality of life ( psychological issues and sleep function ) . Subscales of the SNOT that correspond to these constructs provided clinical ly meaningful information over and above that provided by the SNOT total score on the type of surgical benefits gained by patients with different sino-nasal conditions . CONCLUSION : The SNOT is not unidimensional and a SNOT total score will mask variation in the true underlying constructs . SIGNIFICANCE : The SNOT would have greatly improved clinical use if it was scored with appropriate subscales . Such a measure would allow us to tease out the differential impact of sino-nasal conditions , in addition to allowing greater underst and ing of treatment effects Background The aim of this study was to determine the influence of asthma on sinus computed tomography ( CT ) grade , endoscopic appearance , and symptom scores in patients undergoing revision functional endoscopic sinus surgery ( FESS ) . Methods Prospect i ve data was collected of patients undergoing revision FESS at a tertiary medical center over a 2-year period . CT scans were grade d as per the Lund and Mackay system . Patient symptom scores were recorded from the Sino-Nasal Outcome Test ( SNOT 20 ) inventory and individual symptoms from the Rhinosinusitis Task Force major and minor symptom list were grade d on a visual analog scale . Results Eighty patients underwent revision FESS and 20 of those patients had asthma . The average CT grade in asthmatic patients was 18.6 compared with 11.7 in patients who were nonasthmatic ( p = 0.000006 ) . The average SNOT 20 symptom score in patients with asthma was 49.6 and in nonasthmatic patients it was 44.9 ( p = 0.238 ) . Both asthmatic and nonasthmatic patients experienced a reduction in SNOT 20 symptom scores at 1 year with reductions of 70 % ( p = 0.0000)versus 72.6 % ( p = 0.0000 ) , respectively . Conclusion Patients with asthma undergoing revision FESS had higher sinus CT grade s compared with patients without asthma . Asthmatic and nonasthmatic patients had statistically significant reductions in symptoms scores after revision FESS . Asthmatic patients had similar symptomatic relief scores after revision FESS as compared with nonasthmatic patients OBJECTIVE To determine if patients undergoing revision endoscopic sinus surgery ( ESS ) for chronic rhinosinusitis obtain significant symptomatic benefit from surgery . DESIGN Prospect i ve controlled clinical trial . METHODS Adult patients undergoing revision ESS were evaluated preoperatively with a computed tomographic scan and the Rhinosinusitis Symptom Inventory . After the revision ESS , patients were reevaluated with the Rhinosinusitis Symptom Inventory . Data were analyzed for symptom score changes and effect sizes , changes in medication , and economic variables . Improvements in sinonasal symptom scores , medication use , and economic variables were compared with those of a contemporaneous control group of patients undergoing primary ESS and matched for age , sex , and Lund score . RESULTS The 21 patients ( mean age , 44.8 years ) who completed evaluation after revision ESS had a mean follow-up of 12.4 months . Mean preoperative Lund score was 12.6 . Large effect sizes indicating significant symptom improvements were noted for nasal obstruction ( effect size , -1.9 ) , hyposmia ( -0.9 ) , and headache ( -0.6 ) , as well as nasal ( -1.1 ) and total symptom domains ( -0.9 ; P<.05 in all cases ) . Nasal steroid and nonsedating antihistamine use did not decrease significantly after ESS , but oral antibiotic use showed a downward trend ( net change , - 2.9 wk/y ; P = .23 ) . Improvements in clinical symptoms were statistically similar to corresponding improvements in the matched cohort of patients undergoing primary ESS . CONCLUSIONS The symptomatic relief that revision ESS can provide for patients with refractory chronic rhinosinusitis is similar to that following a primary ESS . However , many patients undergoing revision ESS require continued intense medical management of their chronic rhinosinusitis OBJECTIVES : Although endoscopy has been shown by a few authors to be a valuable tool for the diagnosis of chronic rhinosinusitis , its true role in the evaluation of the patient with chronic rhinosinusitis has not been eluci date d. The current definition of chronic rhinosinusitis is a symptom-based definition , and objective testing such as endoscopy or computed tomography ( CT ) is not included . However , the current treatment paradigm for chronic rhinosinusitis is dependent on the definition for diagnosis . Patients are treated with 4 weeks of antibiotics and decongestant/antihistamines/steroids based on the definition . This study aims to evaluate in a prospect i ve fashion the place of endoscopy in the diagnosis of chronic rhinosinusitis . STUDY DESIGN : A group of 78 patients meeting the definition of chronic rhinosinusitis were subjected to same-day endoscopy and CT scanning . RESULTS : Seventeen ( 22 % ) of 78 patients had positive endoscopic and CT results . There were 20 ( 26 % ) of 78 patients with negative endoscopic and positive CT results . Six ( 8 % ) patients had positive endoscopic and negative CT results , and 35 ( 45 % ) had negative endoscopic and negative CT results . Overall , 37 ( 47 % ) patients had positive CT results , and 41 ( 53 % ) patients had negative CT results . Endoscopy showing the presence of purulence , nasal polyps , or watery congested mucosa correlated well with CT results . Negative endoscopy correlated with CT results in 65 % of patients . CONCLUSION : The use of endoscopy to corroborate the diagnosis in nonpolypoid or nonpurulent rhinosinusitis in previously unoperated patients is question ed . Patients who meet the subjective definition of chronic rhinosinusitis should have a high degree of sensitivity and specificity with endoscopy or CT . The fact this is not the case questions the accuracy of the definition and the treatment paradigm . SIGNIFICANCE : According to this study , positive endoscopic results correlated well with CT , and negative endoscopic results correlated in 71 % of patients with negative CT results OBJECTIVES To conduct the first prospect i ve , r and omized , controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis ( CRS ) . MATERIAL S AND METHODS Ninety patients with CRS were equally r and omized either to medical or surgical therapy . All patients underwent pre- and posttreatment assessment s of visual analogue score ( VAS ) , the Sinonasal Outcome Test-20 ( SNOT-20 ) , the Short Form 36 Health Survey ( SF-36 ) , nitric oxide ( NO ) , acoustic rhinometry , saccharine clearance time ( SCT ) , and nasal endoscopy . Each patient had three assessment s : before starting the treatment , after 6 months , and , finally , after 1 year . RESULTS Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS ( P < .01 ) , with no significant difference being found between the medical and surgical groups ( P > .05 ) , except for the total nasal volume in CRS ( P < .01 ) and CRS without polyposis ( P < .01 ) groups , in which the surgical treatment demonstrated greater changes . CONCLUSION CRS should be initially targeted with maximal medical therapy ( e.g. , a 3 month course of a macrolide antibiotic , douche , and topical steroid ) , with surgical treatment being reserved for cases refractory to medical therapy . The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy , either surgical or medical Background The aim of this study was to compare Rhinosinusitis Task Force ( RSTF ) symptom scores with Sinonasal Outcome Test 20 ( SNOT-20 ) in patients with chronic rhinosinusitis ( CRS ) and controls . Methods An analysis was performed of prospect ively collected data in patients with CRS ( n = 201 ) and controls ( n = 100 ) . The severity of individual RSTF major and minor symptom scores grade d on a visual analog scale and total symptom scores were compared between the two groups . Correlation of the RSTF symptoms with the SNOT-20 was performed using data collected from the CRS group at baseline and at 1 year postoperatively . Results CRS patients had higher RSTF symptom scores compared with control patients when asked to rate the severity of nasal obstruction , facial pain/pressure , facial congestion , alteration of smell , nasal discharge , postnasal drip , headache , halitosis , fatigue , cough , and ear pain ( p < 0.005 ) . No statistically significant difference was seen for the symptoms of dental pain and fever . Total RSTF scores were 54.5 ± 1.9 in CRS patients versus 23.4 ± 3.0 in controls . Total SNOT-20 scores were 28.7 ± 0.8 in CRS patients versus 15.2 ± 0.6 in controls . In CRS patients , total RSTF scores correlated with total SNOT-20 scores at baseline ( r = 0.36 ; p < 0.0001 ) and 1-year postoperatively ( r = 0.37 ; p < 0.0001 ) . Conclusion Total RSTF symptom scores are significantly different in patients with chronic rhinosinusitis compared with those without this disease . The total RSTF symptom scores also correlate with a vali date d outcome measures instrument Background As the population ages , the mean age of patients with chronic rhinosinusitis ( CRS ) likely will increase as will the frequency of endoscopic sinus surgery ( ESS ) in the older population . The purpose of this study was to compare symptom presentation , CT scores , endoscopy scores , and quality of life ( QOL ) measures in patients < 60 years of age as compared with younger patients . Methods A prospect i ve cohort of 18 patients > 60 years and 121 patients ≤60 years undergoing ESS for CRS were studied . Patient factors , symptom severity , and CT scores were examined preoperatively . Endoscopy and QOL scores were compared pre- and postoperatively between the two groups . Results The prevalence of allergies , polyps , asthma , aspirin sensitivity , and revision surgery was similar in each age group . There was no statistically significant difference in the visual analog scale scores of symptom severity in each age group . Older patients had scores that were similar to younger patients with regard to CT ( 13.11 versus 11.63 ; p = 0.419 ) , preoperative endoscopy ( 8.22 versus 7.96 ; p = 0.828 ) , postoperative endoscopy ( 3.06 versus 4.82 ; p = 0.100 ) , and change in endoscopy ( −5.17 versus −3.15 ; p = 0.083 ) . Older patients had similar preoperative , postoperative , and change scores when compared with younger patients on the Rhinosinusitis Disability Index ( −15.33 versus −20.63 ; p = 0.318 ) and Chronic Sinusitis Survey ( 14.35 versus 23.11 ; p = 0.126 ) . Conclusion Older patients with CRS present with symptoms and patient factors that are comparable with younger patients and have a similar degree of improvement on endoscopy scores and QOL measures after ESS Background : Nasal polyposis ( NP ) is not a life‐threatening disorder but may have a great impact on the quality of life ( QoL ) . The objective of this study : ( i ) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form‐36 Health Survey ( SF‐36 ) question naire ; ( ii ) to compare the QoL outcome after medical or surgical treatment ; and ( iii ) to assess and compare the effect of medical and surgical treatment on nasal symptoms |
566 | 21,296,859 | A recent systematic review and meta analysis from the Canadian Critical Care Trials Group concluded that critically ill patients receiving HES were more likely to receive renal replacement therapy , and identified a trend toward increased risk of death in association with HES for patients with severe sepsis . | The choice of fluids for intravascular volume replacement has been debated for decades .
As early as 1919 , Benjamin Moore eloquently commented on the relative merits of colloids and crystalloids in different types of shock .
More recently , this debate has focused not only on colloids versus crystalloids , but more specifically on the choice of colloid solutions .
Hydroxyethyl starch ( HES ) solutions were developed as less-expensive alternatives to albumin .
HES solutions vary in their median molecular weight , molecular weight distribution , ratio between C2:C6 hydroxyethylation , and the type of diluent used .
The goal to reduce side effects was an important motivation for the different compositions , but clinical evidence for their improved safety is inadequate .
Today , the safety of HES solutions is still debated , with the additional complicating factor of commercial interests attempting to influence the argument . | UNLABELLED The effects of intravascular volume replacement regimens on tissue oxygen tension ( ptiO(2 ) ) are not definitely known . Forty-two consecutive patients scheduled for elective major abdominal surgery were prospect ively r and omized to receive either 6 % hydroxyethyl starch ( HES ) ( mean molecular weight 130 kd , degree of substitution 0.4 , n = 21 ) or lactated Ringer 's solution ( RL , n = 21 ) for intravascular volume replacement . Fluids were administered perioperatively and continued for 24 h on the intensive care unit to keep central venous pressure between 8 and 12 mm Hg . The ptiO(2 ) was measured continuously in the left deltoid muscle by using microsensoric implantable partial pressure of oxygen catheters after the induction of anesthesia ( baseline , T0 ) , 60 min ( T1 ) and 120 min thereafter ( T2 ) , at the end of surgery ( T3 ) , and on the morning of the first postoperative day on the intensive care unit ( T4 ) . HES 130/0.4 2920 + /- 360 mL and 11,740 + /- 2,630 mL of RL were given to the patients within the study period . Systemic hemodynamics and oxygenation ( PaO(2 ) , PaCO(2 ) ) did not differ significantly between the two volume groups throughout the study . From similar baseline values , ptiO(2 ) increased significantly in the HES-treated patients ( a maximum of 59 % at T4 ) , whereas it decreased in the RL group ( a maximum of -23 % at T4 , P < 0.05 ) . The largest differences of ptiO(2 ) were measured on the morning of the first postoperative day . We conclude that intravascular volume replacement with 6 % HES 130/0.4 improved tissue oxygenation during and after major surgical procedures compared with a crystalloid-based volume replacement strategy . Improved microperfusion and less endothelial swelling may be responsible for the increase in ptiO(2 ) in the HES 130/0.4-treated patients . IMPLICATION S In patients undergoing major abdominal surgery , a colloid-based ( with hydroxyethyl starch [ HES ] 130/0.4 ) and a crystalloid-based ( with lactated Ringer 's solution [ RL ] ) volume replacement regimen was compared regarding tissue oxygen tension ( ptiO(2 ) ) measured continuously by microsensoric implantable catheters . The ptiO(2 ) increased in the HES-treated ( + 59 % ) but decreased in the RL-treated ( -23 % ) patients . Improved microcirculation may be the mechanism for the better ptiO(2 ) in the HES group Objective Both albumin and synthetic colloids such as hydroxyethyl starch ( HES ) solution are used to optimize hemodynamics in the critically ill . The influence of different long-term infusion regimes on platelet function was studied . Design Prospect i ve , r and omized study . Setting Clinical investigation on a university hospital surgical intensive care unit . Patients Twenty-eight consecutive trauma patients ( injury severity score>15 points ) and 28 consecutive nontraumatized surgical patients with sepsis . Interventions The patients received either 20 % human albumin ( HA trauma , n=14 ; HA sepsis , n=14 ) or 10 % low-molecular-weight HES solution HES 200/0.5 ( HES trauma , n=14 ; HES sepsis;n=14 ) for 5 days to maintain central venous pressure and /or pulmonary capillary wedge pressure between 12 and 16 mmHg . Measurements and results Platelet function was assessed by aggregometry ( = turbidimetric technique ) using adenosine diphosphate 2.0 μmol/l , collagen 4 μl/ml , and epinephrine 25 μmol/l as inductors . Arterial blood was sample d on the day of admission or the day of diagnosis of sepsis ( = baseline value ) and over the next 5 days . St and ard coagulation parameters ( antithrombin III , fibrinogen , partial thromboplastin time ) were also measured . Total use of HES by the 5th day totalled 4870±990 ml in the trauma and 3260±790 ml in the sepsis patients ( HA trauma : 1850±380 ml ; HA sepsis : 1790±400 ml ) . Maximum platelet aggregation decreased significantly during the first 2–3 days after baseline in all groups . At the end of the investigation period , platelet aggregation variables had recovered and reached ( or even exceeded ) baseline values . Within the entire investigation period , the course of platelet aggregation variables did not differ significantly between HA and HES-treated patients irrespective of whether they were trauma or sepsis patients . Conclusions Alterations in hemostasis may occur for several reasons in the critically ill . Human albumin is the preferred first-line volume therapy in patients at risk for coagulation disorders . With respect to platelet function , volume replacement with ( lower-priced ) low-molecular-weight HES solutions can be recommended in this situation without any risk BACKGROUND It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units ( ICUs ) affects survival . We conducted a multicenter , r and omized , double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU . METHODS We r and omly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days . The primary outcome measure was death from any cause during the 28-day period after r and omization . RESULTS Of the 6997 patients who underwent r and omization , 3497 were assigned to receive albumin and 3500 to receive saline ; the two groups had similar baseline characteristics . There were 726 deaths in the albumin group , as compared with 729 deaths in the saline group ( relative risk of death , 0.99 ; 95 percent confidence interval , 0.91 to 1.09 ; P=0.87 ) . The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups ( P=0.85 ) . There were no significant differences between the groups in the mean ( + /-SD ) numbers of days spent in the ICU ( 6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group , P=0.44 ) , days spent in the hospital ( 15.3+/-9.6 and 15.6+/-9.6 , respectively ; P=0.30 ) , days of mechanical ventilation ( 4.5+/-6.1 and 4.3+/-5.7 , respectively ; P=0.74 ) , or days of renal-replacement therapy ( 0.5+/-2.3 and 0.4+/-2.0 , respectively ; P=0.41 ) . CONCLUSIONS In patients in the ICU , use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days BACKGROUND The role of intensive insulin therapy in patients with severe sepsis is uncertain . Fluid resuscitation improves survival among patients with septic shock , but evidence is lacking to support the choice of either crystalloids or colloids . METHODS In a multicenter , two-by-two factorial trial , we r and omly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10 % pentastarch , a low-molecular-weight hydroxyethyl starch ( HES 200/0.5 ) , or modified Ringer 's lactate for fluid resuscitation . The rate of death at 28 days and the mean score for organ failure were co primary end points . RESULTS The trial was stopped early for safety reasons . Among 537 patients who could be evaluated , the mean morning blood glucose level was lower in the intensive-therapy group ( 112 mg per deciliter [ 6.2 mmol per liter ] ) than in the conventional-therapy group ( 151 mg per deciliter [ 8.4 mmol per liter ] , P<0.001 ) . However , at 28 days , there was no significant difference between the two groups in the rate of death or the mean score for organ failure . The rate of severe hypoglycemia ( glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was higher in the intensive-therapy group than in the conventional-therapy group ( 17.0 % vs. 4.1 % , P<0.001 ) , as was the rate of serious adverse events ( 10.9 % vs. 5.2 % , P=0.01 ) . HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer 's lactate . CONCLUSIONS The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia . As used in this study , HES was harmful , and its toxicity increased with accumulating doses . ( Clinical Trials.gov number , NCT00135473 . Objective There is continuing concern on the influence of hydroxethyl starch ( HES ) on renal function . Design Prospect i ve , r and omized study . Setting University-affiliated medical center . Patients Forty consecutive patients aged > 70 years undergoing cardiac surgery using cardiopulmonary bypass . Interventions Either low-molecular HES ( mean molecular weight : 130 kD ) with low degree of substitution ( 0.4 ) ( 6 % HES 130/0.4 ) ( n=20 ) or gelatin ( n=20 ) was given after induction of anesthesia until the 2nd postoperative day ( POD ) to keep central venous pressure between 12–14 mmHg . Measurements and results Creatinine clearance ( CC ) and fractional sodium clearance ( FSC ) were measured . N-acetyl-beta-D-glucosamidase , alpha-1-microglobulin , glutathione transferase-pi , and glutathione transferase-alpha were measured from urine specimens . Measurements were made after induction of anesthesia , at the end of surgery , and at the first and the second POD . More gelatin ( total : 4150±490 ml ) than HES 130/0.4 ( total : 3450±450 ml ) was infused within the study . CC and FSC were without differences between the two groups . All measured kidney-specific proteins were almost within normal range at baseline . They increased significantly after surgery , however , without significant group differences . At the 2nd POD , kidney-specific proteins had returned almost to normal values . None of the patients developed acute renal failure . Conclusions Sensitive markers of kidney dysfunction increased in our elderly patients indicating moderate alterations in kidney integrity during cardiac surgery . The two volume replacement regimens did not differ with regard to kidney integrity in elderly patients undergoing cardiac surgery Various vasoactive substances are involved in the regulation of the macro- and microcirculation . We have investigated if these regulators change during long-term volume therapy with human albumin ( HA ) or hydroxyethylstarch solution ( HES ) in trauma and sepsis patients . To maintain pulmonary capillary wedge pressure ( PCWP ) at 10 - 15 mm Hg , either 20 % HA ( HA-trauma , n = 14 ; HA-sepsis , n = 14 ) or 10 % low-molecular weight HES solution ( HES-trauma , n = 14 ; HES-sepsis , n = 14 ) were infused for 5 days , otherwise patient management did not differ between the two groups ( trauma/sepsis ) . Mean arterial pressure ( MAP ) , heart rate ( HR ) , PCWP and cardiac index ( CI ) were monitored in all patients . Liver function was assessed using the monoethylglycinexylidide ( MEGX ) test , and gastric intramucosal pH ( pHi ) was monitored by tonometry to assess splanchnic perfusion . Plasma concentrations of vasopressin , endothelin-1 , adrenaline , noradrenaline , atrial natriuretic peptide and 6-keto-prostagl and in F1 alpha were measured from arterial blood sample s. All measurements were carried out on the day of admission to the intensive care unit ( trauma patients ) or on diagnosis of sepsis , and daily over the next 5 days at 12:00 . MAP , HR and PCWP did not differ between the corresponding subgroups ( trauma/sepsis ) . Cl increased significantly more in the HES than in the HA groups . pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study . Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients ( P < 0.05 ) . In the trauma patients , concentrations of all vasoactive regulators were very similar in both groups . In both sepsis groups , vasopressors ( vasopressin , endothelin-1 , noradrenaline and adrenaline ) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients . Concentrations of atrial natriuretic peptide increased only in the HA patients ( from 159 ( SD 31 ) to 215 ( 38 ) pg ml-1 on day 2 ) . Plasma concentrations of 6-keto-prostagl and in F1 alpha decreased significantly only in the HES sepsis patients ( from 112 ( 25 ) to 47 ( 15 ) pg ml-1 ) Not enough fluid and too much fluid are both bad . That is the one great irrefutable truth in fluid management in anaesthesia and in the critically ill . For almost every other question in fluid therapy there is ‘ current opinion ’ . The big questions are when , where , which and why but of greater moment than all of these is ‘ how much ’ . The current drift towards the use of smaller volumes of fluid in major surgery suggests that the right amount at the right time is probably the way to go , so volume and timing are seemingly linked . This ties in neatly with the rediscovery of the notion that early fluid resuscitation in the emergency room is better than late and dovetails with the concept that adequate resuscitation , or optimisation , improves outcome in high risk surgery . New gadgets that help to achieve this end abound since the pulmonary artery catheter fell from grace . The recent discovery of hyperchloraemic acidosis as a new iatrogenic disease entity has focused attention on the importance of the fundamental constituents of the fluids that are given [ 1 ] . The meta-analytical cloud that the Cochrane collaboration placed over albumin was dissipated by the SAFE study only to be replaced by a different evidential cloud drifting over the world of starches [ 2 ] . This has reawakened interest in the potentially malevolent nature of synthetic molecules . As the dynamics of the questions and current answers change , it is easy to become confused . The publication of the British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients could therefore not be more timely [ 3 ] . The authors have asked a very large number of relevant questions , assessed a vast array of available information and measured it with an evidence -based score to produce recommendations bundled into guidelines . There are no less than 28 evidence -scored recommendations to assist in fluid management . This major work should be m and atory reading for anyone involved in fluid management for a range of reasons that will come clear . The recommendations , all 28 of them , each has an evidence level of between 1 and 5 , although some have several evidence levels for different parts of the same question . In brief ; level 1 is very good , 1a – a systematic review or 1b a r and omised control trial , while level 4 is a case series and level 5 is expert opinion without critical appraisal , so ‘ 1 – good and 5 – bad ’ . The first recommendation dismisses normal saline from routine use because it causes hyperchloraemic acidosis , and advocates balanced solutions . The evidence level is 1b and appears to be very good using no fewer than seven papers . On closer scrutiny some of these are small r and omised controlled trials which demonstrate mild acidosis [ 4–9 ] . Saline and hyperchloraemic acidosis are associated and by implication this is harmful , although any evidence for harm is circumstantial and inconsequential [ 10 ] . The recommendation , supportive of balanced solutions , is inappropriate given the limited evidence ( this author ’s opinion – level 5 ) . Sensible maybe , but evidence -based ? To be fair , many of the recommendations have been st and ard practice for years and , paradoxically , several of these are level 5 . The pre-operative recommendations may raise eyebrows . Most anaesthetists know that fluids can be given orally up to 2 h pre-operatively but how many actively encourage it despite the evidence level of 1a ? The implication is there should be a general and active move to 2-h fluid fasting . These guidelines are based on three references , two of which are themselves guidelines and one being a Cochrane review . The fact that fluids make patients feel better is supported by trials and rates an evidence level of 2a . Curiously , the guidelines contain useful tips on the current position of bowel preparation , grade d level 1a , while the predicted fluid and electrolyte disturbance which it causes only achieves level 5 . Mind you , using a parachute when jumping out of an aircraft presumably only gets a score of 4 [ 11 ] . It is curious that the Geigy Scientific tables for the electrolyte content of secretions rates level 5 while the Hartmann ’s vs saline question in the replacement of gastric losses rates level 2a , again largely because saline is associated with hyperchloraemic acidosis . No-one would argue that balanced crystalloid or a colloid can be used for the treatment of hypovolaemia but , of the 11 references quoted , nine involve starches , a curious selection from a very extensive literature , while balanced crystalloid is once again recommended because of the supposed risks of hyperchloraemic acidosis , if such risks exist . The recommendations move on to the diagnosis of hypovolaemia and the use of incremental 200-ml boluses of either crystalloid or colloid . This is level 1b evidence based on two small trials [ 12 , 13 ] . While one must question whether this constitutes substantial evidence , it does make sense . Orthopaedic and abdominal surgery are singled out to recommend stroke volume measurement to guide fluid management peri-operatively ( level 1b ) . In orthopaedic surgery this is based on two well known studies , each of which can be interpreted either to indicate that the intervention reduced hospital stay or that the control group could have been better managed . The former is more widely accepted . In non-elective surgery , in the same specialities , this management should continue for 8 h and , in these circumstances , low dose dopexamine , which performed well in a meta- analysis , is Anaesthesia , 2009 , 64 , pages 235–238 BACKGROUND Because patients with low albumin levels may benefit from human albumin ( HA ) administration , we studied correction of hypovolemia with HA in hypoalbuminic elderly cardiac surgery patients . METHODS In a prospect i ve , r and omized study , 50 patients aged > 80 yr undergoing cardiac surgery using cardiopulmonary bypass with a preoperative serum albumin concentration of < 3.5 mg/dL , received either 5 % HA ( n = 25 ) or hydroxyethyl starch ( 6 % HES 130/0.4 ) ( n = 25 ) . Volume was added to the priming ( 500 mL ) and given until the morning of the second postoperative day to keep pulmonary capillary wedge pressure or central venous pressure between 12 and 14 mm Hg . RESULTS Inflammatory response ( interleukins-6 , -10 ) , endothelial activation ( intercellular adhesion molecule-1 ) , and kidney function ( including glutathione transferase-alpha and neutrophil gelatinase-associated lipocalin ) were measured after induction of anesthesia , 5 h after surgery , and the first and second postoperative day . A follow-up , approximately 60 days after discharge from the hospital , was done . Two thous and nine hundred eighty + /- 430 mL of HA and 3060 + /- 680 mL of HES 130/0.4 were given . Serum albumin concentration was significantly increased by HA ( to 4.5 + /- 0.3 mg/dL ) . Serum creatinine , glomerular filtration rate , and urinary levels of alpha-glutathione transferase and neutrophil gelatinase-associated lipocalin were not different in the HA-compared to the HES-treated patients . The inflammatory response was similar in both groups , whereas endothelial activation was less in the HES group . None of the patients developed renal failure requiring renal replacement therapy . CONCLUSION Use of HA in hypoalbuminemic cardiac surgery patients aged > 80 yr was without benefit with regard to inflammatory response , endothelial activation , and renal function compared to 6 % HES 130/0.4 UNLABELLED Elderly patients are at risk of developing renal dysfunction . Synthetic colloids are often used perioperatively , but they may have detrimental effects on renal function . In a prospect i ve , r and omized study , we assessed the influence of different intravascular volume replacement regimens on renal function in elderly ( > 65 yr ) and younger ( < 65 yr ) patients without preoperative renal dysfunction who were undergoing major abdominal surgery . Either 6 % low molecular weight hydroxyethyl starch ( HES ) solution ( mean molecular weight 70,000 D , degree of substitution 0.5 ; HES 70/0.5 ) [ each group n = 10 ] ) , 6 % medium-molecular weight HES ( molecular weight 200,000 D , degree of substitution 0.5 ( HES 200/0.5 ) [ each group n = 10 ] ) , or modified gelatin ( molecular weight 35,000 D [ each group n = 10 ] ) was administered to maintain mean arterial blood pressure > 65 mm Hg and central venous pressure between 10 and 14 mm Hg . After the induction of anesthesia ( T0 ) ; at the end of surgery ( T1 ) ; 4 h after surgery ( T2 ) ; and on the first ( T3 ) , second ( T4 ) , and third postoperative days ( T5 ) , alpha1-microglobulin ( alpha1-M ) , N-acetyl-beta-glucosaminidase , fractional sodium clearance , and creatinine clearance ( CC ) were measured . Colloids ( 1300 - 3000 mL ) were infused until the first postoperative day . At T0 , urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups ( P < 0.05 ) . alpha1-M remained increased only in the gelatin group . N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups . At baseline , CC was significantly higher in the younger than in the elderly patients , but CC did not decrease in any of the intravascular volume replacement groups . We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction . IMPLICATION S We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery . Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics . As assessed by sensitive markers of renal function , all three regimens can be used safely for volume replacement without risking significant renal dysfunction OBJECTIVE To compare volume therapy with HES 130/0.4 , a new hydroxyethylstarch ( HES ) solution with a gelatin-based fluid replacement strategy . DESIGN Prospect i ve , r and omized , safety study . SETTING Urban , university-affiliated hospital ( single institution ) . PARTICIPANTS Forty-two patients undergoing elective cardiac surgery . INTERVENTIONS Patients were prospect ively r and omized into 2 groups : In group 1 ( n = 21 ) , gelatin was given perioperatively for volume support until the 1st postoperative day to keep the central venous pressure ( CVP ) between 10 and 14 mmHg ; in group 2 ( n = 21 ) HES 130/0.4 was administered using the same protocol as in group 1 . MEASUREMENTS AND MAIN RESULTS St and ard coagulation variables and modified thromboelastography ( TEG ) were used . Using different activators for extrinsic and intrinsic activation and heparin inactivation by heparinase , the onset of coagulation ( coagulation time ) , kinetics of clot formation ( clot formation time ) , and maximum clot firmness were measured . Measurements were performed after induction of anesthesia ( T0 ) , at the end of surgery ( T1 ) , 4 hours after surgery ( T2 ) , and on the morning of the 1st postoperative day ( T3 ) . A total of 3310 + /- 810 mL of gelatin and 3070 + /- 570 mL of HES 130/0.4 were used in the 2 groups during the study period . The 2 groups did not differ with regard to postoperative bleeding or in use of packed red blood cells or fresh frozen plasma . St and ard coagulation variables were similar between the 2 groups . All TEG variables were within the normal range at baseline . Coagulation time and clot formation time data were significantly elevated after surgery and in the intensive care unit , without showing specific differences between the 2 volume replacement groups . Intrinsic TEG and heparinase TEG clot formation times remained significantly higher until the end of the study period . No differences were seen between HES-treated and gelatin-treated patients . CONCLUSIONS Volume replacement with the new HES preparation was as safe as gelatin-based volume replacement with regard to coagulation in cardiac surgical patients . HES 130/0.4 is an alternative plasma substitute to treat volume deficits OBJECTIVE To compare the hemodynamic efficacy of a new hydroxyethyl starch ( HES ) preparation ( 130/0.4 ) with an HES 200/0.5 solution . DESIGN Prospect i ve , r and omized , double-blind , phase II study . SETTING An urban , university-affiliated hospital . PARTICIPANTS Twenty patients undergoing elective first-time cardiac surgery . INTERVENTIONS After induction of anesthesia and before the start of surgery , a new HES 130/0.4 ( molecular weight , 130,000 d ; degree of substitution , 0.4 ) ( n = 10 ) or HES 200/0.5 ( molecular weight , 200,000 d ; degree of substitution , 0.5 ) ( n = 10 ) was infused ( 10 mL/kg ) within 30 minutes when pulmonary capillary wedge pressure was less than 10 mmHg . MEASUREMENTS AND MAIN RESULTS Extensive hemodynamic monitoring was performed 30 and 60 minutes after the end of infusion . Then surgery was started . St and ard laboratory parameters were measured before surgery and on the 1st postoperative day . A similar amount of HES was given in both groups ( HES 130 , 795+/-75 mL ; HES 200 , 820+/-90 mL ) . Filling pressures ( central venous pressure , pulmonary capillary wedge pressure ) and cardiac index increased similarly in both groups and remained significantly elevated 60 minutes after the end of infusion . All other hemodynamic parameters were similar between the two volume groups . Renal ( creatinine ) and hepatic function ( aspartate aminotransferase , alanine aminotransferase ) and hemostasis ( platelet count , activated partial thromboplastin time , blood loss ) were without group differences until the morning of the 1st postoperative day . CONCLUSIONS The new 6 % HES 130/0.4 was as effective as a 6 % HES 200/0.5 preparation in regard to hemodynamic efficacy . No negative side effects on organ function were seen . The 6 % HES 130/0.4 solution may become an alternative strategy for volume therapy in cardiac surgery BACKGROUND The effects of hydroxyethylstarch ( HES ) 130/0.4 6 % and gelatin 4 % on inflammation , endothelial integrity , and renal function after cardiac surgery were compared . METHODS Sixty patients aged > 80 yr undergoing cardiac surgery were r and omized to receive gelatin ( n=30 ) or HES 130/0.4 ( n=30 ) . The colloid was used in the priming of the cardiopulmonary bypass circuit ( 500 ml ) and for volume replacement until the second postoperative day ( POD ) . Serum creatinine , creatinine clearance , IL-6 , IL-10 , intercellular adhesion molecule-1 ( sICAM-1 ) , urinary glutathione transferase-alpha , and neutrophil gelatinase-associated lipocalin ( NGAL ) were measured perioperatively . Serum creatinine was also reported approximately 60 days after discharge . RESULTS The mean(sd ) volume of gelatin infused was 4180(440 ) ml , which was greater than the volume of HES infused 2910(330 ) ml ( P=0.002 ) . The mean(sd ) volume of serum creatinine on the first POD was 151(24 ) micromol litre(-1 ) in the gelatin group and 126(13 ) micromol litre(-1 ) in the HES group ( P=0.004 ) . Values for the second POD were 161(0.26 ) and 133(16 ) micromol litre(-1 ) , respectively ( P=0.004 ) . Creatinine clearance was lower in the gelatin group on the first POD [ 37(7 ) vs 46(8 ) ml min(-1 ) 1.73 m2 ( P=0.004 ) ] and the second POD [ 32(8 ) vs 45(10 ) ml min(-1 ) 1.73 m2 ( P=0.002 ) ] . Kidney function approximately 60 days after discharge did not differ between the groups . IL-6 , IL-10 , and sICAM-1 were significantly lower in the HES group than in the gelatin group on the first and second PODs . Urinary alpha-GST increased in both groups to a comparable extent . Urinary NGAL concentrations were higher in the gelatin than in the HES patients 5 h after surgery and on the first and second PODs . CONCLUSIONS In cardiac surgery patients aged > 80 years , volume therapy with HES 130/0.4 6 % was associated with less marked changes in kidney function and a less marked endothelial inflammatory response than gelatin 4 % OBJECTIVE Adequate restoration of intravascular volume remains an important maneuver in the management of the surgical patient . Influence of different volume replacement regimens on inflammation/endothelial activation in elderly surgical patients was assessed . DESIGN Prospect i ve , r and omized study . SETTING Surgical intensive care unit of a university-affiliated hospital . PATIENTS Sixty-six patients > 65 years undergoing major abdominal surgery . INTERVENTIONS Ringer 's lactate ( RL ; n=22 ) , normal saline solution ( NS ; n=22 ) or a low-molecular HES ( mean molecular weight 130 kD ) with a low degree of substitution ( 0.4 ; HES 130/0.4 ; n=22 ) were administered after induction of anesthesia until the 1st postoperative day ( POD ) to keep central venous pressure between 8 - 12 mmHg . MEASUREMENTS AND RESULTS C-reactive protein , interleukins ( IL-6 , IL-8 ) , adhesion molecules [ endothelial leukocyte adhesion molecule-1 ( ELAM-1 ) and intercellular adhesion molecule-1 ( ICAM-1 ) ] were measured prior to volume therapy at the end of surgery , 5 h after surgery and at the morning of the 1st POD . RL patients received 10,150+/-1,660 ml of RL , NS patients 10,220+/-1,770 ml of NS and the HES-treated group 2,850+/-300 ml of HES 130/0.4 and 2,810+/-350 ml of RL . Hemodynamics were similar in all groups . CRP , IL-6 and IL-8 plasma levels increased significantly higher in both crystalloid groups ( IL-6 in the NS group : increase to 407+/-33 pg/ml ; RL : increase to 377+/-35 pg/dl ) than in the HES-130 treated group ( IL-6 : increase to 197+/-20 pg/dl ) . Plasma levels of ELAM-1 and ICAM remained almost unchanged in the HES 130- , but significantly increased in the RL- and NS-treated patients . CONCLUSIONS In elderly patients , markers of inflammation and endothelial injury and activation were significantly higher after crystalloid- than after HES 130/0.4-based volume replacement regimens The value of human albumin ( HA ) for treating hypovolemia is controversial . Less expensive alternatives such as hydroxyethyl starch ( HES ) are sometimes refused because of unwanted side effects . We prospect ively r and omized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5 % HA ( n = 25 ) or a third generation HES preparation ( 6 % HES 130/0.4 ; n = 25 ) when mean arterial blood pressure was < 60 mm Hg and central venous pressure was < 10 mm Hg . Hemodynamics , inflammation ( interleukin-6 ) , endothelial activation-integrity ( adhesion molecules ) , coagulation ( thrombelastography ) , and renal function ( including kidney-specific proteins ) were monitored after the induction of anesthesia , after surgery , 5 h in the intensive care unit , and on the first postoperative day . HA patients received 3960 + /- 590 mL of HA and 5070 + /- 1030 mL of Ringer 's lactate solution , and HES patients received 3500 + /- 530 mL of HES and 4550 + /- 880 mL of Ringer 's lactate solution . Total protein remained normal only in the HA-treated patients . No significant differences ( P > 0.1 ) between the groups were seen with regard to hemodynamics , coagulation , and kidney function . Plasma levels of interleukin-6 and soluble adhesion molecules were significantly ( P < 0.05 ) higher in the HA- than in the HES-treated patients . We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation . Because of the decreased inflammatory response and endothelial activation-injury , HES 130/0.4 seems to be the more appropriate fluid strategy for these patients Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient . The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight ( LMW ) hydroxyethyl starch solution ( HES ) differs from that of human albumin ( HA ) . According to a r and omized sequence , 30 trauma patients ( injury severity score [ ISS ] between 15 and 30 ) and 30 sepsis patients ( secondary to major general surgery ) received either 10 % HES ( mean molecular weight 200,000 daltons ; HES trauma [ n = 15 ] , HES sepsis [ n = 15 ] ) or human albumin 20 % ( HA trauma [ n = 15 ] , HA sepsis [ n = 15 ] ) over 5 days to keep pulmonary capillary wedge pressure ( PCWP ) between 12 and 18 mm Hg . Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days . Gastric intramucosal pH ( pHi ) was measured by tonometry . Central venous pressure and PCWP were comparable within the subgroups ( trauma/sepsis ) throughout the entire study period . In the trauma patients , cardiac index ( CI ) , oxygen consumption index ( VO2 I ) , and oxygen delivery index ( DO ( 2 ) I ) , significantly increased only in the HES-treated patients . In the sepsis patients , CI , VO2 I , and DO2 I increased and remained higher than baseline only in the HES group ( P < 0.01 ) . Right ventricular ejection fraction ( RVEF ) was reduced ( < 40 % ) in the HA patients and increased only in the HES patients ( from 34 % + /- 4 % to 42 % + /- 3 % ; P < 0.05 ) . pHi remained normal ( > 7.35 ) in both trauma groups and in the HES-treated sepsis patients . In the HA sepsis group , pHi decreased ( < 7.20 ) within the study period ( 7.15 + /- 0.12 on Day 4 ) , indicating deteriorated splanchnic perfusion . We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES . In both groups , volume replacement with HES even result ed in improved systemic hemodynamics . Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy . ( Anesth Analg 1996;83:254 - 61 In 30 consecutive children undergoing cardiac surgery , two different types of fluid were given r and omly for volume replacement in the pre-bypass period . In group 1 ( n = 15 ) , low molecular weight hydroxyethyl starch solution ( LMW-HES ) ( 6 % HES ; mean molecular weight 200,000 Da , molar substitution 0.5 ) and in group 2 ( n = 15 ) 20 % albumin ( HA ) was infused from the induction of anaesthesia until the start of cardiopulmonary bypass ( CPB ) . In addition to haemodynamic values , various laboratory variables were measured before and after CPB until the morning of the 1st day after operation . The patients did not differ in diagnosis and conduct of CPB ( lowest rectal temperatures : group 1 29.0 ( SD 1.1 ) degrees C ; group 2 29.4 ( 1.0 ) degrees C ) . Haemodynamic data ( MAP , HR , CVP ) , anti-thrombin-III , fibrinogen , platelet count and coagulation variables were comparable between the groups until the 1st day after operation . Postoperative blood loss and the use of homologous blood or blood products were similar in all children . Albumin concentration increased after infusion of albumin ( 35 - 47 g litre-1 ) and was significantly greater until the end of the operation compared with the LMW-HES-treated children . Colloid osmotic pressure , however , was similar in the two groups and returned to baseline values on the 1st day after operation ( LMW-HES group 19.31 ( 1.2 ) mm Hg ; HA group 18.0 ( 1.3 ) mm Hg ) . Post-bypass urine output and creatinine values also did not differ between the groups . Anaphylactic reactions were not observed in any of the patients . It can be concluded that LMW-HES solution can be used effectively and safely for volume replacement in the pre-bypass period in small children undergoing cardiac surgery Background and objective : The kind of fluid for correcting hypovolaemia is still a focus of debate . In a prospect i ve , r and omized , controlled and double‐blind study in patients undergoing major abdominal surgery , a total balanced volume replacement strategy including a new balanced hydroxyethyl starch ( HES ) solution was compared with a conventional , non‐balanced fluid regimen . Methods : In Group A ( n = 15 ) , a new balanced 6 % HES 130/0.42 was given along with a balanced crystalloid solution ; in Group B ( n = 15 ) , an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid ( saline solution ) were administered . Volume was given when mean arterial pressure ( MAP ) was < 65 mmHg and central venous pressure ( CVP ) minus positive end‐expiratoric pressure ( PEEP ) level was < 10 mmHg . Haemodynamics , acid – base status , coagulation ( thrombelastography ( TEG ) ) and kidney function ( including kidney‐specific proteins , N‐acetyl‐beta‐d‐glucosaminidase ( beta‐NAG ) and alpha‐1‐microglobulin ) were measured after induction of anaesthesia , at the end of surgery , 5 and 24 h after surgery . Results : Group A received 3533 ± 1302 mL of HES and 5333 ± 1063 mL of crystalloids , in Group B , 3866 ± 1674 mL of HES and 5966 ± 1202 mL of crystalloids were given . Haemodynamics , laboratory data , TEG data and kidney function were without significant differences between the groups . Cl− concentration and base excess ( −5 ± 2.4 mmol L−1 vs. 0.4 ± 2.4 mmol L−1 ) were significantly higher in patients of Group B than of Group A. Conclusions : A complete balanced volume replacement strategy including a new balanced HES preparation result ed in significantly less derangement in acid – base status compared with a non‐balanced volume replacement regimen . The new HES preparation showed no negative effects on coagulation and kidney function Synthetic colloids have been reported to cause haemorrhagic complications . The effects of perioperative volume replacement with 4 % gelatin ( n = 20 ) , 6 % low-molecular weight ( LMW ) hydroxyethyl starch ( HES ) ( Mw : 70,000 dalton ; HES 70/0.5 ; n = 20 ) and 6 % medium-molecular weight ( MMW ) HES ( Mw : 200,000 dalton ; HES 200/0.5 ; n = 20 ) on haemostasis were assessed in patients undergoing major abdominal surgery . Volume was administered to keep central venous pressure ( CVP ) between 10 and 14 mm Hg . Conventional global coagulation tests , molecular markers of coagulation , and platelet function ( using a platelet function analyser ( PFA-100 ) with ADP as inductor ) were monitored prior to surgery ( T0 ) , at the end of surgery ( T1 ) , 4 h after the end of surgery ( T2 ) , and on the morning of the first postoperative day ( T3 ) . Significantly more gelatin ( 2900 ( SD 320 ) ml ) than HES 200 ( 2150 ( 312 ) ml ) was given during the study period . Bleeding and the use of allogeneic blood-blood products were similar in all groups . Markers of thrombin generation ( F1 + 2 ) , of thrombin neutralization ( TAT III complex ) , and of fibrin formation and its degradation ( D-dimer ) increased significantly during and after surgery without showing significant group differences . Factor VIII and von Willebr and factor ( vWF ) also increased in all groups beyond the normal range , showing the significantly highest increase in the gelatin-treated group ( VIII : from 173 ( 36 ) to 266 ( 33 ) U dl-1 ; vWF : from 164(33 ) to 238 ( 31 ) U dl-1 ) . Platelet function remained within the normal range and without group differences throughout the study period . We can conclude that all three solutions can be used safely in patients undergoing major abdominal surgery with regard to the haemostatic process UNLABELLED A new hydroxyethyl starch ( HES ) preparation with a mean molecular weight of 130,000 daltons and a degree of substitution of 0.4 shows favorable pharmacokinetic properties . We conducted a study of the influence of the new HES specification on coagulation and compared it with another colloidal intravascular volume replacement regimen using gelatin . According to a prospect i ve , r and om sequence , 42 patients undergoing major abdominal surgery received either HES 130/0.4 ( n = 21 ) or gelatin ( n = 21 ) until the first postoperative day ( POD ) to keep central venous pressure between 10 and 14 mm Hg . From arterial blood sample s , st and ard coagulation variables were measured , and modified thrombelastogram ( TEG ) measurements using different activators were performed . A total of 2830 + /- 350 mL of gelatin and 2430 + /- 310 mL of HES 130/0.4 were administered until the morning of the first POD . The use of allogeneic blood/blood products and st and ard coagulation variables did not differ significantly between the two groups . After induction of anesthesia , all TEG data for both groups were within normal range . Coagulation time and maximum clot firmness did not change significantly in any TEG measurements during the study period . The kinetics of clot formation ( clot formation time ) significantly increased immediately after surgery , but without showing significant group differences . On the morning of the first POD , the clot formation time returned to almost normal levels , except for aprotinin-activated TEG(R ) . We conclude that administration of moderate doses of the new HES 130/0.4 preparation in patients undergoing major abdominal surgery results in similar coagulation alterations as those after using an established gelatin-based volume-replacement regimen . IMPLICATION S We compared the effects of infusion of a new hydroxyethyl starch preparation ( 6 % hydroxyethyl starch ; mean molecular weight 130,000 daltons ; degree of substitution 0.4 ) on coagulation with a gelatin-based intravascular volume replacement regimen in patients undergoing major abdominal surgery . After moderate doses of hydroxyethyl starch ( 2430 + /- 310 mL until the morning of the first postoperative day ) , coagulation monitoring , including modified thrombelastography , did not show impaired hemostasis Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process . Besides neutrophil and endothelial‐bound adhesion molecules , soluble forms have been detected in the circulating blood . They seem to be good markers of endothelial damage , but they may also have other biological functions . Plasma concentrations of soluble adhesion molecules ( endothelial leucocyte adhesion molecules ( sELAM‐1 ) , intercellular adhesion molecule‐1 ( sICAM‐1 ) , vascular cell adhesion molecule‐1 ( sVCAM‐1 ) , and granule membrane protein 140 ( sGMP‐140 ) were serially measured over 5 days by enzyme‐linked immunosorbent assays ( ELISA ) in 45 consecutive trauma patients . These received , by r and om allocation , only either hydroxyethylstarch solution 10 % ( mean molecular weight 200 000 daltons ) ( n = 15 ) or human albumin 20 % ( n = 15 ) for volume therapy . Another 15 patients without defined volume therapy received pentoxifylline continuously ( 1.2mg.kg‐1.h‐1 ) . Measurements were carried out on the day of admission to the intensive care unit ( baseline ) and during the next 5 days . At baseline , plasma concentrations of all adhesion molecules were similar in all groups . In the hydroxyethyl starch group , sELAM‐1 and sICAM‐1 concentrations decreased significantly ( p < 0.05 ) reaching normal values during the study period whereas the mean ( SD ) values increased in the pentoxifylline group ( sELAM‐1 : 71.1 ( 16.7 ) to 91.6 ( 17.8 ) ng.ml‐1 ) and the albumin group ( sICAM‐1 : 400 ( 81 ) to 749 ( 101 ) ng.ml‐1 ) ( p < 0.05 ) . sVCAM‐1 increased outside the normal range only in the human albumin group ( to 760 ± 69 ng.ml‐1 ) ( p < 0.05 ) . sGMP‐140 plasma concentration increased only in those receiving albumin ( 432 ( 85 ) to 550 ( 93 ) ng.ml‐1 ) and this was significantly different to the other groups ( p < 0.05 ) . None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules . We conclude that colume therapy with hydroxyethyl starch result ed in a decrease in circulating adhesion molecules in our trauma patients . In contrast , volume therapy with albumin did not exert this effect . Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin ( TM ) . The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospect i ve , r and omized study . Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10 % low-molecular weight ( LMW ) hydroxyethylstarch solution ( HES-trauma , n = 15 ; HES-sepsis , n = 15 ) or 20 % human albumin ( HA-trauma , n = 15 ; HA-sepsis , n = 15 ) for 5 days to maintain central venous pressure ( CVP ) between 12 and 16 mm Hg . Plasma concentrations of TM , protein C , ( free ) protein S and thrombin-antithrombin ( TAT ) were measured in arterial blood sample s obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days . There were no differences between HA- and HES-treated trauma patients . Protein C and protein S also did not differ between HA- and HES-treatments . At baseline , TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only . In the HA-sepsis group , TM increased significantly ( from 48.1 ( SD 13.9 ) to 68.4 ( 13.0 ) micrograms litre-1 ) , whereas it remained almost unchanged in the HES-sepsis group . In HES-sepsis patients , protein C ( from 51.0 ( 10.1 ) to 71.9 (8.9)% ) and protein S ( from 19.0 ( 6.0 ) to 40.8 (11.4)% ) increased significantly during the study , whereas both remained reduced in HA- patients . TAT ( indicating intravascular coagulation ) did not differ between the two fluid groups . We conclude that in trauma patients , the type of volume therapy had no influence on the TM-protein C-protein S system . In sepsis patients , volume therapy with HES was beneficial , whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation 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 Objective : There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution ( HES ) in critically ill patients . The effects of volume replacement with HES over 5 days on hemodynamics , laboratory data , and organ function were compared with volume therapy using human albumin ( HA ) . Design : Prospect i ve , r and omized study . Setting : Clinical investigations on a surgical intensive care unit ( ICU ) of a university hospital . Patients : 150 traumatized patients ( injury severity score > 15 ) and 150 postoperative patients with sepsis were analyzed . Interventions : Either 10 % low-molecular weight HES ( HES-trauma , n = 75 ; HES-sepsis , n = 75 ) or 20 % HA ( HA-trauma , n = 75 ; HA-sepsis , n = 75 ) was given for 5 days to maintain the pulmonary capillary wedge pressure ( PCWP ) between 12 and 15 torr . The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen . Measurements and results : In addition to extensive cardiorespiratory monitoring , several routine laboratory parameters for assessing pulmonary , renal , hepatic , and coagulation function were analyzed from arterial blood sample s on the day of admission to the ICU and on the day of sepsis diagnosis , respectively ( “ baseline ” value ) and daily over the following 5 days . Mortality during and after the study did not differ significantly between the infusion groups . There were also no differences between the incidence of pulmonary , renal , or hepatic failure in the two subgroups . Mean arterial pressure , heart rate , and PCWP were similar in both subgroups , whereas cardiac index , oxygen delivery index , oxygen consumption index , and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups . St and ard coagulation parameters did not differ , albumin concentration increased significantly in both HA groups , and lactate concentrations decreased only in the HES-sepsis patients ( from 2.8 ± 0.5 to 1.5 ± 0.4 mg/dl ) . Volume replacement using albumin was significantly ( p < 0.001 ) more costly than therapy with HES . Conclusions : Volume therapy with 10 % HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20 % albumin . Volume replacement using HES may even be associated with improved hemodynamics . HES appears to be a valuable and significantly cheaper alternative to albumin – even for prolonged volume therapy in the critically ill patient UNLABELLED Crystalloids represent an attractive strategy to alleviate intravascular volume deficits . Crystalloid hemodilution was associated with hypercoagulability in in vitro and in vivo studies . The influence of different crystalloids on coagulation in the surgical patient is not well studied . In a prospect i ve , r and omized study in patients undergoing major abdominal surgery , we used either lactated Ringer 's solution ( RL ) ( n = 21 ) or 0.9 % saline solution ( SS ) ( n = 21 ) exclusively for intravascular volume replacement over 48 h to maintain central venous pressure between 8 and 12 mm Hg . Activated thrombelastography ( TEG ) using different activators ( intrinsic TEG , extrinsic TEG , heparinase TEG , aprotinin TEG ) was used to measure coagulation time , clot formation time , and maximum clot firmness . Measurements were performed after induction of anesthesia ( T0 ) , immediately after surgery ( T1 ) , 5 h after surgery ( T2 ) , and on the morning of the first ( T3 ) and second ( T4 ) postoperative days . RL 18,750 + /- 1890 mL and 17,990 + /- 1790 mL of SS were infused during the study period . Acidosis was seen only in the SS-treated group . Blood loss was not different between the groups . Fibrinogen and antithrombin III decreased similarly at T1 and T2 in both groups , most likely because of hemodilution . Differences in TEG data from normal baseline were seen only immediately after surgery and 5 h thereafter , indicating mild hypercoagulability in the intrinsic TEG ( RL , from 147 + /- 130 s to 130 + /- 11 s ; SS , from 146 + /- 12 s to 131 + /- 12 s ) . There were no differences in coagulation between RL- and SS-treated patients . We conclude that in major abdominal surgery intravascular volume replacement with crystalloids result ed in only moderate and abbreviated changes in coagulation . No differences in activated TEG and blood loss were seen between an RL- and an SS-based intravascular volume replacement regimen . IMPLICATION S In 42 patients undergoing major abdominal surgery , either lactated Ringer 's solution or 0.9 % saline solution were exclusively used for volume therapy for 48 h. Activated thrombelastography revealed some mild hypercoagulability after surgery . No differences in coagulation were seen between the two intravascular volume replacement strategies |
567 | 23,728,674 | AUTHORS ' CONCLUSIONS ACTs appear to be safe for individuals ( adults and children ) with stable bronchiectasis , where there may be improvements in sputum expectoration , selected measures of lung function and health-related quality of life .
The role of these techniques in people with an acute exacerbation of bronchiectasis is unknown . | BACKGROUND People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production and these features may be associated with progressive decline in clinical status .
Airway clearance techniques ( ACTs ) are often prescribed to facilitate expectoration of sputum from the lungs , but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear .
OBJECTIVES Primary : to determine the effects of ACTs on the rate of acute exacerbations , incidence of hospitalisation and health-related quality of life in individuals with acute and stable bronchiectasis .
Secondary : to determine whether a ) ACTs are safe for individuals with acute and stable bronchiectasis and b ) ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis . | The relative value of chest physiotherapy ( including cough ) and cough alone for the removal of excessive tracheobronchial secretions has been assessed in six patients with stable chronic obstructive lung disease . After labelling with inhaled radioactive tracer particles , clearance of secretions from selected central and peripheral lung regions was followed with a gamma camera linked to a computer . Cough alone and chest physiotherapy ( including cough ) were equally effective in the enhancement of central lung clearance . Physiotherapy but not cough along accelerated peripheral lung clearance ( p less than 0.05 ) . Sputum yield was greater during physiotherapy than during cough ( p less than 0.05 ) . These findings confirm the value of chest physiotherapy and high-light the limitation of cough in patients with excessive tracheobronchial secretion and impaired mucociliary clearance BACKGROUND Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum . The immunopathology of the disease was studied using a quantitative immunostaining technique with particular reference to T lymphocytes , macrophages , and granulocytes . METHODS Bronchial mucosal biopsy specimens were obtained by fibreoptic bronchoscopy from 12 patients with bronchiectasis ( six receiving inhaled steroids ) and 11 normal healthy controls . Immunostaining ( APAAP method ) was performed on frozen cryostat sections with a panel of monoclonal antibodies to total leucocytes ( CD45 ) , T lymphocyte phenotypic markers ( CD3 , CD4 , CD8 ) , macrophages ( CD68 ) , eosinophils ( EG2 ) , and neutrophils ( elastase ) . RESULTS There was a mononuclear cell infiltrate in both patients with bronchiectasis and normal controls , but an overall increase in total leucocyte cell numbers ( CD45 + cells ) was identified in those with bronchiectasis ( median values 422 cells/mm2 versus 113 cells/mm2 in control tissue , p<0.001 ) . Intense infiltration of CD3 + T lymphocytes was observed compared with healthy controls ( 292 cells/mm2 and 40 cells/mm2 , respectively , p<0.001 ) . This comprised predominantly CD4 + T cells ( 118 cells/mm2 ) rather than CD8 + T cells ( 47 cells/mm2 ) . CD3 + cell counts were reduced in those subjects on inhaled steroids compared with those not receiving inhaled steroids ( 197 cells/mm2 versus 369 cells/mm2 , p<0.05 ) , as were CD4 + cell counts ( 82 cells/mm2 versus 190 cells/mm2 , p<0.05 ) . Neutrophil and macrophage cell numbers were also increased in patients with bronchiectasis ( 114 cells/mm2 and 213 cells/mm2 , respectively ) compared with controls ( 41 neutrophils/mm2 and 40 macrophages/mm2 ) . EG2 + ( activated ) eosinophil numbers were much lower than T cells , macrophages , and neutrophils in patients with bronchiectasis but were increased compared with controls ( 36 cells/mm2 versus 0 cells/mm2 , p<0.001 ) . In view of the markedly increased neutrophil counts in patients with bronchiectasis , biopsy specimens were immunostained for interleukin 8 ( IL-8 ) which was highly significantly increased compared with controls ( 47 cells/mm2 versus 15 cells/mm2 , p<0.01 ) . IL-8 + cells were less prominent in steroid treated patients than in patients not receiving treatment ( 30 cells/mm2 versus 60 cells/mm2 , p<0.05 ) . A further characteristic of bronchiectasis was mucous gl and hypertrophy . Gl and area comprised up to 40 % of the tissue in some bronchiectasis sections while no hypertrophy was noted in control biopsy specimens ( p<0.05 ) . CONCLUSION Airway inflammation in bronchiectasis is characterised by tissue neutrophilia , a mononuclear cell infiltrate composed mainly of CD4 + T cells and CD68 + macrophages , and increased IL-8 expression . Inhaled corticosteroid treatment in patients with bronchiectasis is associated with a less marked infiltration by T cells and IL-8 + cells within the bronchial mucosa , although this finding requires confirmation in a prospect i ve placebo controlled trial Eight patients with Young 's syndrome were treated with four " mucoregulatory " agents for eight weeks in a r and omised , open crossover study . There was no improvement in tracheobronchial clearance , pulmonary function , or sperm count Background Non-cystic fibrosis bronchiectasis is characterised by sputum production , exercise limitation and recurrent infections . Although pulmonary rehabilitation is advocated for this patient group , its effects are unclear . The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity , cough , quality of life and the incidence of acute pulmonary exacerbations . Methods / Design This r and omised controlled trial aims to recruit 64 patients with bronchiectasis from three tertiary institutions . Participants will be r and omly allocated to the intervention group ( supervised , twice weekly exercise training with regular review of airway clearance therapy ) or a control group ( twice weekly telephone support ) . Measurements will be taken at baseline , immediately following the intervention and at six and 12 months following the intervention period by a blinded assessor . Exercise capacity will be measured using the incremental shuttle walk test and the six-minute walk test . Quality of life and health status will be measured using the Chronic Respiratory Question naire , Leicester Cough Question naire , Assessment of Quality of Life Question naire and the Hospital Anxiety and Depression Scale . The rate of hospitalisation will be captured as well as the incidence of acute pulmonary exacerbations using a daily symptom diary . Discussion Results from this study will help to determine the efficacy of supervised twice-weekly pulmonary rehabilitation upon exercise capacity and quality of life in patients with bronchiectasis and will contribute to clinical practice guidelines for physiotherapists in the management of this population .Trial registration This study protocol is registered with Clinical Trials.gov ( NCT00885521 ) BACKGROUND AND PURPOSE Although the application of airway clearance techniques is considered an important component in the treatment of several obstructive pulmonary diseases , there is no scientific evidence supporting the use of Flutter Valve ™ in the management of patients with bronchiectasis . Moreover , the consequences of respiratory physiotherapy techniques on respiratory mechanics have not been fully studied . Therefore , we investigated the acute , short-term effects of Flutter Valve ™ on respiratory mechanics and sputum production in bronchiectatic patients . METHODS EIGHT patients were evaluated in a r and omized , blinded , cross-over trial . Impedance at 5 Hz ( R5 ) , resistance as a function of oscillation frequency ( dR/dF ) , reactance at 5 Hz ( X5 ) , resonant frequency ( f(0 ) ) and integral of reactance between 5 Hz and resonant frequency ( AX ) were recorded . RESULTS Flutter Valve ™ cleared 8.4 mL more secretions than the Sham Flutter intervention ( 95 % confidence interval [ 95 % CI ] , 3.4 - 13.4 ) . There was a higher percentage decrease in R5 ( -11.2 % ; 95 % CI , -4.4 to -18.2 ) , dR/dF ( -20.8 % ; 95 % CI , -32.4 to -9 ) and AX ( -7.8 % ; 95 % CI , -11.9 to -3.7 ) under Flutter Valve ™ . X5 and f(0 ) variation did not differ between interventions . CONCLUSIONS Flutter Valve ™ increases sputum removal during treatment and diminishes total and peripheral airway resistance in hypersecretive patients with bronchiectasis . Impulse oscillometry is a user-friendly tool to evaluate the effects of airway clearance techniques on respiratory mechanics BACKGROUND --In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance . This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique ( FET ) in patients with airways obstruction . METHODS --Nineteen patients ( 11 men and eight women ) of mean ( SE ) age , % predicted FEV1 , and daily sputum wet weight of 64 ( 2 ) years , 52 (6)% , and 37.5 ( 7.9 ) g respectively participated in the study . Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique . Each patient underwent three assessment s : control , cough , and FET . During cough and FET , maximum expiratory flow was measured at the mouth level . Apparent viscosity and elasticity of the expectorated sputum sample s were measured with a viscometer . RESULTS --Compared with the control run ( mean ( SE ) clearance : 16 (3)% ) there was an increase in clearance from the whole lung during cough ( 44 (5)% ) and FET ( 42 (5)% ) , and also an enhanced clearance of inhaled , deposited radioaerosol from the trachea , inner and intermediate regions of the lungs , but not from the outer region . There were , however , no differences in regional clearance between cough and FET . Neither regional nor total clearance correlated with maximum expiratory flow , apparent viscosity , elasticity , or daily sputum wet weight . CONCLUSIONS --These results confirm that cough and FET both promote effective clearance but suggest that , unlike in vitro studies , sputum production and viscoelasticity , as well as maximum expiratory flow , provide no guide to clearance efficacy in humans Background : Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation , and leading to decreased exercise tolerance and reduced health status . The role of pulmonary rehabilitation ( PR ) and inspiratory muscle training ( IMT ) has not been investigated in this group of patients . Methods : Thirty two patients with idiopathic bronchiectasis were r and omly allocated to one of three groups : PR plus sham IMT ( PR-SHAM ) , PR plus targeted IMT ( PR-IMT ) , or control . All patients ( except the control group ) underwent an 8 week training programme of either PR or PR plus targeted IMT . Exercise training during PR was performed three times weekly at 80 % of the peak heart rate . IMT was performed at home for 15 minutes twice daily over the 8 week period . Results : PR-SHAM and PR-IMT result ed in significant increases in the incremental shuttle walking test of 96.7 metres ( 95 % confidence interval ( CI ) 59.6 to 133.7 ) and 124.5 metres ( 95 % CI 63.2 to 185.9 ) , respectively , and in endurance exercise capacity of 174.9 % ( 95 % CI 34.7 to 426.1 ) and 205.7 % ( 95 % CI 31.6 to 310.6 ) . There were no statistically significant differences in the improvements in exercise between the two groups . Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group ( 21.4 cm H2O increase , 95 % CI 9.3 to 33.4 ; p = 0.008 ) and the PR-SHAM group ( 12.0 cm H2O increase , 95 % CI 1.1 to 22.9 ; p = 0.04 ) , the magnitude of which were also similar ( p = 0.220 ) . Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training , but not in the PR-SHAM group . Conclusion : PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT . IMT may , however , be important in the longevity of the training effects Educational aims To describe the specific current and potential future treatments for bronchiectasis . To describe a potential management plan for the treatment of bronchiectasis . Summary Non-cystic fibrosis ( non-CF ) bronchiectasis remains a common and difficult respiratory condition to manage . Patients with bronchiectasis generally tend to have persistent symptoms and require long-term medical treatment . There are a large number of treatment options available for the management of bronchiectasis . However only a limited number of trials to assess efficacy of treatment have been conducted . These studies have generally included fewer than 20 patients and very few of them have been r and omised or blinded . As such , the management of bronchiectasis is not clearly defined . This review will discuss the specific treatments available to treat patients with non-CF bronchiectasis and how they could be integrated into a specific management plan AUTHOR : e-mail address please Background : Airway clearance techniques are an important part of the routine care of patients with bronchiectasis . The use of the Flutter , a h and held pipe-like device causing oscillating positive expiratory pressure within the airways , has been proposed as an alternative to more conventional airway clearance techniques . Methods : A r and omised crossover study was performed in 17 stable patients with non-cystic fibrosis bronchiectasis at home , in which 4 weeks of daily active cycle of breathing technique ( ACBT ) were compared with 4 weeks of daily physiotherapy with the Flutter device . Results : No significant differences between the two techniques were found . Median weekly sputum weights were similar with a median treatment difference of 7.64 g ( p=0.77 ) and there was no evidence of treatment order or order interaction effects ( p=0.70 ) . Health status ( Chronic Respiratory Disease Question naire ) and ventilatory function did not change significantly during either treatment period . There was no significant change in peak expiratory flow rate or in breathlessness ( Borg score ) after individual physiotherapy sessions with either technique . A question naire indicated subjectively that patients preferred the Flutter ( 11/17 ) to ACBT for routine use . Conclusions : Daily use of the Flutter device in the home is as effective as ACBT in patients with non-cystic fibrosis bronchiectasis and has a high level of patient acceptability Regular chest physiotherapy is advocated in non-cystic fibrosis bronchiectasis despite little evidence supporting its routine use . This study aim ed to establish the efficacy of regular chest physiotherapy in non-cystic fibrosis bronchiectasis compared with no regular chest physiotherapy . 20 patients not practising regular chest physiotherapy were enrolled in a r and omised crossover trial of 3 months of twice daily chest physiotherapy using an oscillatory positive expiratory pressure device compared with 3 months of no chest physiotherapy . The primary end-point was the Leicester Cough Question naire ( LCQ ) . Additional outcomes included 24-h sputum volume , forced expiratory volume in 1 s ( FEV1 ) , forced vital capacity ( FVC ) , forced expiratory flow at 25–75 % of FVC ( FEF25–75 % ) , maximum inspiratory pressure ( MIP ) , maximum expiratory pressure ( MEP ) , exercise capacity , sputum microbiology and St George 's Respiratory Question naire ( SGRQ ) . The treatment effect was estimated using the differences of the pairs of observations from each patient . There was a significant improvement in all domains and total LCQ score with regular chest physiotherapy ( median ( interquartile range ) total score improvement 1.3 ( -0.17–3.25 ) units ; p = 0.002 ) . 24-h sputum volume increased significantly with regular chest physiotherapy ( 2 ( 0–6 ) mL ; p = 0.02 ) , as did exercise capacity ( 40 ( 15–80 ) m ; p = 0.001 ) and SGRQ total score ( 7.77 ( -0.99–14.5 ) unit improvement ; p = 0.004 ) . No significant differences were seen in sputum bacteriology , FEV1 , FVC , FEF25–75 % , MIP or MEP . Regular chest physiotherapy in non-cystic fibrosis bronchiectasis has small , but significant benefits Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus . A 400-mg dose of inhaled mannitol improves mucus clearance however , the effect of other doses is unknown . A total of 14 patients , aged 63.3±5.7 yrs , were studied on five visits . Mucus clearance at baseline and with mannitol ( 160 , 320 and 480 mg ) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min , followed by a further 30 min involving 100 voluntary coughs . A control study assessed the effect of cough provoked by mannitol during the intervention . Whole right lung clearance over 45 min was 4.7±1.2 and 10.6±2.6 % on baseline and control days , respectively , and increased to 16.7±4.2 , 22.8±4.2 and 31±4.7 % with 160 , 320 and 480 mg mannitol , respectively . Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg . Total clearance over 75 min , after mannitol administration and voluntary coughs , was 36.1±5.5 , 40.9±5.6 and 46.0±5.2 % with 160 , 320 and 480 mg mannitol , respectively , all significantly different from baseline ( 24.1±6.0 % ) and control ( 13.1±3.0 % ) . Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg . In conclusion , mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis Question For patients with bronchiectasis , does pulmonary rehabilitation either with or without inspiratory muscle training ( IMT ) improve exercise tolerance ? Design R and omised controlled trial . Setting Outpatient-based pulmonary rehabilitation program of a UK hospital . Patients Patients with bronchiectasis confirmed by highresolution computer tomography . Exclusion criteria included concomitant emphysema , an acute exacerbation in the previous six weeks , long-term oral corticosteroid use , and significant co-morbidities . Thirty-two patients were r and omised to pulmonary rehabilitation plus IMT ( PRIMT ) ( n = 12 ) , pulmonary rehabilitation plus sham IMT ( PR-Sham ) ( n = 11 ) , or a control group with no intervention ( n = 9 ) . Interventions Pulmonary rehabilitation consisted of exercise training and multidisciplinary education sessions for eight weeks . Exercise consisted of three 45- minute periods per week with a target exercise intensity of 80 % of the peak heart rate achieved on an initial maximal incremental exercise test . Two sessions per week were performed at the hospital and involved cycling , treadmill walking , and stair climbing . A third session of walking was performed at home , using the Borg dyspnoea scale to guide intensity . IMT was performed for 15 minutes twice daily over the eight-week period using a pressure threshold device . Pressure was set at 30 % of the patient 's maximal inspiratory pressure and increased by 5 % each week to a maximum of 60 % . Sham IMT followed the same regimen except that the pressure was always 7 cmH 2 O. Outcomes The incremental shuttle walk test , endurance exercise capacity , and respiratory muscle strength were assessed in all groups at baseline and at the end of the program . The endurance exercise test involved walking on a treadmill at 85 % of peak oxygen uptake . Results Over the eight weeks , improvement in the incremental shuttle walk test was significantly greater in the PR-IMT group ( by 113 m , 95 % CI 45 to 182 ) and PRSham group ( by 86 m , 95 % CI 42 to 130 ) than the control group . Similarly , change in endurance exercise capacity was significantly better in the PR-IMT group ( by 720 m , 95 % CI 342 to 1098 ) and PR-Sham group ( by 505 m , 95 % CI 128 to 883 ) than the control group . Change in maximal inspiratory pressure was significantly better in the PR-IMT group ( by 23 cmH 2 O , 95 % CI 10 to 36 ) and the PR-Sham group ( by 14 cmH 2 O , 95 % CI 2 to 25 ) than that seen in the control group . The inclusion of IMT did not produce a statistically significant benefit over pulmonary rehabilitation alone for these outcomes during the training period . Conclusion Pulmonary rehabilitation with or without IMT improves exercise tolerance and inspiratory muscle strength in subjects with bronchiectasis BACKGROUND : Treatment of bronchiectasis includes drugs , oxygen therapy , and bronchial-clearance maneuvers . OBJECTIVE : To assess the safety and efficacy of intrapulmonary percussive ventilation ( IPV ) compared to traditional st and ard chest physical therapy in patients with bronchiectasis and productive cough . METHODS : In a r and omized crossover study , 22 patients underwent , on consecutive days , IPV and chest physical therapy . Before each treatment session , immediately after the session , 30 min after the session , and 4 hours after the session we measured SpO2 , heart rate , respiratory rate , and ( with a visual analog scale ) the patient 's subjective sensation of phlegm encumbrance and dyspnea . Immediately after each treatment session we also measured ( via visual analog scale ) the patient 's discomfort . We also measured the volume and wet and dry weight of collected sputum . RESULTS : No adverse effects were so severe as to require discontinuation of treatment , and the incidence of adverse effects was similar in the groups ( 27 % ) . Heart rate ( P = .002 ) and respiratory rate ( P = .047 ) decreased during treatment , and sensation of phlegm encumbrance improved ( P = .03 ) with both treatments . Only IPV improved ( P = .004 ) the sensation of dyspnea . The patients found IPV more comfortable than our traditional st and ard chest physical therapy ( P = .03 ) . Both treatments caused important phlegm production , but there were no differences in sputum volume , wet weight , or dry weight . CONCLUSIONS : In patients with bronchiectasis and productive cough , short-term IPV was as safe and effective as traditional chest physical therapy , with less discomfort Humidification of inspired air or oxygen is frequently utilized by respiratory physiotherapists to relieve sputum retention . Cold water , jet nebulizing humidifiers are in widespread use but there has been no previous attempt to investigate the efficacy of this treatment . We have performed a single-blind , cross-over study to quantify the effect of humidification as an adjunct to chest physiotherapy . Seven patients with bronchiectasis completed the trial , with a mean ( range ) age of 51 years ( 41 - 64 years ) and mean ( range ) percent of predicted FEV1 of 46 % ( 29 - 76 % ) . On 2 days , separated by 1 week , subjects were r and omly allocated to humidification or no humidification as a precursor to an optimal chest physiotherapy regimen . A radio-aerosol of human serum albumin millimicrospheres labelled with 99mTechnetium was used to measure sputum clearance by serial gamma camera images . Serial measurements of sputum weight and FEV1 were also recorded . Humidification ( 30 min ) was followed by postural drainage ( 20 min ) with the subject using the forced expiration technique to assist clearance . When humidification was combined with physiotherapy there was a significant increase in total wet weight of sputum ( P less than 0.05 ) with a median ( range ) increase of 6 g ( -9 - 15.5 g ) ; and a significant increase in total radiolabel clearance ( P less than 0.05 ) with a median ( range ) increase of 8.7 % ( 1 - 13 % ) , compared to physiotherapy alone . This study demonstrates that the use of cold water , jet nebulizing humidifiers significantly increases tracheo-bronchial clearance above that of an optimal physiotherapy regimen alone in bronchiectasis . ( ABSTRACT TRUNCATED AT 250 WORDS Chronic productive cough is a common symptom in patients with bronchiectasis that is associated with a reduction in health-related quality of life ( QOL ) . Bronchopulmonary hygiene physical therapy ( BHPT ) is widely prescribed for patients with bronchiectasis , although the evidence for its efficacy is limited . We set out to prospect ively evaluate the impact of BHPT on health-related QOL in patients with non-cystic fibrosis bronchiectasis . We assessed cough symptoms ( 0 - 100 mm visual analogue scale ; VAS ) and cough-related QOL in 53 patients with stable non-cystic fibrosis bronchiectasis at baseline and > 4 weeks after outpatient-based BHPT . Cough specific health status was assessed with the Leicester Cough Question naire ( LCQ ; total score range 3 - 21 , higher scores representing better QOL ) . All patients with bronchiectasis complained of cough as the major symptom and had mean ( SEM ) FEV(1 ) of 2.1 (0.1)L. Cough-related health status was reduced at baseline ; mean ( SEM ) LCQ score 14.3 ( 0.6 ) . There were significant improvements in cough symptoms ( mean cough VAS before 43.3 ( 3.6 ) vs after 27.5 ( 3.1 ) ; mean difference 15.8 ; 95 % CI of difference 9.6 - 22 ; p<0.0001 ) and cough-related health status after BHPT ( mean LCQ total score before 14.2 vs after 17.3 ; mean difference 3.1 ; 95 % confidence interval of difference 2.4 - 3.9 ; p<0.001 ) . A significant improvement was seen in all LCQ health-related domains ( physical , psychological and social ; all p<0.001 ) . Our findings suggest that bronchopulmonary hygiene physical therapy can lead to a significant improvement in cough-related quality of life Airway clearance is integral to the management of bronchiectasis , yet there is no evidence as to the optimal modality . The aim of this r and omized prospect i ve study was to evaluate the acute efficacy , acceptability and tolerability of three airway clearance techniques in non-cystic fibrosis ( non-CF ) bronchiectasis . Flutter , active cycle of breathing technique ( ACBT ) and ACBT with postural drainage ( ACBT-PD ) were evaluated in r and om order over a week in 36 patients ( mean age 62 years , range 33 - 83 ) , with stable non-CF bronchiectasis . Total sputum wet weight for ACBT-PD was twice that of either ACBT alone or Flutter . No objective difference in treatment duration was noted . All three techniques were well accepted and tolerated . Patient preference was 16 ( 44 % ) for Flutter , eight ( 22 % ) ACBT and 12 ( 33 % ) for ACBT-PD . Patient demography , factors such as upper airways or reflux symptoms , previous use or acute efficacy did not predict preference . This is the first r and omized systematic evaluation of acute efficacy , acceptability and tolerability of Flutter , ACBT and ACBT-PD in non-CF bronchiectasis . All three techniques were well tolerated but ACBT-PD proved superior in terms of acute efficacy . Patient preference for treatment modality could not be predicted Objectives : The purpose of this study was to compare the efficacy of the test of incremental respiratory endurance ( TIRE ) with active cycle of breathing techniques ( ACBT ) [ incorporating postural drainage ( PD ) and vibration ] as methods of airway clearance in adults with bronchiectasis . Design : A r and omized crossover study in which a single session of ACBT ( incorporating PD and vibration ) was compared to a single session of TIRE was carried out in 20 patients ( 14 female ) with stable , productive bronchiectasis . Measurements : Weight of sputum ( treatment plus 30 min ) was the primary outcome measure recorded . Pre and post-treatment measures of lung function and SpO2 were also recorded . Results : All 20 patients were stable during the study period . Sputum weight expectorated during and 30 min post-ACBT ( incorporating PD and vibration ) treatment was significantly greater than the sputum weight expectorated during and 30 min post-TIRE treatment [ mean difference 2.44 g ( 95 % CI 0.43 - 4.45 ) ] . Conclusion : ACBT ( incorporating PD and vibration ) is a more effective method of airway clearance in bronchiectasis than TIRE during single treatment sessions Devices such as the Acapella ® may facilitate independent airway clearance , however , few clinical trials have investigated the efficacy of Acapella ® . The aim of this study was to compare the effectiveness of Acapella ® to ` usual airway clearance ' in adults during an acute exacerbation of bronchiectasis requiring oral antibiotic therapy . Twenty patients with bronchiectasis and an acute exacerbation requiring oral antibiotic therapy were recruited into a r and omized crossover trial . Patients were allocated to one of two groups determined by concealed computer generated r and omization . Group 1 ( n = 10 ) : airway clearance session using Acapella ® at home twice daily during oral antibiotic therapy . Group 2 ( n = 10 ) : ` usual ' airway clearance sessions at home during oral antibiotic therapy . Patients recorded duration of each treatment session , volume of sputum produced and perception of breathlessness . An independent assessor performed outcome measures of spirometric lung function , pulse oximetry and breathlessness at the beginning and end of the study period . The mean volume of sputum expectorated during Acapella ® sessions was greater than for usual airway clearance sessions although this difference was not significant 2.61 ml ( 95 % CI-1.62 to 6.84 ) . Mean duration of Acapella ® sessions was greater than usual airway clearance sessions and approached significance . There were no significant between group differences in changes in lung function . This study demonstrates that the Acapella ® device may offer an acceptable , user-friendly method of airway clearance in patients with bronchiectasis . Chronic Respiratory Disease 2007 ; 4 : Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease . In a previous study we demonstrated that nebulised 7 % hypertonic saline was both safe and effective in this patient population . Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis , confirmed by H RCT , were entered into a r and omised single blind cross-over study to evaluate 0.9 % sodium chloride ( IS ) and 7 % hypertonic saline ( HS ) . Following a 4 week run in patients received a r and om order active HS or IS daily for 3 months . A 4 week wash-out phase was included between phases . We report lung function , quality of life , and health care utilisation responses . 32 patients mean age 56.6 years ( SD 14.6 ) , 16 male , were recruited of which 28 were r and omised and completed the study . Lung function ( % change from baseline ) improved in HS vs. IS ( FEV(1 ) : 15.1 , 1.8 p<0.01 ; FVC : 11.2 , 0.7 p<0.01 . SGRQ improved significantly from baseline ( HS 6.0 , IS 1.2 ; p<0.05 ) . There were reductions in annualised antibiotic usage ( HS 2.4 , IS 5.4 courses per patient per year ) , annualised emergency health care utilisation visits were reduced ( HS 2.1 , IS 4.9 events per patient per year ) . There were also improvements in sputum viscosity and ease of expectoration ( visual analogue scale ) . Regular use of 7 % hypertonic saline improves lung function , quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients Sputum clearance is of prime importance in the management of patients with bronchiectasis . While nebulised normal isotonic saline ( 0.9 % ) ( IS ) has been anecdotally used to treat patients with tenacious sputum , the use of hypertonic saline ( 7 % ) ( HS ) could have potential muco-protective and clearance properties . 24 patients with bronchiectasis were r and omised to receive four single treatment schedules in r and om order : ( 1 ) active cycle breathing technique ( ACBT ) alone , ( 2 ) nebulised terbutaline then ACBT , ( 3 ) nebulised terbutaline , nebulised IS then ACBT and ( 4 ) nebulised terbutaline , nebulised HS then ACBT . Sputum weights were significantly higher after HS than IS ( P = 0.002 ) . Ease of expectoration also differed overall ( P < 0.0001 ) and was significantly lower with HS than with IS ( P = 0.0005 ) . Sputum viscosity differed between treatment phases , with a significant linear trend to reduced sputum viscosity with HS ( P = 0.0002 ) . These changes were associated with small but statistically significant differences in FEV1 ( P = 0.043 ) and FVC ( P = 0.011 ) between treatment phases . Nebulised hypertonic saline can be used safely and effectively as an adjunct to physiotherapy in selected patients . A long-term prospect i ve trial is now indicated to determine its effectiveness on long-term infection rate , quality of life and lung function Objective : To evaluate whether temporary positive expiratory pressure provides benefit in patients with lung diseases and chronic hypersecretion . Design : Single blind multicentre r and omized trial . Setting : Five Italian rehabilitation centres . Participants : Ninety-eight patients with chronic obstructive pulmonary disease and /or chronic bronchitis ( n=78 ) , or bronchiectasis ( n=20 ) , with a peak cough expiratory flow > 150 l/min and sputum production > 30 ml/day , r and omly included into two treatment groups . Interventions : For 10 consecutive days , the active group performed twice a day 20-minute cycles of manually assisted breathing techniques in sequence with the addition of 15 minutes of temporary positive expiratory pressure , while the control group was treated by manually assisted breathing techniques alone . Measures : Within and between group changes of arterial oxygenation index , lung volumes and respiratory muscles strength were recorded at enrolment and after 3 and 10 treatment sessions . Pre-to-post treatment change of sputum volume and bronchial encumbrance ( Δ-visual analog scale ) , sputum density and purulence were compared daily within the study period . Results : No significant changes were recorded for the oxygenation index , while dynamic lung volumes and respiratory muscle strength significantly ( P < 0.05 ) improved in the active group . The group comparison analysis of the pre-to-post change showed that inspiratory capacity was significantly higher in the active than in the control group ( + 19.5 % and + 2.2 % , P=0.044 ) at day 10 . A greater improvement in Δ-visual analog scale was recorded in the active group at day 3 and 8 . Conclusions : These preliminary data suggest that temporary positive expiratory pressure improves lung volumes and speeds up the improvement of bronchial encumbrance in patients with lung diseases and hypersecretion BACKGROUND The Flutter( ® )VRP1 combines high frequency oscillation and positive expiratory pressure ( PEP ) . OBJECTIVE To separately evaluate the effect of the Flutter( ® )VRP1 components ( high frequency oscillation and PEP ) on mucus transportability in patients with bronchiectasis . METHODS Eighteen patients with bronchiectasis received sessions with the Flutter( ® )VRP1 or PEP for 30 min daily in a r and omized , crossover study . The treatment duration was four weeks with one of the therapies , one week of a " wash-out " period and followed by four more weeks with the other treatment . Weekly secretion sample s were collected and evaluated for mucociliary relative transport velocity ( RTV ) , displacement in a simulated cough machine ( SCM ) and contact angle measurement ( CAM ) . For the proposed comparisons , a linear regression model was used with mixed effects with a significance level of 5 % . RESULTS The Flutter( ® )VRP1 treatment result ed in greater displacement in SCM and lower CAM when comparing results from the first ( 9.6 ± 3.4 cm and 29.4 ± 5.7 ° , respectively ) and fourth weeks of treatment ( 12.44 ± 10.5 cm and 23.28 ± 6.2 ° , respectively ; p < 0.05 ) . There was no significant difference in the RTV between the treatment weeks for either the Flutter( ® )VRP1 or PEP . CONCLUSION The use of the Flutter( ® )VRP1 for four weeks is capable of altering the respiratory secretion transport properties , and this alteration is related to the high frequency oscillation component OBJECTIVES The proteolytic enzyme serrapeptase ( SER ) is widely used in clinical practice in Japan . We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases . METHODS This study was an open-labelled trial with a non-treatment control group . Patients were r and omly assigned to oral treatment with ( n = 15 ) and without ( n = 14 ) SER 30 mg/day for 4 weeks . Patients collected sputum sample s for about 4 h in the morning on the day the trial began and 4 weeks later . We measured the amount of sputum by weighing . Part of each sputum sample was weighed and then completely dried and reweighed . The percentage solid component , viscosity and elasticity of the sputum were measured . Mucociliary transportability index was measured using ciliated bovine trachea ex vivo . Sputum smears were also prepared to count sputum neutrophils . Patients ' symptoms were assessed by a question naire that used a visual analogue scale . RESULTS After 4 weeks of SER treatment , sputum weight in the morning , percentage solid component , viscosity and elasticity of sputum , sputum neutrophil count , frequency of coughing and frequency of expectoration significantly decreased . The mean mucociliary transportability index increased from 13.3 + /- 1.8 to 24.4 + /- 2.5 ( P = 0.0103 ) . CONCLUSIONS SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases AIMS AND OBJECTIVES To examine and compare the effects of acupressure on the perceived health-related quality of life of the participants with bronchiectasis . BACKGROUND In an attempt to offer comfort , pain control and symptom management , nursing is becoming increasingly involved in offering complementary-alternative medicine as part of its caring-healing focus in comprehensive patient care . Acupressure is one such modality that is being increasingly used by both medical and nursing professionals . While acupressure has been reported to have beneficial effects in patients with respiratory disease , the benefits to bronchiectasis patients have remained uncertain . DESIGN A r and omized , partially blinded study consisting of three groups . METHODS Thirty-five out- patients of both genders , aged 59.46 SD 11.52 years , who were suffering from bronchiectasis , were r and omly split into one of three groups : st and ard care with supplemental acupressure for eight weeks ( 11 participants ) ; st and ard care with supplemental sham acupressure for eight weeks ( 11 participants ) ; and st and ard care alone ( 13 participants ) . Outcomes were determined by changes in daily sputum amounts , sputum self- assessment , six-minute walking distance , breathing difficulty ( measured on the dyspnea visual analogue scale ) and health-related quality of life ( measured by the Saint George Respiratory Question naire ) . RESULTS The sputum self- assessment score improved over time for the sham acupressure participants ( P = 0.03 ) , when compared with the controls . For acupressure participants , the Saint George respiratory question naire activity component scores also improved over time , compared with controls ( P = 0.01 ) after adjustment for covariates ( treatment , time , age , sex and baseline values ) . Other variables did not differ between the st and ard care alone group and the other two groups . CONCLUSIONS Eight weeks of self-administered acupressure could be useful in reducing the effects of bronchiectasis on a patient 's daily activities . RELEVANCE TO CLINICAL PRACTICE Acupressure may be regarded as a viable nursing intervention Background : The efficacy of a new airway clearance device ( Acapella ® ) has not been previously investigated . Active cycle of breathing techniques ( ACBT ) is the st and ard airway clearance technique used in patients with bronchiectasis . Objective : The objective of this study was to compare the efficacy of ACBT with Acapella as methods of airway clearance in adults with stable , productive bronchiectasis . Methods : Twenty patients ( 7 males ) , age 58 ± 11 years ( mean ± SD ) , FEV1 64 ± 22 % predicted with stable ( change of not greater than FEV1 10 % predicted during 3 months prior to study ) , productive ( history of expectoration of half an egg cup sputum/day ) bronchiectasis attended the respiratory clinic on 3 days . Day 1 : 40-min training session on ACBT and Acapella . Days 2 and 3 : 30-min treatment session of either ACBT or Acapella . Treatment order was determined by a concealed r and omization procedure . The following outcomes were measured before and after treatment spirometry , SpO2 and breathlessness by an independent assessor who was blinded to treatment order . Weight of sputum ( during treatment plus 30 min after treatment ) , number of coughs and patient preference were also recorded . Results : No significant differences were found at baseline indicating that patients were stable . No significant differences were found between weight of sputum expectorated with ACBT treatment and weight of sputum expectorated with Acapella treatment – mean difference 0.54 g ( 95 % CI –0.39 to 1.46 ) . A greater proportion of patients preferred Acapella ( 14/20 ) . Conclusion : Acapella is as effective a method of airway clearance as ACBT and may offer a user-friendly alternative to ACBT for patients with bronchiectasis STUDY OBJECTIVE To study the safety and efficacy of aerosolized recombinant human DNase I in the treatment of idiopathic bronchiectasis . DESIGN Double-blind , r and omized , placebo-controlled , multicenter study . POPULATION S Three hundred forty-nine adult out patients in stable condition with idiopathic bronchiectasis from 23 centers in North America , Great Britain , and Irel and . INTERVENTIONS AND MEASUREMENTS Study patients received aerosolized rhDNase or placebo twice daily for 24 weeks . Primary end points were incidence of pulmonary exacerbations and mean percent change in FEV1 from baseline over the treatment period . RESULTS Pulmonary exacerbations were more frequent and FEV1 decline was greater in patients who received rhDNase compared with placebo during this 24-week trial . CONCLUSIONS rhDNase was ineffective and potentially harmful in this group of adult out patients in stable condition with idiopathic bronchiectasis . This contrasts with previously published results that demonstrated efficacy of rhDNase in patients with cystic fibrosis bronchiectasis The outcome in adult bronchiectasis has not been well described ; in particular there has been a lack of long-term prospect i ve studies . Therefore a follow-up study was performed to assess outcome in bronchiectasis in a cohort of adult patients . One hundred- and -one sequential adults , 33 male and 68 female ; age 54 ± 14 years ( mean ± SD ) with bronchiectasis had a clinical assessment and spirometry performed . All were non-smokers and 84 were classified as having idiopathic disease . Patients were commenced on a st and ardized treatment regime and followed up for a minimum period of 2 years . On their last review when patients were clinical ly stable , a repeat clinical assessment and spirometry was performed and compared with the initial review . The primary endpoints measured were symptoms and FEV1 . Subjects were followed up for 8.0 ± 4.9 years . Clinical review showed that the patients had persistent symptoms that , in the case of dyspnea and sputum volume , were worse on follow-up . Spirometry showed a significant decline in FEV1 over the follow-up period with an average loss of 49 ml per year . This study showed in this group of predominantly female adult patients with bronchiectasis followed up for 8 years , patients had persistent symptoms and an excess loss in FEV1 BACKGROUND Mucus plugging and hypersecretion have been associated with an increased relative risk of death in patients with bronchiectasis who may or may not have chronic obstructive pulmonary disease ( COPD ) , which is of prognostic relevance in the elderly . However , chest physiotherapy and /or the use of mucoactive agents is considered to be an effective therapeutic model in treating patients with COPD and bronchiectasis . OBJECTIVE The objective of this study was to test the effectiveness of oral erdosteine in treating elderly patients with bronchiectasis and chronic mucus hypersecretion who have been referred to a pulmonary rehabilitation program . METHODS In this 15-day , prospect i ve , parallel , open label , pilot study , elderly patients with bronchiectasis , hypersecretion , a noncurrent smoking status , who had been consecutively enrolled at Ospedale Villa Pineta 's Pulmonary Rehabilitation Center , Pavullo-Modena , Italy , were r and omized into 2 treatment groups . Group 1 consisted of those patients receiving PO erdosteine 225 mg BID and chest physiotherapy ; group 2 comprised those patients receiving chest physiotherapy alone . Forced lung volumes , arterial blood gases , respiratory muscle strength , walking capacity ( as measured by 6-minute walking test [ 6MWT ] ) , and visual analog scale ( VAS ) symptoms ( cough and dyspnea ) were recorded at enrollment and at the conclusion of the study . Mucus density ( MD ) , mucus purulence ( MP ) , and mucus volume produced ( MVP ) were assessed using a 3-point scale ( 0 = best or low ; 1 = moderate ; and 2 = worst or high ) at baseline and at 5-day time points during the study period . All measurements were assessed by personnel blinded and not directly associated with the study administration . RESULTS Thirty patients ( 21 [ 70 % ] male and 9 [ 30 % ] female ; mean [ SD ] age , 71 [ 11 ] years ; and mean [ SD ] weight , 66 [ 3 ] kg ) were enrolled . Characteristics were similar in the 2 groups at baseline . At day 15 , significant improvements were observed in 6MWT , VAS cough , and VAS dyspnea ( P < 0.01 ) in both groups . However , a significant improvement in forced expiratory volume in 1 second and forced vital capacity ( in milliliters ) was observed only in group i ( 0.2 [ 0.3 ] ; P < 0.05 ) . At day 15 , improvement was observed in mean ( SD ) in MD , MP , and MVP scores for both groups . Significant changes , however , were observed in all 3 measurements in group 1 ( -0.80 [ 0.22 ] , -0.71 [ 0.51 ] , and 1.01 [ 0.39 ] , respectively ) , whereas a significant improvement was observed only in MD ( -0.55 [ 0.44 ] ) and MVP ( 0.45 [ 0.62 ] ) in group 2 . The improvement in MVP observed in group 1 was significantly better than that observed in group 2 ( P < 0.05 ) . CONCLUSION This pilot study found that a regimen of PO erdosteine 225 mg BID in addition to routine chest physiotherapy provided some physiologic and clinical benefits in the treatment of these elderly patients with bronchiectasis and chronic mucus hyper-secretion The active cycle of breathing techniques ( ACBT ) in gravity-assisted drainage positions is an effective airway clearance regimen for individuals who produce excess bronchial secretions . This study compared the ACBT in positions with and without a head-down tilt . Nineteen subjects ( 11 men ) , mean age 37.1 years ( range 18 - 76 years ) , with bronchiectasis who produced more than 20 g of sputum per day and had a mean forced expiratory volume in 1 s ( FEV1 ) of 56.9 % predicted ( range 23 - 90 % pred . ) were studied . There was no significant difference in the wet weight of sputum expectorated when using the ACBT in gravity-assisted drainage positions with or without a head-down tilt . Mean ( SD ) score for perception of breathlessness , measured on a visual analogue scale , increased significantly following treatment with a head-down tilt [ 2.3 ( 1.6 ) to 3.3 ( 2.0 ) cm , P = 0.02 ] . There was no significant difference in oxygenation or lung function ( FEV1 ) . Eighteen subjects preferred the ACBT without a head-down tilt . The ACBT in the horizontal position is a simple airway clearance regimen suitable for individuals who produce greater than 20 g of sputum per day . Subjects were less breathless and preferred the ACBT in the horizontal position , thus providing a treatment alternative that may improve adherence in individuals who are required to carry out daily airway clearance treatments The effect of manual chest percussion was studied in nine patients with copious sputum production . Treatment consisting of postural drainage ( PD ) and the forced expiration technique ( FET ) produced sputum at the rate of 0.831 g min-1 . When percussion was included in the treatment regimen , the rate of sputum production was significantly greater ( P less than 0.05 ) , being 1.231 g min-1 for fast percussion and 1.040 g min-1 for slow percussion . Pulmonary function and oxygen saturation were unaffected by any of the treatment regimens . This study demonstrates that manual chest percussion is a useful adjunct to PD and FET in the treatment of patients with copious sputum production Primary ciliary dyskinesia ( PCD ) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance . Because patients with PCD use cough clearance as an airway defense mechanism , we tested the hypothesis that aerosolized uridine-5'-triphosphate ( UTP ) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells . We measured clearance during cough in 12 patients with PCD ( ages 14 to 71 yr , FEV1 43 % to 89 % predicted ) in a double blind , r and omized , crossover study after aerosolization of a single dose of UTP ( 5 mg/ml , 3.5 ml ) or vehicle ( 0.12 % saline , 3.5 ml ) . Clearance during cough ( whole lung ) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min . Safety parameters were recorded during and after drug delivery . Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle ( from 0 to 60 min : 0.40 + /- 0.07%/min [ UTP ] versus 0.26 + /- 0 . 04%/min [ vehicle ] [ mean + /- SEM ] , p = 0.01 ) , and from 0 to 120 min : 0.38 + /- 0.05%/min [ UTP ] versus 0.25 + /- 0.04%/ min [ vehicle ] , p = 0 . 02 ) . Aerosolized UTP is safe , with no serious adverse effects . Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP BACKGROUND AND OBJECTIVE Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis . A reduction in FEV1 has been recorded in some subjects with bronchiectasis after inhaling mannitol . The aim of this study was to investigate if pre-medicating with either sodium cromoglycate ( SCG ) or eformoterol could inhibit this reduction in FEV1 . METHODS A double-blind , placebo-controlled , r and omized cross-over study was conducted . Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo , SCG and eformoterol in nine subjects . Sensitivity to mannitol , expressed as the dose required to induce a 15 % fall in FEV1 ( PD15 ) , and reactivity to mannitol , expressed as the % fall in FEV1 per mg of mannitol ( response-dose ratio , RDR ) , are reported . RESULTS Subjects had an FEV1 of 68 ± 14 % predicted , FVC of 97 ± 15 % predicted and FEV1 /FVC of 71 ± 8 % . They were mildly hypoxemic and the SpO2 was 95 ± 2%.They had a PD15 to mannitol of 235 mg ( 95 % CI : 150 - 368 mg ) and a RDR of 0.057 % fall in FEV1 per mg ( 95 % CI : 0.038 - 0.085 ) . After pre-medication with SCG , PD15 increased ( 773 mg , P < 0.05 ) and RDR was reduced ( 0.013 , P < 0.05 ) . Pre-medication with eformoterol also result ed in an increased PD15 ( 1141 mg , P < 0.01 ) and a reduced RDR ( 0.009 , P < 0.01 ) . A small but significant decrease in SpO2 from baseline was noted after mannitol in the presence of SCG ( P < 0.05 ) . CONCLUSIONS Pre-medication with either SCG or eformoterol protects patients with bronchiectasis from developing a significant reduction in FEV1 after inhaling mannitol Background : Inspiratory muscle training is used to specifically strengthen the respiratory muscles . Controversy exists regarding the use of inspiratory muscle training as a method of facilitating airways clearance . Acapella is already known to be effective in airway clearance . Objective : The objective of the study was to compare the effects of the Acapella and a threshold inspiratory muscle trainer as a method of airway clearance in subjects with bronchiectasis and to determine patient preference between the two techniques . Methods : Thirty patients ( 10 males , 20 females ) mean age of 50.67±6.37 ( mean±SD ) with a history of expectoration of more than 30 ml sputum per day were recruited . The sequence of therapy was allocated by block r and omization . Assessment and familiarization session was perfomed on day 1 . Treatments employing the Acapella and inspiratory muscle trainer were done on days 2 and 3 . Treatment order and allocation was determined by block r and omization . Sputum volume was measured during and 2 hours after the treatment and patient treatment preference was recorded . Results : A statistically significant difference was found in the sputum volume expectorated after treatment with the Acapella ( 7.16±1.12 ml ) compared with the threshold inspiratory muscle trainer ( 6.46±1.08 ml ) . Patients preferred Acapella in terms of usefulness of clearing secretions . Conclusion : The present study demonstrated increased sputum clearance following the use of the Acapella when compared to the threshold inspiratory muscle trainer . In addition , the Acapella was preferred by patients who judged that it was more useful in clearing secretions |
568 | 19,160,340 | Hepatic vascular occlusion does not decrease the blood transfusion requirements .
It decreases the cardiac output and increases the systemic vascular resistance .
In the comparison between continuous portal triad clamping and intermittent portal triad clamping , four of the five liver failures occurred in patients with chronic liver diseases undergoing the liver resections using continuous portal triad clamping .
There was no difference in any of the other important outcomes in any of the comparisons .
In elective liver resection , hepatic vascular occlusion can not be recommended over portal triad clamping .
Intermittent portal triad clamping seems to be better than continuous portal triad clamping at least in patients with chronic liver disease .
There is no evidence to support selective inflow occlusion over portal triad clamping .
The optimal method of intermittent portal triad clamping is not clear .
There is no evidence for any difference between the ischaemic preconditioning followed by vascular occlusion and intermittent vascular occlusion for liver resection in patients with non-cirrhotic livers . | BACKGROUND Vascular occlusion is used to reduce blood loss during liver resection surgery .
Various methods of vascular occlusion have been suggested .
OBJECTIVES To compare the benefits and harms of different methods of vascular occlusion during elective liver resection . | AIM To investigate the effect of low central venous pressure ( LCVP ) on blood loss during hepatectomy for hepatocellular carcinoma ( HCC ) . METHODS By the method of sealed envelope , 50 HCC patients were r and omized into LCVP group ( n=25 ) and control group ( n=25 ) . In LCVP group , CVP was maintained at 2 - 4 mmHg and systolic blood pressure ( SBP ) above 90 mmHg by manipulation of the patient 's posture and administration of drugs during hepatectomy , while in control group hepatectomy was performed routinely without lowering CVP . The patients ' preoperative conditions , volume of blood loss during hepatectomy , volume of blood transfusion , length of hospital stay , changes in hepatic and renal functions were compared between the two groups . RESULTS There were no significant differences in patients ' preoperative conditions , maximal tumor dimension , pattern of hepatectomy , duration of vascular occlusion , operation time , weight of resected liver tissues , incidence of post-operative complications , hepatic and renal functions between the two groups . LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group , being 903.9+/-180.8 mL vs 2 329.4+/-2 538.4 ( W=495.5 , P<0.01 ) and 672.4+/-429.9 mL vs 1 662.6+/-1 932.1 ( W=543.5 , P<0.01 ) . There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups . The length of hospital stay was significantly shortened in LCVP group as compared with the control group , being 16.3+/-6.8 d vs 21.5+/-8.6 d ( W=532.5 , P<0.05 ) . CONCLUSION LCVP is easily achievable in technique . Maintenance of CVP < or= 4 mmHg can help reduce blood loss during hepatectomy , shorten the length of hospital stay , and has no detrimental effects on hepatic or renal function Objective : To evaluate the protective effects of ischemic preconditioning in a prospect i ve r and omized study involving a large population of unselected patients and to identify factors affecting the protective effects . Summary Background Data : Ischemic preconditioning is an effective protective strategy in several animal models . Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion . Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown . Therefore , we conducted a prospect i ve r and omized study to evaluate the impact of ischemic preconditioning in liver surgery . Methods : A total of 100 unselected patients undergoing major liver resection ( > bisegmentectomy ) under inflow occlusion for at least 30 minutes were r and omized during surgery to either receive or not receive an ischemic preconditioning protocol ( 10 minutes of ischemia followed by 10 minutes of reperfusion ) . Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning . ATP contents in liver were measured as a possible mechanism of protection . Results : Both groups ( n = 50 in each ) were comparable regarding age , gender , duration of inflow occlusion , and resected liver volumes . Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients ( median peak AST 364 U/L vs. 520 U/L , P = 0.028 ; ALT 406 vs. 519 U/L , P = 0.049 ) . Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients , in patients with longer duration of inflow occlusion ( up to 60 minutes ) , and in cases of lower resected liver volume ( < 50 % ) . Patients with steatosis were also particularly protected by ischemic preconditioning . ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients . Conclusions : This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans . The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion , and in the presence of steatosis , and is possibly related to preservation of ATP content in liver tissue . Other strategies are needed in older patients Objective This prospect i ve r and omized study determined the influence of closed-suction drainage on the incidence of postoperative complications after elective hepatic resection . Summary Background Data Routine drainage is no longer advocated after several intra-abdominal surgical procedures . Methods A series of 81 patients who underwent elective hepatic resection were r and omly allocated to either a nondrainage group ( n = 39 ) and a drainage group with closed-suction drainage ( n = 42 ) . Indications for resection were 42 benign lesions and 39 malignant tumors , including 19 with cirrhosis . Major hepatic resection was performed in 25 patients and minor resection , in 56 . All patients underwent ultrasonography with puncture for bacteriologic cultures of all fluid collection s within the first 5 postoperative days . Results One patient died in each group . Ultrasonography found a significantly higher rate of subphrenic collection s in the drainage group compared with the nondrainage group ( respectively , 36 % vs. 15 % , p < 0.05 ) . These collection s were more frequently infected in the drainage group ( n = 6 ) than in the nondrainage group ( n = 2 ) . After major liver resection , the rate of intra-abdominal postoperative complications ( i.e. , subphrenic fluid collection s , hematomas , and bilomas ) was similar between the two groups . Conclusion Minor liver resection is safer without drainage . Major liver resection can be performed with or without abdominal drainage BACKGROUND Two r and omized prospect i ve studies suggested that ischemic preconditioning ( IP ) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad . The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow . STUDY DESIGN Sixty patients were r and omly divided into two groups : with ( n=30 ; preconditioning group ) and without ( n=30 ; control group ) IP ( 10 minutes of portal triad clamping and 10 minutes of reperfusion ) before major hepatectomy under vascular exclusion of the liver preserving the caval flow . Serum concentrations of aspartate transferase , alanine transferase , glutathione-S-transferase , and bilirubin and prothrombin time were regularly determined until discharge and at 1 month . Morbidity and mortality were determined in both groups . RESULTS Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP ( 851 + /- 1,733 IU/L and 427 + /- 166 IU/L respectively , p=0.2 ) . A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group . Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups . CONCLUSIONS IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow . This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates . The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended BACKGROUND AND AIMS Liver surgery usually involves ischemia and reperfusion ( I/R ) which results in oxidative stress and cell damage . The administration of antioxidants should diminish or prevent this damage . The purpose of this study was to investigate the effect of the antioxidant vitamin E on I/R injury . METHODS We carried out a placebo-controlled double-blind study on 68 patients undergoing elective , tumor-related , partial liver resection . 47 patients were qualified for the per protocol population based evaluation . The patients were r and omly assigned to two groups . The day before surgery one group received three infusions containing vitamin E ( 600 IU=540 mg vitamin E emulsion ) . The other group received three infusions of placebo . RESULTS Length of stay in the intensive care unit ( ICU ) was significantly shorter in the verum group than in the placebo group ( P<0.05 ) . There were signs of improvement for AUC AST ( P<0.05 ) , ALT and GLDH in the verum group after surgery . Serum vitamin E concentration increased after administration of vitamin E infusion and declined in both treatment groups after surgery ( P<0.01 ) . In the verum group vitamin E deficiency was prevented while vitamin E concentration remained low in the placebo group ( P<0.01 ) . CONCLUSIONS The findings from this study indicate that preoperative administration of vitamin E is safe and that this treatment may have beneficial effects by reducing the impact of I/R injury in liver surgery Hepatic pedicle clamping ( HPC ) is widely used to control intraoperative bleeding during hepatectomy ; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion . Recently , it has been shown that ischemic preconditioning ( IP ) reduces the ischemia-reperfusion damage for up to 30 minutes of continuous clamping in healthy liver . We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver su bmi tted to hepatectomy . IP was used in 21 patients ( group A ) ; mean + /- SD of liver ischemia was 54 + /- 19 minutes ( range , 27 - 110 ; in 7 cases > 60 minutes ) . In the other 21 patients , continuous clamping alone was used ( Group B ) ; liver ischemia lasted 36 + /- 14 minutes ( range , 13 - 70 ; in 2 cases > 60 minutes ) . Two patients in Group A ( 9.5 % ) and 3 in Group B ( 14.2 % ) received blood transfusions . In spite of the longer duration of ischemia ( P=.001 ) , patients with IP had lower aspartate aminotransferase ( AST ; P=.03 ) and alanine aminotransferase ( ALT ; P = not significant ) at postoperative day 1 , with a similar trend at postoperative day 3 . This was reconfirmed by multiple regression analysis , which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups , the increases were significantly smaller ( P<.001 ) with the use of preconditioning . In conclusion , the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia . This technique should be preferred to continuous clamping alone in healthy liver . Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping Background The success of hepatectomy can be associated with intraoperative blood loss because massive blood loss causes a poor prognosis . This study was design ed to evaluate the effect of infrahepatic inferior vena cava ( IVC ) clamping on the bleeding amount during hepatectomy . Methods Eighty-five patients scheduled to undergo hepatic resection were r and omly assigned to the IVC clamping or an IVC nonclamping group according to age , indocyanine green retention rate at 15 minutes , operative procedure , and number of tumors by prospect i ve , r and omized method . All analyses were compared by Mann-Whitney U test . Results Forty-three patients were assigned to the IVC clamping group and 42 to the nonclamping group ( IVC clamping group vs. non-clamping ) : total blood loss ( 499 vs. 584 ml ; p = 0.567 ) , amount of bleeding during hepatectomy ( 233 vs. 285 ml ; p = 0.474 ) , amount of bleeding during hepatectomy/area of dissection ( 4.9 vs. 6.6 ml/cm2 ; p = 0.63 ) , CVP difference ( −3 cmH2O vs. −1 cmH2O ; p < 0.01 ) , and diameter of the right hepatic vein ( −2.2 cm vs. 0 ; p < 0.01 ) . Conclusions Although we had speculated that infrahepatic IVC clamping would reduce blood loss during hepatectomy , we failed to demonstrate any beneficial effects in this clinical setting with low CVP OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Background / Aims : Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning ( IPC ) . Thus , we question ed in patients undergoing partial hepatectomy whether ( i ) IPC will increase plasma purine catabolites and whether ( ii ) formation of purines in response to vascular clamping ( Pringle maneuver ) can be attenuated by prior IPC . Methods : 75 patients were r and omly assigned to three groups : group I underwent hepatectomy without vascular clamping ; group II was subjected to the Pringle maneuver during resection , and group III was preconditioned ( 10 min ischemia and 10 min reperfusion ) prior to the Pringle maneuver for resection . Central , portal venous and arterial plasma concentrations of adenosine , inosine , hypoxanthine and xanthine were determined by high-performance liquid chromatography . Results : Duration of the Pringle maneuver did not differ between patients with or without IPC . Surgery without vascular clamping had only a minor effect on plasma purine concentrations . After IPC , plasma concentrations of purines transiently increased . After the Pringle maneuver alone , purine plasma concentrations were most increased . This strong rise in plasma purines caused by the Pringle maneuver , however , was significantly attenuated by IPC . When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine , the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning . Conclusion : These data demonstrate that ( i ) IPC increases formation of adenosine , and that ( ii ) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC . Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences , IPC might possibly decrease disturbances in the energy metabolism in the intestine as well BACKGROUND The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury , respectively , during liver surgery . In this prospect i ve clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning . METHODS Patients ( n=68 ) were assigned r and omly to three groups : ( i ) resection with the Pringle manoeuvre ; ( ii ) with ischaemic preconditioning before the Pringle manoeuvre for resection ; ( iii ) without pedicle clamping . RESULTS Following the Pringle manoeuvre the mean arterial pressure increased transiently , but significantly decreased after unclamping as a result of peripheral vasodilation . Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre . In addition , ischaemic preconditioning protected against reperfusion-induced tissue injury . CONCLUSIONS Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre OBJECTIVE To investigate the protective effect of ischemic preconditioning ( IPC ) for hepatic resection under hepatic blood inflow occlusion ( HBIO ) in hepatocellular carcinoma patients with cirrhosis and its possible mechanism . METHODS 29 consecutive patients resectable HCC were r and omized into two groups . IPC group : before HBIO , IPC with 5 min of ischemia and 5 min of reperfusion was given ; control group : simple HBIO . The liver function , hepatic caspase-3 activity , and apoptotic cell were compared between the two groups . RESULTS The AST , ALT levels of POD 1 , POD 3 and POD 7 in the IPC group were significantly higher than those of the control group , respectively ( t = 4.238 , P < 0.05 ) . The TBIL levels of POD 3 and POD 7 in the IPC group were significantly higher than those of the control group , respectively ( t = 2.296 , P < 0.05 ) . The ALB of POD 1 in the IPC group was higher than in the control group ( t = 2.029 , P > 0.05 ) . After 1 h of reperfusion , the hepatic caspase-3 activity and apoptotic sinusoidal endothelial cell were significantly higher than those of in the control group ( t = 2.349 , P < 0.05 ) . CONCLUSIONS IPC has the a protective effect in hepatic resection under HBIO in HCC patients with cirrhosis . Its mechanism is that sinusoidal endothelial cell apoptosis is inhibited by inhibiting caspase-3 activity HYPOTHESIS Blood loss in hepatic resection is an important determinant of operative outcome . OBJECTIVE To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection . DESIGN R and omized controlled trial . SETTING University hospital . PATIENTS Eighty patients scheduled to undergo hepatic resection were r and omly assigned to receive liver transection under normoventilation ( n = 40 ) or hypoventilation ( n = 40 ) . INTERVENTIONS During liver transection , in the normoventilation group , the tidal volume was 10 mL/kg and the respiratory rate was 10/min ; in the hypoventilation group , the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min . Liver transection was performed under total or selective inflow occlusion . MAIN OUTCOME MEASURE Blood loss . RESULTS Between the normoventilation and hypoventilation groups , no significant difference was found in total blood loss ( median [ range ] : 630 mL [ 72 - 3600 mL ] vs 630 mL [ 120 - 3520 mL ] ; P = .44 ) or blood loss per transection area ( median [ range ] : 7.3 mL/cm(2 ) [ 1.2 - 55.4 mL/cm(2 ) ] vs 9.8 mL/cm(2 ) [ 0.9 - 79.9 mL/cm(2 ) ] ; P = .55 ) . During liver transection , the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group ( median [ range ] : -0.7 cm H(2)O [ -3.0 to 1.8 cm H(2)O ] vs -0.2 cm H(2)O [ -4.0 to 2.0 cm H(2)O ] ; P = .007 ) . The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group ( maximum [ range ] : 50 mm Hg [ 28 - 66 mm Hg ] vs 37 mm Hg [ 27 - 60 mm Hg ] ; P<.001 ) . Transection time , postoperative liver function , hospitalization length , morbidity , and mortality were similar in the 2 groups . CONCLUSION This r and omized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection Objective : To evaluate whether ischemic preconditioning ( IP ) with continuous clamping or intermittent clamping ( IC ) of the portal triad confers better protection during liver surgery . Summary Background Data : IP and IC are distinct protective approaches against ischemic injury . Since both strategies proved to be superior in r and omized controlled trials ( RCTs ) to continuous inflow occlusion alone , we design ed a RCT to compare IP and IC in patients undergoing major liver resection . Methods : Noncirrhotic patients undergoing major liver resection were r and omized to receive IP with inflow occlusion ( n = 36 ) or IC ( n = 37 ) . Primary endpoints were postoperative liver injury and intraoperative blood loss . Postoperative liver injury was assessed by peak values of AST ( alanine aminotransferase ) and ALT ( aspartate aminotransferase ) , as well as the area under the curve ( AUC ) of the postoperative transaminase course . Secondary endpoints included resection time , the need of blood transfusion , ICU , and hospital stay as well as postoperative complications and mortality . Results : Both groups were comparable regarding demographics , ASA score , type of hepatectomy , duration of inflow occlusion ( range , 30–75 minutes ) , and resection surface . The transection-related blood loss was 146 versus 250 mL ( P = 0.008 ) , and when st and ardized to the resection surface 1.2 versus 1.8 mL/cm2 ( P = 0.01 ) for IP and IC , respectively . Although peak AST , AUCAST , and AUCALT were lower for IC , the differences did not reach statistical significance . Overall ( 42 % vs. 38 % ) and major ( 33 vs. 27 % ) postoperative complications as well as median ICU ( 1 vs. 1 day ) and hospital stay ( 10 vs. 11 days ) were similar between both groups . Conclusions : Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection . However , IP is associated with lower blood loss and shorter transection time . Therefore , both strategies can be recommended for noncirrhotic patients undergoing liver resection Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed OBJECTIVE To evaluate whether vascular inflow occlusion by the Pringle maneuver during hepatectomy can be safe and effective in reducing blood loss . SUMMARY BACKGROUND DATA Hepatectomy can be performed with a low mortality rate , but massive hemorrhage during surgery remains a potentially lethal problem . The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss , but there is a potential harmful effect on the metabolic function of hepatocytes . There has been no prospect i ve r and omized study to determine whether the Pringle maneuver can decrease blood loss during hepatectomy , improve outcome , or affect the metabolism of hepatocytes . METHODS From July 1995 to February 1997 , we studied 100 consecutive patients who underwent hepatectomy for liver tumors . The patients were r and omly assigned to liver transection under intermittent Pringle maneuver of 20 minutes and a 5-minute clamp-free interval ( n = 50 ) , or liver transection without the Pringle maneuver ( n = 50 ) . The surface area of liver transection was measured and blood loss during transection per square centimeter of transection area was calculated . Routine liver biochemistry , arterial ketone body ratio ( AKBR ) , and the indocyanine green ( ICG ) clearance test were done . RESULTS The two groups were comparable in terms of preoperative liver function and in the proportion of patients having major hepatectomy . The Pringle maneuver result ed in less blood loss per square centimeter of transection area ( 12 mL/cm2 vs. 22 mL/cm2 , p = 0.0001 ) , a shorter transection time per square centimeter of transection area ( 2 min/cm2 vs. 2.8 min/cm2 , p = 0.016 ) , a significantly higher AKBR in the first 2 hours after hepatectomy , lower serum bilirubin levels in the early postoperative period , and , in cirrhotic patients , higher serum transferrin levels on postoperative days 1 and 8 . The complication rate , the hospital mortality rate , and the ICG retention at 15 minutes on postoperative day 8 were equal for the two groups . CONCLUSION Performing the Pringle maneuver during liver transection result ed in less blood loss and better preservation of liver function in the early postoperative period . This is probably because there was less hemodynamic disturbance induced by the bleeding The effect of ischemic preconditioning ( IPC ) in orthotopic liver transplantation ( OLT ) has not yet been clarified . We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors r and omly assigned to receive ( IPC+ group , n = 23 ) or not ( IPC- group , n = 24 ) IPC ( 10-min ischemia + 15-min reperfusion ) . In 10 cases in the IPC+ group and in 12 in the IPC- group , the expression of inducible nitric oxide synthase ( iNOS ) , neutrophil infiltration , and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies . Median aspartate aminotransferase ( AST ) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 ( 398 vs. 1,234 U/L , P = 0.002 ; and 283 vs. 685 U/L , P = 0.009 ) . Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1 , 2 , and 3 ( 333 vs. 934 U/L , P = 0.016 ; 492 vs. 1,040 U/L , P = 0.008 ; and 386 vs. 735 U/L , P = 0.022 ) . Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks , incidence of graft nonfunction and graft and patient survival rates were similar between groups . Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups . iNOS was higher postreperfusion vs. prereperfusion in the IPC- group ( P = 0.008 ) . Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups ( IPC+ , P = 0.007 ; IPC- , P = 0.003 ) . Prereperfusion and postreperfusion apoptosis was minimal in both groups . In conclusion , IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis , but it showed no clinical benefits Background Hepatic veins remain patent during complete inflow occlusion ( CIO ) and bleeding from them may continue . Occlusion of the inferior vena cava ( ICV ) during CIO may reduce blood loss from hepatic veins . This study was design ed to compare the overall outcomes after application of CIO with or without occlusion of the ICV below the liver in complex mesohepatectomy for hepatocellular carcinoma ( HCC ) patients with cirrhosis . Material s and methods One hundred and eighteen ( 118 ) patients were r and omly assigned to CIO or a modified technique of hepatic vascular exclusion ( MTHVE ) . Hemodynamic parameters were evaluated and the amount of blood loss , measurement of liver enzymes , and postoperative progress were recorded . Results Blood loss during liver transection in CIO groups was significantly greater than that in MTHVE group ( P=0.046 ) . Thus , incidence of blood transfusion was significantly greater in patients of the CIO group ( P=0.041 ) . There were no significant differences in liver enzyme changes , bilirubin , or morbidity in the postoperative period between the two groups . Conclusions CIO with occlusion of the ICV below the liver is a safe , effective , and feasible technique during mesohepatectomy in HCC patients with cirrhosis . Excellent results were obtained with minimized bleeding , limited hepatic function damage , and low rate of postoperative complications OBJECTIVE The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping ( CPC ) or intermittent pedicular clamping ( IPC ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by pedicular clamping . There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma . METHODS Eighty-six patients undergoing liver resections were included in a prospect i ve r and omized study comparing the intra- and postoperative course under CPC ( n = 42 ) or IPC ( n = 44 ) with periods of 15 minutes of clamping and 5 minutes of unclamping . The data were further analyzed according to the presence ( steatosis > 20 % and chronic liver disease ) or absence of abnormal liver parenchyma . RESULTS The two groups of patients were similar in terms of age , sex , nature of the liver tumors , results of preoperative assessment , proportion of patients undergoing major or minor hepatectomy , and nature of nontumorous liver parenchyma . Intraoperative blood loss during liver transsection was significantly higher in the IPC group . In the CPC group , postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma . Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma , with two postoperative deaths . All of them were in the CPC group . CONCLUSIONS This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC , especially in patients with abnormal liver parenchyma 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 . BACKGROUND Experimental findings have demonstrated a beneficial role of retro grade blood flow from hepatic veins that takes place during the Pringle maneuver in liver resections . The cytoprotective effect of hepatovenous back-perfusion has not been evaluated in humans . A r and omized prospect i ve study was design ed to compare the response of liver cells to ischemic-reperfusion injury during the application of two different ischemic procedures : inflow versus inflow plus outflow vascular occlusion of the liver . STUDY DESIGN Forty patients were r and omly allocated to undergo liver resection using the continuous Pringle maneuver ( n = 20 ) or inflow plus outflow vascular occlusion of the liver by selective hepatic vascular exclusion ( n = 20 ) . Liver function was assessed on postoperative days 1 to 6 . Response of liver cells to I/R injury was evaluated by measuring interleukins IL-6 and IL-8 at 3 , 12 , 24 , and 48 hours after reperfusion . Oxidative stress was assessed by measuring malondialdehyde levels . RESULTS Both groups were comparable regarding ischemic time , operative time , and extent of liver resection . Patients in whom retro grade blood flow to the liver took place during the Pringle maneuver showed better liver function postoperatively and less severe hepatic I/R injuries compared with those undergoing liver resection using both inflow and outflow vascular occlusion . Oxidative stress was significantly lower in the Pringle maneuver group compared with the inflow plus outflow vascular occlusion group ( mean [ + /- SD ] malondialdehyde 8 + /- 2.1 micromol/L in the Pringle group versus 14.7 + /- 1.8 micromol/L in the selective hepatic vascular exclusion group 30 min after reperfusion , p < 0.01 ) . CONCLUSIONS Back perfusion via hepatic veins contributes to attenuation of I/R damage during the Pringle maneuver and should be preferred if possible during liver resection Objective A r and omized study was conducted of hilar dissection and the “ glissonean ” approach and stapling of the pedicle for major hepatectomies to contrast their feasibility , safety , amount of hemorrhage , postoperative complications , operative times , and costs . Summary Background Data The “ glissonean ” approach is reported as requiring a shorter portal triad closure time ; furthermore , the procedure seems to expedite the transection of the liver . Patients and Methods Between 1998 and 2001 , 80 patients were enrolled in this study . The major liver resections included 15 extended right , 7 extended left , 42 right , and 16 left hepatectomies . The patients were r and omly assigned to the hilar dissection group ( G1 ; n = 40 ) or to the “ glissonean ” approach and stapling of the portal triad group ( G2 ; n = 40 ) . Results The groups were equally matched for age , sex , diagnosis , mean resected specimen weight , number of tumoral lesions , type of liver resection performed , and percentage of patients with margin invasion ( G1 : 4 ; 10 % vs G2 : 5 ; 12.5 % ) . The duration of the 2 procedures was similar ( G1 : 247 ± 54 min vs G2 : 236 ± 43 min ; P = 0.4 ) . However , the duration of the hilar dissection was shorter for G2 ( 50 ± 17 min ) versus G1 ( 70 ± 26 min ; P < 0.001 ) . By contrast , the duration of pedicular clamping was shorter for G1 ( 43 ± 15 min ) versus G2 ( 51 ± 15 min ; P = 0.015 ) . No differences were observed in the amount of hemorrhage ( G1 : 887 ± 510 mL vs G2 : 937 ± 636 mL ; P = 0.7 ) , and only 6 patients in G1 and 10 in G2 were transfused ( P = 0.26 ) . Morbidity rates were similar for both groups ( G1 : 23 % vs G2 : 33 % ; P = 0.3 ) . Surgical injury of the contralateral biliary duct was not observed . However , 3 patients in G1 and 4 patients in G2 presented a biliary fistula that resolved spontaneously . Postoperative hospital stay was similar ( G1 : 8 [ range , 6 - 24 ] vs G2 : 9 [ range , 5 - 31 ] days ; P = 0.6 ) . The postoperative levels of alanine transaminase ( ALT ) during the 2 first postoperative days were lower for G1 than G2 . Cost of the surgical material was 1235.80 US for G1 and 1301.10 US for G2 . Conclusions The 2 techniques are equally effective procedures for treating hilar structures . Although en bloc stapling transection is faster , hilar dissection was associated with a shorter pedicular clamping time , less cytolysis , and the material s required were less expensive The optimal ischaemic interval during hepatectomy with intermittent pedicle occlusion ( IPO ) remains to be established . The aim of the present r and omized clinical trial was to compare the short‐term outcome of hepatectomy using IPO with an ischaemic interval of 15 versus 30 min BACKGROUND Intermittent Pringle manoeuvre result ed in less blood loss and better preservation of liver function when it was applied for fewer than 120 minutes . The mechanism of better preservation of liver function under intermittent Pringle manoeuvre at molecular level remains unclear . Furthermore , the ultrastructural features in the liver with chronic diseases under intermittent Pringle manoeuvre have not been studied . The aim of the study is to investigate the expression of stress genes and ultrastructural change of the liver under intermittent Pringle manoeuvre . METHODS From July 1995 to February 1998 , 131 patients underwent hepatectomy for liver tumours ( 61 patients without Pringle manoeuvre and 70 patients with intermittent Pringle manoeuvre ) . Twenty-five patients ( 15 with Pringle manoeuvre and 10 without Pringle manoeuvre ) were included in the study of hepatic stress gene expression during hepatectomy . Twenty-two patients ( 18 patients with intermittent Pringle manoeuvre and four patients without Pringle manoeuvre ) were r and omly assigned for electron microscopic examination . RESULTS For the expression of stress genes , both the heat shock genes ( HSP 70A and HSC 70 ) and acute phase genes ( TNF-alpha and interleukin-6 ) were detected simultaneously in the patients with or without intermittent Pringle manoeuvre . The patients under intermittent Pringle manoeuvre had relatively higher mRNA levels of heat shock gene 70 family , which is related to intracellular repair and protection . Induction of TNF-alpha and interleukin-6 genes , which contributed to ischaemia-reperfusion injury and postoperative complication , was not found in the patients under intermittent Pringle manoeuvre . Under the electron microscopy , the hepatic ultrastructure was well maintained under intermittent Pringle manoeuvre whatever the liver status , even when the accumulated ischaemic duration was extended to 120 min . CONCLUSION Intermittent Pringle manoeuvre induced relatively higher expression of heat shock genes , which are related to intracellular homeostasis , and is consistent with the well maintenance of liver ultrastructure BACKGROUND / AIMS Many experimental studies on ischemia-reperfusion injury in animals suggest a preventive effect of antioxidants , but the clinical significance of these findings is still unclear . The aim of our study was to evaluate the effect of antioxidant treatment with vitamins on liver function parameters during liver resection . METHODOLOGY Our prospect i ve r and omized study comprised 58 patients undergoing major liver surgery , including the Pringle maneuver . In the treatment group 32 patients received a multivitamin infusion ( Omnibionta ) which included 10 mg of alpha-tocopherol acetate , 2 mg of DL-alpha-tocopherol and 1 g of ascorbate . The control group consisted of 26 patients . Various parameters associated with liver function , such as transaminases , lactate , ammonia , bilirubin , cholinesterase and clotting parameters were measured preoperatively , at the beginning of liver ischemia , 15 , 30 and 60 minutes after reperfusion onset and every 12 hours after the operation . RESULTS The Mann-Whitney-Wilcoxon-Test showed statistically significant differences in the postischemic changes between the treatment group and the control group for the Quick test ( prothrombin time ) : p = 0.01 . The transaminases were also markedly better in the treatment group ( splitting-up slightly more delayed than with the Quick test ) . A smaller effect was seen with cholinesterase . Lactate , however , increased intraoperatively with a strong correlation to the duration of ischemia and returned quickly to baseline values without any remarkable influence of the antioxidant treatment . CONCLUSION In our study , antioxidant treatment with a multivitamin infusion showed a positive effect on postischemic liver function parameters BACKGROUND The aim of this study was to compare ischemic preconditioning with the intermittent vascular occlusion technique in liver resections performed under inflow and outflow occlusion . METHODS Fifty-four patients with resectable liver tumors assigned were r and omly to undergo surgery with either ischemic preconditioning ( IP group , n = 27 ) or with intermittent vascular occlusion ( IVO group , n = 27 ) . Both groups were compared regarding surgical parameters , aspartate transaminase levels , and apoptosis . RESULTS For warm ischemic time less than 40 minutes , no significant difference was noticed between the 2 groups apart from caspase-3 activity , which was higher in the IVO group than in the IP group ( 17.2 + /- 3.4 vs. 10.3 + /- 5.2 , P < .05 ) . When warm ischemia exceeded 40 minutes , the IP group showed higher levels in blood aspartate transaminase levels on day 3 ( 442 + /- 178 IU/L vs. 305 + /- 104 IU/L , P < .05 ) and higher caspase-3 levels ( 26.5 + /- 5.7 count/high-power field [ hpf ] vs. 20.7 + /- 3.6 count/hpf , P < .05 ) and apoptotic activity ( 28.5 + /- 7.5 count/hpf vs. 20.2 + /- 4.1 count/hpf , P < .05 ) , as compared with the IVO group . CONCLUSIONS Although both techniques showed comparable efficacy for short ischemic times , intermittent vascular occlusion provided better cytoprotection when ischemia exceeded 40 minutes OBJECTIVE The authors compared operative course of patients undergoing major liver resections under portal triad clamping ( PTC ) or under hepatic vascular exclusion ( HVE ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by PTC or HVE . Specific complications and postoperative hepatocellular injury mediated with two procedures have not been compared . METHODS Fifty-two noncirrhotic patients undergoing major liver resections were included in a prospect i ve r and omized study comparing both the intraoperative and postoperative courses under PTC ( n = 24 ) or under HVE ( n = 28 ) . RESULTS The two groups were similar at entry , but eight patients were crossed over to the other group during resection . In the HVE group , hemodynamic intolerance occurred in four ( 14 % ) patients . In the PTC group , pedicular clamping was not efficient in four patients , including three with involvement of the cavohepatic intersection and one with persistent bleeding due to tricuspid insufficiency . Intraoperative blood losses and postoperative enzyme level reflecting hepatocellular injury were similar in the two groups . Mean operative duration and mean clampage duration were significantly increased after HVE . Postoperative abdominal collection s and pulmonary complications were 2.5-fold higher after HVE but without statistical significance , whereas the mean length of postoperative hospital stay was longer after HVE . CONCLUSIONS This study shows that both methods of vascular occlusion are equally effective in reducing blood loss in major liver resections . The HVE is associated with unpredictable hemodynamic intolerance , increased postoperative complications with a longer hospital stay , and should be restricted to lesions involving the cavo-hepatic intersection AIM To investigate the protective effect of ischemic preconditioning ( IPC ) on hepatocellular carcinoma ( HCC ) patients with cirrhosis undergoing hepatic resection under hepatic inflow occlusion ( HIO ) and its possible mechanism . METHODS Twenty-nine consecutive patients with resectable 0HCC were r and omized into two groups : IPC group : before HIO , IPC with 5 min of ischemia and 5 min of reperfusion was given ; control group : no IPC was given . Liver functions , hepatic Caspase-3 activity , and apoptotic cells were compared between these two groups . RESULTS On postoperative days ( POD ) 1 , 3 and 7 , the aspartate transaminase ( AST ) and alanine transaminase ( ALT ) levels in the IPC group were significantly lower than those in the control group ( P<0.05 ) . On POD 3 and 7 , the total bilirubin level in the IPC group was significantly lower than that in the control group ( P<0.05 ) . On POD 1 , the albumin level in the IPC group was higher than that in the control group ( P = 0.053 ) . After 1 h of reperfusion , both hepatic Caspase-3 activity and apoptotic sinusoidal endothelial cells in the IPC group were significantly lower than those in the control group ( P<0.05 ) . CONCLUSION IPC has a potential protective effect on HCC patients with cirrhosis . Its protective mechanism underlying the suppression of sinusoidal endothelial cell apoptosis is achieved by inhibiting Caspase-3 activity BACKGROUND The optimal duration of hepatic vascular inflow occlusion ( Pringle maneuver ) and reperfusion during liver resection are not defined . The aim of this study was to describe the changes that occur in liver tissue pH , partial pressure of carbon dioxide ( P(L)CO(2 ) ) , and partial pressure of oxygen ( P(L)O(2 ) ) and by using the P(L)CO(2 ) as a predictor of hepatocellular damage define the optimal clamp/release regime for intermittent portal clamping during liver resection . METHODS Continuous pH , P(L)CO(2 ) , and P(L)O(2 ) measurements were obtained using a Paratrend multi-parameter sensor ( Diametrics Medical Inc. , Roseville , MN ) in 13 patients undergoing elective partial liver resection . Patients were r and omly allocated to undergo a 10-min clamp/5-min release regime ( group 1 ) or a 20-min clamp/10-min release regime ( group 2 ) . RESULTS In group 1 ( n = 6 ) P(L)CO(2 ) increased and pH decreased significantly after 10 min of clamping and returned to baseline within 5 min of reperfusion . In group 2 ( n = 7 ) the P(L)CO(2 ) increased and pH decreased significantly after 10 min of clamping , with a further significant change after 20 min . Following 10 min of reperfusion , pH and P(L)CO(2 ) had not returned to baseline . P(L)O(2 ) did not change significantly with either intermittent portal clamping regime . CONCLUSIONS A reperfusion of 5 min is sufficient to restore the P(L)CO(2 ) and liver tissue pH to normal after 10 min of clamping , but more than 10 min of reperfusion is required after 20 min of clamping . To minimize hepatic ischemia during liver resection , a 10-min clamp/5-min release regime should be used HYPOTHESES Temporary vascular clampage ( Pringle maneuver ) during liver surgery can cause ischemia-reperfusion injury . In this process , activation of polymorphonuclear leukocytes ( PMNLs ) might play a major role . Thus , we investigated the effects of hepatic ischemic preconditioning on PMNL functions . DESIGN Prospect i ve r and omized study . Patients who underwent partial liver resection were r and omly assigned to 3 groups : group 1 without Pringle maneuver ; group 2 with Pringle maneuver , and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection . SETTING University hospital , Munich , Germany . PATIENTS Seventy-five patients underwent hepatic surgery mostly owing to metastasis . MAIN OUTCOME MEASURES Perioperative factors for PMNL activation , inflammation , and postoperative hepatocellular integrity . RESULTS Ischemia-reperfusion of the human liver ( mean + /- SD time to perform the Pringle maneuver , 35.5 + /- 2.6 minutes ) caused ( 1 ) a decrease in the number of circulating PMNLs , ( 2 ) their intrahepatic sequestration , ( 3 ) their systemic activation , and ( 4 ) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels . In parallel , cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced . When ischemic preconditioning preceded the Pringle maneuver , activation of PMNLs and cytokine plasma levels was reduced as evidence d by the attenuation of superoxide anion production , beta(2)-integrin up-regulation , and interleukin 8 serum concentrations , followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days . CONCLUSIONS These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver . The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning OBJECTIVE To assess the preventive effect of simple in situ cooling on ischaemic injury in human livers . DESIGN R and omised study . SETTING University department of surgery , Japan . SUBJECTS 20 patients who were to undergo liver resection ( right lobectomy , n = 6 , left lobectomy , n = 3 , and posterior segmentectomy , n = 1 , in each group ) ; all but 2 who had normal remnant livers and were r and omised to undergo either warm ischaemia or in situ cooling ( n = 10 in each group ) . INTERVENTIONS Hypothermia was induced by rapid infusion of roughly 450 ml of cold Ringer 's lactate into the portal vein during occlusion of the portal triad before resection . MAIN OUTCOME MEASURES Occlusion time , ATP concentrations , biochemical indicators of liver damage , and coagulation profile . RESULTS The mean ( SD ) occlusion time was 55 ( 6 ) minutes for the warm ischaemia group and 53 ( 3 ) for the in situ cooling group . After in situ cooling the state of the liver as indicated by serum alanine aminotransferase activity ( ALT ) and prothrombin time had improved substantially . Mean ( SD ) ALT activity was 516 ( 168 ) U/I in the warm ischaemia group compared with 305 ( 154 ) in the in situ cooling group ( p < 0.02 ) on the first postoperative day . The respective figures for prothrombin time ( % ) were 56 ( 23 ) compared with 77 ( 14 ) , ( p < 0.05 ) . CONCLUSION In situ cooling lessened the amount of ischaemic damage done to the liver during hepatectomy compared with treatment with warm ischaemia BACKGROUND Intermittent occlusion of hepatic blood inflow by means of a hemihepatic or total hepatic occlusion technique is essential for reducing operative blood loss . Central liver resection to preserve more functioning liver parenchyma is m and atory for central ly located liver tumors in patients with cirrhosis , but it requires a longer overall hepatic ischemic time because of a wide transection plane . No controlled comparison has been performed for the 2 techniques in these operations . HYPOTHESIS Hemihepatic inflow occlusion may be beneficial in cirrhotic patients who undergo complex central hepatectomy with a wide liver transection plane . DESIGN A prospect i ve , r and omized study . SETTING University hospital and tertiary referral center . PATIENTS During liver parenchymal transection , 58 cirrhotic patients who underwent complex central liver resections with a wide transection plane were prospect ively r and omized into 2 groups . In the group undergoing total hepatic inflow clamping ( group T ; n = 28 ) , occlusion of hepatic blood inflow was performed for 15 minutes with declamping for 5 minutes . In the group undergoing selective clamping of ipsilateral blood inflow ( group H ; n = 30 ) , clamping was performed for 30 minutes with declamping for 5 minutes . INTERVENTION Comparison of patient background s , operative procedures , and early postoperative results . MAIN OUTCOME MEASURES Operative blood loss , need for blood transfusion , and postoperative morbidity . RESULTS The patients ' background s , operative procedures , and area of liver transection plane were not significantly different between the 2 groups . In all patients , the liver transection areas were greater than 60 cm(2 ) and overall liver ischemic times were greater than 60 minutes . The amount of operative blood loss and incidence of blood transfusion were significantly greater in group T because of greater blood loss during declamping . Overall liver ischemic and total operative times , postoperative morbidity , and postoperative changes in liver enzyme levels were not significantly different between groups . No in-hospital deaths occurred in either group . CONCLUSIONS Intermittent hemihepatic and total occlusion of hepatic blood inflow are safe in cirrhotic patients with an overall ischemic time of greater than 60 minutes . However , for complex liver resections with an estimated liver transection plane of greater than 60 cm(2 ) , hemihepatic occlusion of blood inflow , if feasible , may be recommended in cirrhotic patients to reduce operative blood loss and the incidence of blood transfusion under our defined occlusion time BACKGROUND / AIMS It has been shown that hepatic pedicle clamping is a safe and effective technique to control bleeding during liver resection . A major drawback can be the induction of liver ischemia and splanchnic venous stasis . METHODOLOGY This r and omized controlled clinical trial compared continuous and intermittent hepatic pedicle clamping during resection of the cirrhotic liver in order to determine which technique is more effective in reducing operative blood loss and producing less ischemic injury . In 18 patients we performed continuous portal triad clamping during liver transection while in 17 patients we performed intermittent clamping . The two groups matched for extent of resection . Serial hepatic function tests were performed on postoperative day 1 , 3 and 7 . RESULTS No significant difference was found between the two groups in terms of operative findings . Operative mortality was 5.7 % ( 2 patients ) . Six patients ( 17.3 % ) had postoperative complications . There were no significant differences between the two groups with regard to postoperative liver function tests and coagulation profile . CONCLUSIONS Continuous and intermittent clamping are both effective in reducing blood loss during hepatectomy in cirrhosis . The two techniques seem to be comparable in terms of ischemic injury . Our findings suggest that intermittent portal triad clamping may not be necessary . As this is contrary to the normal expectancy , additional studies may be needed The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min . The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre BACKGROUND Total hepatic vascular exclusion ( THVE ) and selective hepatic vascular exclusion ( SHVE ) are two effective techniques for bleeding control in major hepatic resections . Outcomes of the two procedures were compared . METHODS Patients undergoing major liver resection were r and omly allocated to the THVE and SHVE groups . Intraoperative hemodynamic changes and the postoperative course of the two groups were compared . RESULTS During vascular clamping , the THVE group showed a significant elevation in pulmonary vascular resistance , systemic vascular resistance , intrapulmonary shunts , and a significant reduction in cardiac index , compared with the SHVE group ( P < 0.05 ) . Patients undergoing THVE received more crystalloids and blood , showed more severe liver , renal and pancreatic dysfunction , and had a longer hospital stay than the SHVE group ( P < 0.05 ) . CONCLUSIONS Both techniques are equally effective in bleeding control in major liver resections . THVE is associated with cardiorespiratory and hemodynamic alterations and may be not tolerated by some patients . SHVE is well tolerated with fewer postoperative complications and shorter hospitalization time Selective hepatic vascular exclusion ( SHVE ) and the Pringle maneuver are two methods used to control bleeding during hepatectomy . They are compared in a prospect i ve r and omized study , where 110 patients undergoing major liver resection were r and omly allocated to the SHVE group or the Pringle group . Data regarding the intraoperative and postoperative courses of the patients are analyzed . Intraoperative blood loss and transfusion requirements were significantly decreased in the SHVE group , and postoperative liver function was better in that group . Although there was no difference between the two groups regarding the postoperative complications rate , patients offered the Pringle maneuver had a significantly longer hospital stay . The application of SHVE did not prolong the warm ischemia time or the total operating time . It is evident from the present study that SHVE performed by experienced surgeons is as safe as the Pringle maneuver and is well tolerated by the patients . It is much more effective than the Pringle maneuver for controlling intraoperative bleeding , and it is associated with better postoperative liver function and shorter hospital stay Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes ( PMN ) may play a critical role in ischemia‐ reperfusion injury . To evaluate whether similar mechanisms are operative in human liver , six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were r and omized for utilization of hepatic vascular exclusion ( HVE ) as a model of ischemia‐reperfusion injury . Portal and systemic levels of acute reactant cytokines ( interleukin 6 [ IL‐6 ] , interleukin 1 [ IL‐1 ] , tumor necrosis factor α [ TNF‐α ] ) and neutrophil adhesion in serial liver biopsy specimens were studied . Correlations among mediators , leukocyte adhesion , and markers of liver injury were also evaluated . Hepatic vascular exclusion result ed in substantial and reproducible changes in portal and arterial IL‐6 levels in both cirrhotic and noncirrhotic patients . Portal and systemic cytokine levels were comparable in most instances , whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients . Negative correlations were found between IL‐6 levels at the time of reperfusion and later TNF‐α levels . IL‐6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications . Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients . In cirrhotic patients , the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury . This study in humans shows that acute reactant cytokines are released during liver ischemia and , interestingly , that IL‐6 levels strongly correlate with clinical and laboratory measures of injury . Further studies to evaluate possible causal relationship with hepatic injury are warranted , with emphasis on the role of IL‐6 and PMN adhesion |
569 | 29,023,837 | All this is driven by the salience of international metrics of attainment as used , for example , by the Program for International Student Assessment .10,11 The decline of PSHE is of particular concern because there is strong evidence from systematic review s that school curriculum-based health education is one key element in strategies to reduce outcomes such as alcohol consumption,12 smoking,13 drug | Public education systems throughout Europe and North America are subjecting students to more ‘ ‘ high-stakes ’ ’ testing , with governments using the result ing data to manage schools ’ performance and help parents choose schools . | OBJECTIVE To report experimental impacts of a universal , integrated school-based intervention in social-emotional learning and literacy development on change over 1 school year in 3rd- grade children 's social-emotional , behavioral , and academic outcomes . METHOD This study employed a school-r and omized , experimental design and included 942 3rd- grade children ( 49 % boys ; 45.6 % Hispanic/Latino , 41.1 % Black/African American , 4.7 % non-Hispanic White , and 8.6 % other racial/ethnic groups , including Asian , Pacific Isl and er , Native American ) in 18 New York City public elementary schools . Data on children 's social-cognitive processes ( e.g. , hostile attribution biases ) , behavioral symptomatology ( e.g. , conduct problems ) , and literacy skills and academic achievement ( e.g. , reading achievement ) were collected in the fall and spring of 1 school year . RESULTS There were main effects of the 4Rs Program after 1 year on only 2 of the 13 outcomes examined . These include children 's self-reports of hostile attributional biases ( Cohen 's d = 0.20 ) and depression ( d = 0.24 ) . As expected based on program and developmental theory , there were impacts of the intervention for those children identified by teachers at baseline with the highest levels of aggression ( d = 0.32 - 0.59 ) on 4 other outcomes : children 's self-reports of aggressive fantasies , teacher reports of academic skills , reading achievement scaled scores , and children 's attendance . CONCLUSIONS This report of effects of the 4Rs intervention on individual children across domains of functioning after 1 school year represents an important first step in establishing a better underst and ing of what is achievable by a schoolwide intervention such as the 4Rs in its earliest stages of unfolding . The first-year impacts , combined with our knowledge of sustained and exp and ed effects after a second year , provide evidence that this intervention may be initiating positive developmental cascades both in the general population of students and among those at highest behavioral risk . ( PsycINFO Data base Record ( c ) 2010 APA , all rights reserved ) The Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research BACKGROUND We examined the differential impact of a well-established human immunodeficiency virus (HIV)/sexually transmitted infections ( STIs ) curriculum , Be Proud ! Be Responsible ! , when taught by school nurses and health education classroom teachers within a high school curricula . METHODS Group-r and omized intervention study of 1357 ninth and tenth grade students in 10 schools . Twenty-seven facilitators ( 6 nurses , 21 teachers ) provided programming ; nurse-led classrooms were r and omly assigned . RESULTS Students taught by teachers were more likely to report their instructor to be prepared , comfortable with the material , and challenged them to think about their health than students taught by a school nurse . Both groups reported significant improvements in HIV/STI/condom knowledge immediately following the intervention , compared to controls . Yet , those taught by school nurses reported significant and sustained changes ( up to 12 months after intervention ) in attitudes , beliefs , and efficacy , whereas those taught by health education teachers reported far fewer changes , with sustained improvement in condom knowledge only . CONCLUSIONS Both classroom teachers and school nurses are effective in conveying reproductive health information to high school students ; however , teaching the technical ( eg , condom use ) and interpersonal ( eg , negotiation ) skills needed to reduce high-risk sexual behavior may require a unique set of skills and experiences that health education teachers may not typically have OBJECTIVES We sought to test the efficacy of an intervention that was design ed to promote social inclusion and commitment to education , in reducing among students health risk behaviors and improving emotional well-being . METHODS The design was a cluster-r and omized trial in 25 secondary schools in Victoria , Australia . The subjects were 8th- grade students ( aged 13 to 14 y ) in 1997 ( n=2545 ) and subsequent 8th- grade students in 1999 ( n=2586 ) and 2001 ( n=2463 ) . The main outcomes were recent substance use , antisocial behavior , initiation of sexual intercourse , and depressive symptoms . RESULTS At 4-year follow-up , the prevalence of marked health risk behaviors was approximately 20 % in schools in the comparison group and 15 % in schools in the intervention group , an overall reduction of 25 % . In ordinal logistic regression models a protective effect of intervention was found for a composite measure of health risk behaviors in unadjusted models ( odds ratio [OR]= 0.69 ; 95 % confidence interval [CI]= 0.50 , 0.95 ) and adjusted models ( OR= 0.71 ; CI = 0.52 , 0.97 ) for potential confounders . There was no evidence of a reduction in depressive symptoms . CONCLUSION The study provides support for prevention strategies in schools that move beyond health education to promoting positive social environments Summary of Etiological Analyses . T his analysis confirm ed the i m portance of school bonding to child devel-opm ent . V arious techniques w ere used to exam ine the rela-tionship betw een school bonding and positive and problembehavior , and these relationships w ere found during child-h o o d and ad o lescen ce . S chool b o n d in g in elem en taryschool w as related to initiation of drinking , sm oking , and alcohol abuse and dependence at age 2 1 . It also related tolow er likelihood of becom ing serious offenders in m iddleschool and joining a gang in adolescence . E lem entary and m iddle school bonding had a negative effect on violence inm iddle school through age 2 1 . It also reduced the chance ofschool m isbehavior , grade repetition , and dropout . S choolbonding also affected positive developm ent . S chool bond-ing w as associated w ith increases in academ ic achievem ent and social skills . S chool bonding effects extended to high -risk groups including aggressive boys , children w ith parent sw ho m odeled problem behaviors , and children from low -incom e fam ilies . S chool bonding in m iddle school w asrelated to desistance of serious delinquent behavior . T herelationship w as m aintained through age 2 1 , w ith studentsreporting greater school bonding in sevent h grade m orelikely to desist rather than escalate the seriousness of theiroffending . S chool bonding in m iddle school and the patternof bonding throughout m iddle and high school also relatedto reduced levels of substance use in 12th grade . T h u s , school bonding during elem entary and m iddle school w asconsistently related negatively to problem behaviors in thislongitudinal study .S everal com peting factors that m ight explain the rela-tionship betw een school bonding and problem behaviorsw ere controlle d in the analyses , lending credibilit y to thepotential causal effect of school bonding . H ow ever , w hilenonexperim ental , longitudinal studies establish tim e order , they do not establish cause . A stronger criterion for estab-lishing the causal effect of school bonding com es fromintervention studies aim ed at changing the levels of schoolbonding and exam ining the effects on positive and problembehavior . S tatistically significant results of the preventionexperim ent em bedded w ithin S S D P are described below This study contributes to ongoing scholarship at the nexus of translational research , education reform , and the developmental and prevention sciences . It reports 2-year experimental impacts of a universal , integrated school-based intervention in social-emotional learning and literacy development on children 's social-emotional , behavioral , and academic functioning . The study employed a school-r and omized , experimental design with 1,184 children in 18 elementary schools . Children in the intervention schools showed improvements across several domains : self-reports of hostile attributional bias , aggressive interpersonal negotiation strategies , and depression , and teacher reports of attention skills , and aggressive and socially competent behavior . In addition , there were effects of the intervention on children 's math and reading achievement for those identified by teachers at baseline at highest behavioral risk . These findings are interpreted in light of developmental cascades theory and lend support to the value of universal , integrated interventions in the elementary school period for promoting children 's social-emotional and academic skills |
570 | 32,059,593 | The most frequently assessed illnesses were neoplasms while the most evaluated interventions were pharmacological .
The main source of costs and effects of RWD were information systems . | Economic evaluations using Real World Data ( RWD ) has been increasing in the very recent years , however , this source of information has several advantages and limitations .
The aim of this review was to assess the quality of full economic evaluations ( EE ) developed using RWD . | PURPOSE The purpose of this study was to determine the cost-effectiveness of knee arthroscopy and anterior cruciate ligament ( ACL ) reconstruction . METHODS Retrospective analysis of prospect ively collected data from a single-surgeon , institutional review board-approved outcomes registry included 2 cohorts : surgically treated knee arthroscopy and ACL reconstruction patients . Our outcome measure is cost-effectiveness ( cost of a quality -adjusted life-year [ QALY ] ) . The QALY is calculated by multiplying difference in health-related quality of life , before and after treatment , by life expectancy . Health-related quality of life is measured by use of the Quality of Well-Being scale , which has been vali date d for cost-effectiveness analysis . Costs are facility charges per the facility cost-to-charges ratio plus surgeon fee . Sensitivity analyses are performed to determine the effect of variations in costs or outcomes . RESULTS There were 93 knee arthroscopy and 35 ACL reconstruction patients included at a mean follow-up of 2.1 years . Cost per QALY was $ 5,783 for arthroscopy and $ 10,326 for ACL reconstruction ( 2009 US dollars ) . Sensitivity analysis shows that our results are robust ( relatively insensitive ) to variations in costs or outcomes . CONCLUSIONS Knee arthroscopy and knee ACL reconstruction are very cost-effective 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 and Purpose — There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants ( NOACs ) and warfarin in Asians with nonvalvular atrial fibrillation . We aim ed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population , with particular focus on high-risk patients . Methods — Using the Korean National Health Insurance Service data base , we analyzed the risk of ischemic stroke , intracranial hemorrhage ( ICH ) events , and all-cause death in NOAC users ( n=11 611 total , n=5681 taking rivaroxaban , n=3741 taking dabigatran , and n=2189 taking apixaban ) compared with propensity score-matched warfarin users ( n=23 222 ) among patients with high-risk atrial fibrillation ( CHA2DS2-VASc score ≥2 ) between 2014 and 2015 . Results — NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin . All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin . Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome ( ischemic stroke , ICH , and all-cause death ) compared with warfarin , whereas this was nonsignificant for rivaroxaban . Among previously oral anticoagulant – naive patients ( n=23 262 ) , dabigatran and apixaban were superior to warfarin for ICH prevention , whereas rivaroxaban and warfarin were associated with similar risk of ICH . Conclusions — In real-world practice among a high-risk Asian atrial fibrillation population , all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin . All-cause mortality was significantly lower only with dabigatran and apixaban OBJECTIVES Heart transplantation ( HT ) and ventricular assist devices ( VAD ) for the management of end-stage heart failure have not been directly compared . We compare the outcomes and use of re sources with these 2 strategies in 2 European countries with different allocation systems . METHODS We studied 83 patients managed by VAD as the first option in Bad Oeynhausen , Germany ( Group I ) and 141 managed with either HT or medical therapy , as the first option , in Paris , France ( Group II ) . The primary end-point was 2-year survival . Kaplan-Meier analyses were performed after the application of propensity score weights to mitigate the effects of non-r and om group assignment . The secondary end-points were re source utilization and costs . Subgroup analyses were performed for patients undergoing HT and patients treated with inotropes at the enrolment time . RESULTS The Group I patients were more severely ill and haemodynamically compromised , and 28 % subsequently underwent HT vs 55 % primary HT in Group II , P < 0.001 . The adjusted probability of survival was 44 % in Group I vs 70 % in Group II , P < 0.0001 . The mean cumulated 2-year costs were € 281 361 ± 156 223 in Group I and € 47 638 ± 35 061 in Group II , P < 0.0001 . Among patients who underwent HT , the adjusted probability of survival in Group I ( n = 23 ) versus Group II ( n = 78 ) was 76 % versus 68 % , respectively ( 0.09 ) , though it differed in the inotrope-treated subgroups ( 77 % in Group I vs 67 % in Group II , P = 0.04 ) . CONCLUSIONS HT should remain the first option for end-stage heart failure patients , associated with improved outcomes and better cost-effectiveness profile . VAD devices represent an option when transplant is not possible or when patient presentation is not optimal Background Surgical site infections ( SSIs ) lead to increased patient morbidity and healthcare costs . Our objective was to decrease the SSI rate following gynecologic surgery . Methods Adult patients undergoing abdominal surgery for gynecologic malignancy or benign disease received the following : patient education ; preoperative antibacterial soap ; appropriate antibiotic prophylaxis ; change of gloves and use of clean instruments at surgical closure ; surgical dressing for 48 h ; and a post-discharge phone call . The baseline SSI rate was determined retrospectively ( 1 April 2014–30 June 2014 ) , while the post-intervention SSI rate was determined prospect ively ( 16 February 2015–15 October 2015 ) . The main outcome was the overall SSI rate with secondary outcomes , including the rate of superficial , deep , incisional and organ space infection , as well as the cost effectiveness of the bundle . Results A total of 232 baseline and 555 post-intervention patients were included in the study . No differences were observed between the baseline and post-intervention groups with regard to median body mass index ( BMI ) , surgical approach , receipt of preoperative chemotherapy and /or radiation therapy , and cases including bowel surgery . Overall , the SSI rate decreased significantly from baseline [ 12.5 % ] to post-intervention [ 7.4 % ] ( odds ratio [ OR ] 0.56 , 90 % confidence interval [ CI ] 0.37–0.85 ; p = 0.01 ) . A 40 % decrease was noted in the rate of superficial and deep infections ( 9.5 vs. 5.9 % ; OR 0.60 , 90 % CI 0.38–0.97 ; p = 0.04 ) and SSIs after open surgery ( 21.4 vs. 13.2 % ; OR 0.56 , 90 % CI 0.34–0.92 ; p = 0.03 ) . The estimated cost of the intervention was $ 19.26/case and the net total amount saved during the post-intervention period was $ 65,625 month . Conclusions This bundled intervention led to a significant decrease in the overall SSI rate and was cost effective . The largest decreases in SSIs were in incisional infections and following open surgery Purpose and hypothesis The main purpose of the study is to put focus on the costs related to treating posterior cruciate ligament ( PCL ) injuries and the possible implication s of chosen treatment strategy to the respective institutions and society . Methods Costs of treating PCL injuries nonoperatively and for both single-bundle ( SB ) and double-bundle ( DB ) reconstruction were estimated . These costs were translated into equivalent quality -adjusted life years ( QALY ) given a threshold value of Euro ( € ) 70,000 per QALY . Expected gain in knee osteoarthritis outcome score ( KOOS ) quality of life ( QoL ) following surgery based on KOOS data from 112 patients was used as a basis for calculating the cost efficiency ratio . Results The average calculated cost of nonoperative treatment was € 3382 . Incremental cost for SB PCLR was € 8585 ( 154 % ) and another increment of € 5220 ( 61 % ) for DB PCLR using numbers from a European hospital . This is equivalent to increments of 0.074 ( SB ) and another 0.075 ( DB ) QALYs given the € 70,000 threshold . For DB to be as cost efficient as SB reconstruction , the incremental gain in KOOS QoL has to be at the same level as for SB reconstruction compared to nonoperative treatment . Conclusion Though surgical reconstruction adds a substantial cost to nonoperative treatment alone , it can be considered cost-effective . Double-bundle reconstruction is less cost efficient than SB reconstruction , but should probably still be considered the treatment of choice for certain patient categories . R and omized controlled trials looking at outcome following nonoperative , SB and DB PCL reconstruction are needed . The clinical relevance of this is that surgical reconstruction of PCL injuries is a cost-efficient treatment alternative in patients with an isolated PCL injury . This finding should be taken into consideration when deciding on how to treat these injuries . Level of evidence III Objective To complete an economic evaluation within a r and omised controlled trial ( RCT ) comparing the use of an electronic discharge communication tool ( eDCT ) compared with usual care . Setting Patients being discharged from a single tertiary care centre ’s internal medicine Medical Teaching Units . Participants Between January 2012 and December 2013 , 1399 patients were r and omised to a discharge mechanism . Forty-five patients were excluded from the economic evaluation as they did not have data for the index hospitalisation cost ; 1354 patients contributed to the economic evaluation . Intervention eDCT generated at discharge containing structured content on reason for admission , details of the hospital stay , treatments received and follow-up care required . The control group was discharged via traditional dictation methods . Primary and secondary outcome measures The primary economic outcome was the cost per quality -adjusted life year ( QALY ) gained . Secondary outcomes included the cost per death avoided and the cost per readmission avoided . Results The average transcription cost was $ C22.28 per patient , whereas the estimated cost of the eDCT was $ C13.33 per patient . The cost per QALY gained was $ C239 933 in the eDCT arm compared with usual care due to the very small gains in effectiveness and approximately $ C800difference in re source utilisation costs . The bootstrap analyses result ed in eDCT being more effective and more costly in 29.2 % of sample s , less costly and more effective in 29.2 % of sample s , less effective and more costly in 23.9 % of sample s and finally , less costly and less effective in 17.7 % of sample s. Conclusions The eDCT reduced per patient costs of the generation of discharge summaries . The bootstrap estimates demonstrate considerable uncertainty supporting the finding of neutrality reported in the clinical component of the RCT . The immediate transcription cost savings and previously documented provider and patient satisfaction may increase the impetus for organisations to invest in such systems , provided they have a foundation of eHealth infrastructure and readiness . Trial registration number NCT01402609 AIM Early intervention programmes are expected to result in the reduction of illness severity in patients with schizophrenia , and contain health-care costs by reducing hospital admissions and improving the social functioning of patients . This study aim ed to investigate the cost-effectiveness of treatment in an early intervention programme in comparison to st and ard care . METHODS Retrospective analysis of data prospect ively recorded in an urban area ( Milan , Italy ) . Twenty-three patients from an early intervention programme and 23 patients from st and ard care with first-episode psychosis were evaluated on their use of services over a 5-year period . The Health of the Nation Outcome Scale was used to measure clinical status . RESULTS Significant changes with respect to initial assessment were recorded on the Health of the Nation Outcome Scale , with larger effect sizes in the early intervention programme than in the st and ard care group . Consequently , the cost-effectiveness ratio per reduced score of severity was lower in the early intervention programme than in st and ard care ( € 4802 vs. € 9871 ) , with an incremental cost-effectiveness ratio , or net saving of € -1204 for every incremental reduced score of severity . Over time , greater recourse to hospital and residential facilities to obtain comparable improvement in symptoms result ed in a steady cost increase for the patients in st and ard care . CONCLUSIONS Allocation of funds to specialized early intervention programmes is the best alternative , as it can save costs by reducing the use of hospitals and residential facilities , and may produce net savings of costs in the long term Context Is it cost-effective to screen older adults for abdominal aortic aneurysm ( AAA ) ? Contribution This 7-year follow-up report of a large r and omized trial in the United Kingdom found that men age 65 to 74 years who were invited to have ultrasonography and surveillance for AAA had lower mortality rates than did those who were not invited ( hazard ratio , 0.53 [ CI , 0.42 to 0.68 ] ) . Cost-effectiveness for AAA-related deaths , based on costs applied to the events experienced by the men , was estimated at $ 19500 ( CI , $ 12400 to $ 39800 ) per life-year gained . Caution s Only men were studied . Actual costs of screening and surveillance may vary substantially in different setting s. The Editors A fast-growing body of literature is providing evidence in favor of screening men for abdominal aortic aneurysm ( AAA ) . Several large , r and omized trials published in the past few years ( 14 ) have consistently shown that screening reduces AAA-related mortality . A few observational studies of programs under way in localized areas have established the feasibility of systematic screening and have explored its practical implementation ( 57 ) . In addition to the mortality benefit , evidence indicating that screening is highly cost-effective is increasing ( 811 ) . In light of this evidence , national screening programs are now being considered in many countries ( 1214 ) . However , there is little evidence regarding long-term outcomes after AAA screening ; almost all of the evidence from r and omized trials is limited to the first 4 years after screening ( 14 ) . Moreover , long-term cost-effectiveness has been estimated only through health economic modeling ( 10 ) . We describe cost-effectiveness based on 7-year follow-up from the largest of the 4 trials of AAA screeningthe Multicentre Aneurysm Screening Study ( MASS ) ( 2 ) . The trial r and omly assigned approximately 67800 men age 65 to 74 years to receive an invitation to screening or to not receive an invitation . At 4-year follow-up , the trial reported a substantial relative reduction of 42 % ( 95 % CI , 22 % to 58 % ) in AAA-related mortality and an incremental cost-effectiveness ratio of $ 44900 ( CI , $ 24000 to $ 231000 ) per life-year gained ( 9 ) , which is at the borderline of the commonly accepted threshold for interventions . All values are reported in U.S. dollars ( U.K. 1 = U.S. $ 1.58 ) ( 15 ) . The costs of AAA screening are primarily incurred at the start of the program , but benefits continue to accrue in terms of life-years gained in patients in whom AAA rupture is avoided through elective surgery . It is therefore expected that cost-effectiveness of screening will improve over time . The mid-term results of MASS provide reliable , trial-based information regarding clinical outcomes and cost-effectiveness over a longer period . Methods The details of the MASS protocol were described previously ( 2 ) , but a brief summary is provided ( Figure 1 ) . Between 1997 and 1999 , a population -based sample of 70495 men age 65 to 74 years from 4 centers in the United Kingdom was identified by obtaining records for every man in this age range who was registered with a family physician ( registered persons account for approximately 98 % of the population ) . Persons who were ineligible for the trial ( incorrect details , known AAA , previous AAA surgery , or terminal illness ) were excluded before r and omization . The remaining 67770 men were r and omly assigned to receive an invitation to ultrasonography for AAA or to not receive an invitation to ultrasonography . At screening , men with an aortic diameter of 3.0 cm or greater were defined as having an AAA and were subsequently invited for recall scans to monitor growth of the aneurysm . Men with an aortic diameter of 3.0 to 4.4 cm were rescreened every year , and those with an aortic diameter of 4.5 to 5.4 cm were rescreened every 3 months . Participants were considered for elective surgery when the aortic diameter reached 5.5 cm , aortic expansion was 1.0 cm or more in 1 year , or they experienced symptoms attributable to the aneurysm . Men with an aortic diameter less than 3.0 cm on the initial scan were not rescreened . Blood pressure was also measured ; although family physicians were informed of these measurements , no further intervention was provided through the screening program . We obtained approval from local ethics committees at each center , and all patients who had screening provided signed informed consent . Figure 1 . Study flow diagram . Additional data on follow-up scans and AAA surgeries were collected from hospital records . Deaths up to 31 March 2005 were confirmed by the U.K. Office of National Statistics after matching of the unique National Health Service number for each person . Follow-up ranged from 5.9 to 8.2 years ( mean , 7.1 years ) . The primary outcome of interest , AAA-related mortality , is defined as all deaths within 30 days of any AAA surgery ( elective or emergency ) plus all deaths with International Classification of Diseases , Ninth Revision , codes 441.3 ( ruptured abdominal aortic aneurysm ) , 441.4 ( abdominal aortic aneurysm without mention of rupture ) , 441.5 ( ruptured aortic aneurysm at unspecified site ) , or 441.6 ( aortic aneurysm at unspecified site without mention of rupture ) . The use of codes 441.5 and 441.6 may result in inclusion of some thoracic aortic aneurysm deaths . Investigation of the accuracy of cause-of-death coding on the death certificates was done by an independent mortality working party that was blinded to group allocation . The results of this analysis showed that inaccuracies in coding did not have an important impact on study outcomes ( 2 ) . Statistical Analysis All analyses were done by using Stata , version 9 ( Stata Corp. , College Station , Texas ) . Deaths related to AAA ( primary analysis ) and all-cause mortality ( secondary analysis ) were compared between the 2 r and omized groups by using unadjusted Cox regression by intention-to-treat analysis . Adjustment for age at baseline did not influence the results . The proportional hazards assumption was tested by using Schoenfeld residuals . An unbiased r and omization-based estimate of the benefit of screening was also obtained ( 16 ) . This estimate is calculated by subtracting from the control group a subgroup that is equivalent in terms of survival to the nonadherent subgroup in the invited group . Thus , the remaining controls are comparable to the group of invited patients who attended screening . Life-years gained are estimated as the area between the KaplanMeier curves for both groups ( 17 ) . The cost-effectiveness of screening is estimated from a health service perspective for follow-up truncated at 7 years , with adjustment for censoring ( 18 ) . Details of the costing exercise in the trial at 20002001 prices were reported previously ( 9 ) . The unit costs obtained ( U.K. 1 = U.S. $ 1.58 for the year 2000 [ 15 ] ) are inflated to the 20042005 financial-year level by using annual hospital and community health services pay and price inflation indices ( 19 ) . Costs are applied to the following events on the basis of individual re source use : invitation to screening ( $ 2.46 ) , reinvitation after nonresponse ( $ 2.42 ) , initial scan ( $ 35.95 ) , recall scan ( $ 86.74 ; done in the hospital rather than in the community and including costs for periodic routine meetings with a consultant ) , consultation for elective surgery ( $ 583.79 ) , elective AAA surgery ( $ 13015.74 ) , and emergency AAA surgery ( $ 21054.32 ) . Costs relating to scans of incidentally detected AAAs in the control group are not included ( data not available ) , but costs relating from result ant AAA repair surgery are included . Sensitivity analyses were done by using 1 ) costs retained at the 20002001 financial-year level for comparison with previous publications , 2 ) quality -adjusted life-years based on age-related reductions , 3 ) U.S.-based unit cost estimates for scans and surgeries , 4 ) an increase of 50 % in the cost of a consultation ( a U.S.-based estimate was not available , but this analysis reflects possible additional assessment s ) , 5 ) 3 and 4 combined . Quality -of-life adjustments are made only on the basis of age , with an adjustment of 0.78 for life-years gained between the ages 65 and 74 years and an adjustment of 0.75 for life-years gained at ages older than 75 years ( 20 ) . The U.S.-specific estimates for scans ( initial and recall ) are based on Medicare reimbursement for AAA screening at $ 90.95 ( Current Procedural Terminology code G0389 ) ( 21 ) , and U.S.-specific costs for surgeries are based on previously published estimates ( 22 , 23 ) that were inflated to 2004 prices ( 24 ) : $ 18160 for elective procedures and $ 31106 for emergency procedures . Discounting is applied at the current recommended values of 3 % per annum for costs and effects ( 25 ) . Estimates of AAA-related costs and effects take into account the rate of nonAAA-related deaths across both groups over time . The Fieller method is used to calculate bounds for the CI for cost-effectiveness ( 26 , 27 ) . Role of the Funding Source This study was funded by the Medical Research Council . The funding source had no role in the design , implementation , or analysis of the study . Results Figure 1 shows the flow of participants through the trial . Numbers differ slightly from earlier publications because of identification of a few duplicate records in the data base . Of 67770 r and omly assigned men , 33883 were invited to be screened : 27204 ( 80 % ) attended and 1334 ( 4.9 % ) AAAs were identified . The mean age at r and omization was 69.2 years in both groups . Loss to follow-up because of death was 2.1 % overall ( 2.2 % in the control group and 2.1 % in the invited group ) . Loss to clinical follow-up ( nonattendance at recall scans ) was 19 % at 4 years and 24 % at 7 years . The Appendix Table shows surgeries and deaths within 30 days in each of the r and omly assigned groups . A few endovascular operations are included in these figures6 in the control group and 14 in the invited group . As expected , the total number of elective procedures is greater in the invited group than in the control group Objective : To evaluate the safety and cost-effectiveness of short-stay intensive care ( SSIC ) treatment for low-risk coronary artery bypass patients . Design : R and omized clinical equivalence trial . Setting : University Hospital Maastricht , the Netherl and s. Patients : Low-risk coronary artery bypass patients . Interventions : A total of 600 patients were r and omly assigned to undergo either SSIC treatment ( 8 hrs of intensive care treatment ) or control treatment ( care as usual , overnight intensive care treatment ) . Measurements : The primary outcome measures were intensive care readmissions and total hospital stay . The secondary outcome measures were total hospital costs , quality of life , postoperative morbidity , and mortality . Hospital costs consisted of the cost of hospital admission or admissions and outpatient costs . Main Results : The difference in intensive care readmission between the two groups of 1.13 % was very small and not significantly different ( p = .241 ; 95 % confidence interval , −0.9 % to 2.9 % ) . The total hospital stay ( p = .807 ; 95 % confidence interval , 1.2 to −0.4 ) and postoperative morbidity were comparable between the groups . The SSIC group 's quality of life improved more compared with the control group 's quality of life ( p = .0238 ; 95 % confidence interval , 0.0012 to 0.0464 ) . The total hospital costs for SSIC were significantly lower ( 95 % confidence interval , & U20AC;−1,581 to & U20AC;−174 ) compared with those for the control group ( & U20AC;4,625 and & U20AC;5,441 , respectively ) . The estimated incremental cost-effectiveness ratio ( cost/delta quality -adjusted life months ) thus showed the dominance of SSIC . Bootstrap and sensitivity analyses confirm the robustness of the study findings . Conclusions : Compared with usual care , SSIC is a safe and cost-effective approach . SSIC can be considered as an alternative for conventional postoperative intensive care treatment for low-risk coronary artery bypass graft patients Background Overweight and obesity during pregnancy is common , although robust evidence about the economic implication s of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking . We conducted a health economic evaluation in parallel with the LIMIT r and omised trial . Women with a singleton pregnancy , between 10 + 0 - 20 + 0 weeks , and BMI ≥25 kg/m2 were r and omised to Lifestyle Advice ( a comprehensive antenatal dietary and lifestyle intervention ) or St and ard Care . The economic evaluation took the perspective of the health care system and its patients , and compared costs encountered from the additional use of re sources from time of r and omisation until six weeks postpartum . Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis . Mean costs and effects in the treatment groups allocated at r and omisation were compared , and incremental cost effectiveness ratios ( ICERs ) and confidence intervals ( 95 % ) calculated . Bootstrapping was used to confirm the estimated confidence intervals , and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight , and respiratory distress syndrome . Analyses utilised intention to treat principles . Results Overall , the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes , rendering the intervention cost neutral ( Lifestyle Advice Group $ 11261.19±$14573.97 versus St and ard Care Group $ 11306.70±$14562.02 ; p=0.094 ) . Using a monetary value of $ 20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg , the probability that the antenatal intervention is cost-effective is 0.85 , which increases to 0.95 when the threshold monetary value increases to $ 45,000 . Conclusions Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings , but is associated with a high probability of cost effectiveness . Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed , short-term endpoints , to more accurately estimate the value of the intervention on risk of obesity , and associated costs and health outcomes .Trials registration Australian and New Zeal and Clinical Trials Registry ( ACTRN12607000161426 ) OBJECTIVES Health decision-makers involved with coverage and payment policies are increasingly developing policies that seek information on " real-world " ( RW ) outcomes . Motivated by these initiatives , the International Society for Pharmacoeconomics and Outcomes Research ( ISPOR ) created a Task Force on Real-World Data to develop a framework to assist health-care decision-makers in dealing with RW data , especially related to coverage and payment decisions . METHODS Task Force cochairs were selected by the ISPOR Board of Directors . Cochairs selected chairs for four working groups on : clinical outcomes , economic outcomes , patient-reported outcomes , and evidence hierarchies . Task Force members included representatives from academia , the pharmaceutical industry , and health insurers . The Task Force met on several occasions , conducted frequent correspondence and exchanges of drafts , and solicited comments on three drafts from a core group of external review ers and from the ISPOR membership . RESULTS We defined RW data as data used for decision-making that are not collected in conventional r and omized controlled trials ( RCTs ) . We considered several characterizations : by type of outcome ( clinical , economic , and patient-reported ) , by hierarchies of evidence ( which rank evidence according to the strength of research design ) , and by type of data source ( supplementary data collection alongside RCTs , large simple trials , patient registries , administrative cl aims data base , surveys , and medical records ) . Our report discusses eight key issues : 1 ) the importance of RW data ; 2 ) limitations of RW data ; 3 ) the fact that the level of evidence required depends on the circumstance ; 4 ) the need for good research practice s for collecting and reporting RW data ; 5 ) the need for good process in using RW data in coverage and reimbursement decisions ; 6 ) the need to consider costs and benefits of data collection ; 7 ) the ongoing need for modeling ; and 8) the need for continued stakeholder dialogue on these topics . CONCLUSIONS Real-world data are essential for sound coverage and reimbursement decisions . The types and applications of such data are varied , and context matters greatly in determining the value of a particular type in any circumstance . It is critical that policymakers recognize the benefits , limitations , and method ological challenges in using RW data , and the need to consider carefully the costs and benefits of different forms of data collection in different situations Aims The aim was to evaluate the cost-effectiveness of primary prevention of gestational diabetes mellitus ( GDM ) through intensified counselling on physical activity , diet , and appropriate weight gain among the risk group . Material s and Methods The cost-effectiveness analysis was based on data from a cluster-r and omised controlled GDM prevention trial carried out in primary health-care maternity clinics in Finl and . Women ( n = 399 ) with at least one risk factor for GDM were included . The incremental cost-effectiveness ratio ( ICER ) was calculated in terms of birth weight , 15D , and perceived health as measured with a visual analogue scale ( VAS ) . A bootstrap technique for cluster-r and omised sample s was used to estimate uncertainty around a cost-effectiveness acceptability curve . Results The mean total cost in the intervention group was € 7,763 ( st and ard deviation ( SD ) : € 4,511 ) and in the usual-care group was € 6,994 ( SD : € 4,326 , p = 0.14 ) . The mean intervention cost was € 141 . The difference for costs in the birth-weight group was € 753 ( 95 % CI : −250 to 1,818 ) and in effects for birth weight was 115 g ( 95 % CI : 15 to 222 ) . The ICER for birth weight was almost € 7 , with 86.7 % of bootstrap pairs located in the north-east quadrant , indicating that the intervention was more effective and more expensive in birth weight terms than the usual care was . The data show an 86.7 % probability that each gram of birth weight avoided requires an additional cost of € 7 . Conclusions Intervention was effective for birth weight but was not cost-effective for birth weight , 15D , or VAS when compared to the usual care . Trial Registration IS RCT N 33885819 Background —Use of coronary angiography after myocardial infa rct ion has been controversial , with some physicians advocating routine use and others advocating selective use only after documentation of residual myocardial ischemia . The effects of these strategies on economic outcomes have not been established . Methods and Results —We analyzed data from a r and omized , controlled clinical trial conducted in 17 Department of Veterans Affairs hospitals that enrolled 876 clinical ly uncomplicated patients 24 to 72 hours after an acute non – Q-wave myocardial infa rct ion . The routine invasive strategy included early coronary angiography with revascularization based on established guidelines . The conservative , ischemia-guided strategy included noninvasive testing with radionuclide ventriculography and exercise thallium scintigraphy , followed by coronary angiography in patients with objective evidence of myocardial ischemia . We measured the cost of hospitalization and outpatient visits and tests during follow-up and calculated the incremental cost-effectiveness ratio . The conservative , ischemia-guided strategy had lower costs than the routine invasive strategy , both during the initial hospitalization ( $ 14 733 versus $ 19 256 , P < 0.001 ) and after a mean follow-up of 1.9 years ( $ 39 707 versus $ 41 893 , P = 0.04 ) . The hazard ratio for death was 0.72 ( confidence limits , 0.51 to 1.01 ) in the conservative strategy . The conservative strategy had lower costs and better outcomes in 76 % of 1000 bootstrap replications , and a cost-effectiveness ratio below $ 50 000 per year of life added in 96 % of replications . Conclusions —A conservative , ischemia-guided strategy of selective coronary angiography and revascularization for patients who develop objective evidence of recurrent ischemia is more cost-effective than a strategy of routine coronary angiography after uncomplicated non – Q-wave myocardial infa rct ion Abstract Purpose Real‐world evidence ( RWE ) includes data from retrospective or prospect i ve observational studies and observational registries and provides insights beyond those addressed by r and omized controlled trials . RWE studies aim to improve health care decision making . Methods The International Society for Pharmacoeconomics and Outcomes Research ( ISPOR ) and the International Society for Pharmacoepidemiology ( ISPE ) created a task force to make recommendations regarding good procedural practice s that would enhance decision makers ' confidence in evidence derived from RWD studies . Peer review by ISPOR/ISPE members and task force participants provided a consensus‐building iterative process for the topics and framing of recommendations . Results The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration , replicability , and stakeholder involvement in RWE studies . These recommendations , in concert with earlier recommendations about study methodology , provide a trustworthy foundation for the exp and ed use of RWE in health care decision making . Conclusion The focus of these recommendations is good procedural practice s for studies that test a specific hypothesis in a specific population . We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers , journal editors , and other key stakeholders OBJECTIVE Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition ( IVR ) reminders for enhancing adherence to cardiovascular medications ( i.e. , statins , angiotensin-converting enzyme inhibitors [ ACEIs ] , and angiotensin receptor blockers [ ARBs ] ) . METHODS Three groups , usual care ( UC ) , IVR , and IVR plus educational material s ( IVR+ ) , with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average . Costs to implement and deliver the intervention ( from a payer perspective ) were tracked during the trial . Medical care costs and outcomes were ascertained using electronic medical records . RESULTS Per-patient intervention costs ranged from $ 9 to $ 17 for IVR and from $ 36 to $ 47 for IVR+ . For ACEI/ARB , the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ( $ 6 and $ 16 for IVR and IVR+ , respectively ) . For statins , the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ( $ 6 and $ 43 for IVR and IVR+ , respectively ) . Considering potential cost offsets from reduced cardiovascular events , the probability of breakeven was the highest for UC , but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein ( LDL ) level of more than 100 mg/dl and those with two or more calls . CONCLUSIONS We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective , depending on a decision maker 's willingness to pay for unit increase in adherence . When considering changes in LDL level and downstream medical care offsets , UC is the optimal strategy for the general population . However , IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline INTRODUCTION Recent colorectal cancer screening studies focus on optimizing adherence . This study evaluated the cost effectiveness of interventions using electronic health records ( EHRs ) ; automated mailings ; and stepped support increases to improve 2-year colorectal cancer screening adherence . METHODS Analyses were based on a parallel- design , r and omized trial in which three stepped interventions ( EHR-linked mailings [ " automated " ] ; automated plus telephone assistance [ " assisted " ] ; or automated and assisted plus nurse navigation to testing completion or refusal [ navigated " ] ) were compared to usual care . Data were from August 2008 to November 2011 , with analyses performed during 2012 - 2013 . Implementation re sources were micro-costed ; research and registry development costs were excluded . Incremental cost-effectiveness ratios ( ICERs ) were based on number of participants current for screening per guidelines over 2 years . Bootstrapping examined robustness of results . RESULTS Intervention delivery cost per participant current for screening ranged from $ 21 ( automated ) to $ 27 ( navigated ) . Inclusion of induced testing costs ( e.g. , screening colonoscopy ) lowered expenditures for automated ( ICER=-$159 ) and assisted ( ICER=-$36 ) relative to usual care over 2 years . Savings arose from increased fecal occult blood testing , substituting for more expensive colonoscopies in usual care . Results were broadly consistent across demographic subgroups . More intensive interventions were consistently likely to be cost effective relative to less intensive interventions , with willingness to pay values of $ 600-$1,200 for an additional person current for screening yielding ≥80 % probability of cost effectiveness . CONCLUSIONS Two-year cost effectiveness of a stepped approach to colorectal cancer screening promotion based on EHR data is indicated , but longer-term cost effectiveness requires further study The inhaled Steroid Treatment As Regular Therapy in early asthma ( START ) study has shown that early intervention with inhaled budesonide in mild persistent asthma improves clinical outcomes in both adults and children . The aim of this study was to estimate the incremental cost-effectiveness of early treatment with budesonide Turbuhaler in children aged 5 - 10 yr who participated in START . Direct and indirect costs associated with asthma were determined for 1974 children participating in the double-blind , 3-year part of the study . R and omization was to placebo or to budesonide 200 microg once daily in each case in addition to usual asthma care . Cost-effectiveness ratios were calculated from the healthcare payer 's and societal perspectives ( using US prices ) . The addition of once-daily budesonide therapy to usual asthma care was associated with 16 additional symptom-free days ( SFDs ) per child over the 3-yr period ( p < 0.001 ) , with a substantial reduction ( 50 % ) in the mean number of days spent in hospital , and with reduced frequency of emergency room visits and missed school and caregiver work days . From the healthcare payer 's perspective ( direct costs ) , the increase in mean direct cost over 3 yr with budesonide was 169 dollars , which translated into an incremental cost of early intervention with budesonide in children of 10.50 dollars ( 95 % CI 1.20 - 33.30 dollars ) per SFD gained . From the societal perspective , there was a cost reduction over 3 yr of 192 dollars with budesonide relative to placebo . From a societal perspective , budesonide was therefore dominant . In conclusion , early intervention with once-daily budesonide added to usual asthma care in children with mild persistent asthma is cost-saving from a societal perspective and is acceptably cost-effective when viewed from a healthcare payer perspective Abstract Background : Cardiovascular disease is one of the leading causes of death and it has been shown that primary prevention with the HMG-CoA reductase inhibitor ( statin ) lipid-lowering drugs can reduce cardiovascular events . Acquisition costs vary between statins and this may be an important consideration in the overall cost effectiveness ( CE ) of different options . Objective : To perform a CE study of the main statins used in Spain for primary prevention of cardiovascular disease in patients with high cholesterol levels . Study design : The CE analysis was based on an open-label , prospect i ve , naturalistic , r and omised intervention study under usual care conditions in primary care setting s in patients with high cholesterol levels ( total cholesterol [ TC ] > 240 mg/dL , low-density lipoprotein cholesterol [ LDL-C ] > 160 mg/dL ) and one or more cardiovascular risk factors . The analysis was conducted from the perspective of the Spanish National Health System ; the year of costing was 2001 . Patients : A total of 161 patients ( 49.7 % males ) , mean age 65 ± 10.3 years , without evidence of cardiovascular disease were included in the study . Of those , 82.1 % were hypertensive , 37.1 % had diabetes mellitus and 17.9 % were smokers . Interventions : Forty-eight patients received oral atorvastatin 10 mg/day , 32 received fluvastatin 40 mg/day , 44 received simvastatin 20 mg/day and 37 patients received pravastatin 20 mg/day for 6 months . Main measurements and results : After 6 months , the therapeutic goals of LDL-C control , according to the recommendations of the Spanish Society of Arteriosclerosis — Consensus-2000 , were reached in 62.5 % , 43.8 % , 45.5 % and 40.5 % of patients treated with atorvastatin , fluvastatin , simvastatin and pravastatin , respectively . The average CE ratio , expressed as the cost in euros ( ® ) per patient achieving the therapeutic goals , was ® 424.3 for atorvastatin , ® 503.5 for fluvastatin , ® 527.0 for simvastatin and ® 683.4 for pravastatin . The incremental CE ratios for atorvastatin versus fluvastatin and simvastatin were ® 238.9 and ® 149.5 , respectively , per additional patient reaching therapeutic goals . Atorvastatin , fluvastatin and simvastatin all dominated pravastatin . Conclusions : All the statins studied have been shown to be effective for reducing both TC and LDL-C levels . In this study , atorvastatin was the most efficient drug , with the best CE ratio ( cost per patient reaching therapeutic goals ) . Atorvastatin was more effective and less costly than pravastatin , and when compared with fluvastatin or simvastatin the additional cost per additional patient achieving therapeutic goals was < ® 250 OBJECTIVES The aim was to assess the cost-effectiveness of fenestrated and branched stent grafts ( f/b EVAR ) compared with open surgical repair ( OSR ) in thoraco-abdominal or complex abdominal aortic aneurysms ( TAAA/AAA ) at 2 years . METHODS Two matched cohorts of patients with TAAA or complex AAA were compared after a follow-up of two years . Patients included in the WINDOW French multicentre prospect i ve registry were treated by f/b EVAR , and OSR patients were extracted from the French national hospital discharge data base . All cause mortality was assessed along with readmissions and hospital costs . The association between treatment and 2 year mortality was assessed by uni/multivariate Cox regression analyses using pre- and post-operative characteristics . Incremental cost-effectiveness ratios ( ICER ) were estimated for para/juxtarenal AAA , and infra- and supra-diaphragmatic TAAA . RESULTS A total of 268 high risk patients were treated by f/b EVAR and 1678 average or low risk patients were treated with OSR during the same period . Mortality did not significantly differ between the groups ( 14.9 % vs. 11.8 % , p = .150 ) and multivariate Cox regressions did not find an association between 2 year mortality and treatment . Similar proportions of patients were readmitted at least once ( 69.7 % with f/b EVAR vs. 64.2 % with OSR , p = .096 ) but f/b EVAR patients had more readmissions on average ( 2.2 vs. 1.7 , p = .001 ) . Two year hospital costs were higher in the f/b EVAR group ( € 46,039 vs. € 22,779 , p < .001 ) . At 2 years , f/b EVAR was dominated ( more expensive and less effective ) , except in the supra-diaphragmatic TAAA subgroup with an ICER of € 42,195,800 per death averted . CONCLUSIONS f/b EVAR in high risk patients offers similar 2 year mortality to OSR performed in lower risk patients but at a higher cost . The cost is mainly driven by the cost of the stent graft , which is not compensated for by lower healthcare re source consumption . Further studies are necessary to evaluate the cost-effectiveness in low risk f/b EVAR patients who may experience fewer complications Summary The purpose of this study was to analyze the cost-effectiveness of a multifactorial fall prevention program in nursing home residents . Given a willingness-to-pay ( WTP ) of 50,000 EUR per year free of femoral fracture , the probability that the intervention is cost-effective is 83 % . Introduction Despite their increased risk of falls and fractures , nursing home residents have been neglected in economic evaluations of fall prevention programs so far . The purpose of this study was to analyze , for the first time , the cost-effectiveness of a multifactorial fall prevention program in nursing home residents . Methods This study is part of a prospect i ve , unblinded , cluster , nonr and omized , controlled study focusing on the transfer of an efficacious fall prevention program into a real-world setting . The analyzed sub sample was derived from cl aims data and consisted of data on intervention ( n = 256 , residents n = 10,178 ) and control homes ( n = 893 , residents n = 22,974 ) , representing all insurants of a sickness fund ( AOK Bavaria , Germany ) who were 65 years or older , residing in a nursing home on the 31st of March 2007 and had a level of care of ≥1 according to the classification of the statutory long-term care insurance . Time free of femoral fracture ( ICD-10 , S72 ) was used as measure of health effects . Femoral fracture-related costs and intervention costs were measured from a payer perspective . Multivariate regression models were applied . Sensitivity analyses were performed and cost-effectiveness acceptability curves computed . Results Within the first year of the intervention , femoral fracture rate was significantly reduced , result ing in a nonsignificant incremental mean time of 1.41 days free of femoral fracture . Incremental mean total direct costs were 29 EUR per resident , which was not significant . The incremental cost-effectiveness ratio ( ICER ) was 7,481 EUR per year free of femoral fracture . The probability of an ICER < 50,000 EUR per year free of femoral fracture was 83 % . Conclusion Depending on the amount the decision-maker is willing to pay for the incremental effect , the fall prevention program might be cost-effective within the first year . Future studies should exp and the range of costs and effects measured The authors tested the effectiveness and estimated the cost of several interventions aim ed at reducing drug interactions in primary care by design ing a 15-month cluster-controlled trial . The trial involved 265 family physicians and their patients who were r and omized into 4 groups : control , report ( received feedback reports ) , session ( group sessions ) , and face-to-face ( personal interviews ) . The outcome was the mean of relevant interactions detected on electronic medical records . Cost-effectiveness was defined as the incremental cost to reduce drug interactions by 1 % . The authors detected a baseline mean of 6.7 interactions per 100 patients , which was reduced to 5.3 interactions after follow-up . No improvement was seen in the report group when compared with the control group , whereas progressive improvement in the other groups was noted ( P < .001 ) . Incremental cost was higher in the face-to-face group ( 69.4 vs 50.7 ) ; cost-effectiveness results were slightly better in the session group ( 4.2 vs 4.5 ) BACKGROUND Women at low risk of pregnancy complications benefit from continuity of midwifery care , but no trial evidence exists for women with identified risk factors . We aim ed to assess the clinical and cost outcomes of caseload midwifery care for women irrespective of risk factors . METHODS In this unblinded , r and omised , controlled , parallel-group trial , pregnant women at two metropolitan teaching hospitals in Australia were r and omly assigned to either caseload midwifery care or st and ard maternity care by a telephone-based computer r and omisation service . Women aged 18 years and older were eligible if they were less than 24 weeks pregnant at the first booking visit . Those who booked with another care provider , had a multiple pregnancy , or planned to have an elective caesarean section were excluded . Women allocated to caseload care received antenatal , intrapartum , and postnatal care from a named caseload midwife ( or back-up caseload midwife ) . Controls received st and ard care with rostered midwives in discrete wards or clinics . The participant and the clinician were not masked to assignment . The main primary outcome was the proportion of women who had a caesarean section . The other primary maternal outcomes were the proportions who had an instrumental or unassisted vaginal birth , and the proportion who had epidural analgesia during labour . Primary neonatal outcomes were Apgar scores , preterm birth , and admission to neonatal intensive care . We analysed all outcomes by intention to treat . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12609000349246 . FINDINGS Publicly insured women were screened at the participating hospitals between Dec 8 , 2008 , and May 31 , 2011 . 1748 pregnant women were r and omly assigned , 871 to caseload and 877 to st and ard care . The proportion of caesarean sections did not differ between the groups ( 183 [ 21 % ] in the caseload group vs 204 [ 23 % ] in the st and ard care group ; odds ratio [ OR ] 0·88 , 95 % CI 0·70 - 1·10 ; p=0·26 ) . The proportion of women who had elective caesarean sections ( before onset of labour ) differed significantly between caseload and st and ard care ( 69 [ 8 % ] vs 94 [ 11 % ] ; OR 0·72 , 95 % CI 0·52 - 0·99 ; p=0·05 ) . Proportions of instrumental birth were similar ( 172 [ 20 % ] vs 171 [ 19 % ] ; p=0·90 ) , as were the proportions of unassisted vaginal births ( 487 [ 56 % ] vs 454 [ 52 % ] ; p=0·08 ) and epidural use ( 314 [ 36 % ] vs 304 [ 35 % ] ; p=0·54 ) . Neonatal outcomes did not differ between the groups . Total cost of care per woman was AUS$566·74 ( 95 % 106·17 - 1027·30 ; p=0·02 ) less for caseload midwifery than for st and ard maternity care . INTERPRETATION Our results show that for women of any risk , caseload midwifery is safe and cost effective . FUNDING National Health and Medical Research Council ( Australia ) BACKGROUND Hospitalists are assuming an increasing role in the care of surgical patients , but the impact of this model of care on postoperative outcomes is unknown . OBJECTIVE To determine the impact of providing a collaborative , hospitalist-led model of care on postoperative outcomes and costs among patients having hip or knee arthroplasty . DESIGN R and omized , controlled trial . SETTING Academic medical center . PARTICIPANTS 526 patients having elective orthopedic surgery who are at elevated risk for postoperative morbidity . MEASUREMENTS Length of stay , inpatient postoperative medical complications , health care provider satisfaction , and inpatient costs . INTERVENTIONS A comanagement medical Hospitalist-Orthopedic Team compared with st and ard postoperative care by orthopedic surgeons with medical consultation . RESULTS More patients in the hospitalist group were discharged from the hospital with no complications ( 61.6 % vs. 49.8 % ; difference , 11.8 percentage points [ 95 % CI , 2.8 to 20.7 percentage points ] ) . Fewer minor complications were observed among hospitalist patients ( 30.2 % vs. 44.3 % ; difference , -14.1 percentage points [ CI , -22.7 to -5.3 percentage points ] ) . Observed length of stay was not statistically different between treatment groups . However , when adjusted for discharge delays , mean length of stay for patients in the hospitalist model of care was shorter ( 5.1 days vs. 5.6 days ; difference , -0.5 day [ CI , -0.8 to -0.1 day ] ) . Total costs did not differ between groups . Orthopedic surgeons and nurses preferred the hospitalist model . LIMITATIONS Care providers and patients were aware of intervention assignments , and the study could not capture all costs associated with the hospitalist model . CONCLUSIONS The comanagement medical Hospitalist-Orthopedic Team model reduced minor postoperative complication rates with no statistically significant difference in length of stay or cost . The nurses and surgeons strongly preferred the comanagement hospitalist model . Additional research on the clinical and economic impact of the hospitalist model in other surgical population s is warranted Aims : Remote ischaemic conditioning seems to improve long-term clinical outcomes in patients undergoing primary percutaneous coronary intervention . Remote ischaemic conditioning can be applied with cycles of alternating inflation and deflation of a blood-pressure cuff . We evaluated the cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infa rct ion from the perspective of the Danish healthcare system . Methods and results : Between February 2007 and November 2008 , 251 patients with ST-elevation myocardial infa rct ion were r and omly assigned to remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention ( n=126 ) or to primary percutaneous coronary intervention alone ( n=125 ) . During a 4-year follow-up period , we used data from Danish medical registries and medical records to estimate within-trial cardiovascular medical care costs and major adverse cardiac and cerebrovascular event-free survival . After 4 years of follow-up , mean cumulative cardiovascular medical care costs were € 2763 ( 95 % confidence interval 207–5318 , P=0.034 ) lower in the remote ischaemic conditioning group than in the control group ( € 12,065 vs. € 14,828 ) , while mean major adverse cardiac and cerebrovascular event-free survival time was 0.30 years ( 95 % confidence interval 0.03–0.57 , P=0.032 ) higher in the remote ischaemic conditioning group than in the control group ( 3.51 vs. 3.21 years ) . In the cost-effectiveness plane , remote ischaemic conditioning therapy was economically dominant ( less costly and more effective ) in 97.26 % of 10,000 bootstrap replications . Conclusion : Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention appears to be a cost-effective treatment strategy in patients with ST-elevation myocardial infa rct ion Study Design . Retrospective comparative study . Objective . The purpose of this study is to compare functional outcomes , hospital re source utilization , and spine-related costs during 2 years in patients who had undergone primary or revision surgery for adult spinal deformity ( ASD ) . Summary of Background Data . After surgery for ASD , patients may require revision for pseudarthrosis , implant complications , or deformity progression . Data evaluating cost-effectiveness of primary and , in particular , revision surgery , for ASD are sparse . Methods . We retrospectively review ed records for 119 consecutive patients who had undergone primary or revision surgery for ASD . Two-year total spine-related medical costs were derived from hospital charge data . Functional outcome scores were extracted from prospect ively collected patient data . Cost utility ratios ( cost/ quality -adjusted life-year [ QALY ] ) at 2 years were calculated and assessed against a threshold of $ 154,458/QALY gained ( three times the 2015 US per-capita gross domestic product ) . Results . The primary surgery cohort ( n = 56 ) and revision cohort ( n = 63 ) showed significant improvements in health-related quality -of-life scores at 2 years . Median surgical and spine-related 2-year follow-up costs were $ 137,990 ( interquartile range [ IQR ] , $ 84,186 ) for primary surgery and $ 115,509 ( IQR , $ 63,753 ) for revision surgery and were not significantly different between the two groups ( P = 0.12 ) . We report 2-year QALY gains of 0.36 in the primary surgery cohort and 0.40 in the revision group ( P = 0.71 ) . Primary instrumented fusion was associated with a median 2-year cost per QALY of $ 197,809 ( IQR , $ 187,350 ) versus $ 129,950 ( IQR , $ 209,928 ) for revision surgery ( P = 0.31 ) . Conclusion . Revision surgery had lower total 2-year costs and higher QALY gains than primary surgery for ASD , although the differences were not significant . Although revision surgery for ASD is known to be technically challenging and to have a higher rate of major complications than primary surgery , revision surgery was cost-effective at 2 years . The cost/QALY ratio for primary surgery for ASD exceeded the threshold for cost effectiveness at 2 years . Level of Evidence : OBJECTIVES Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or r and omized control trials , but evidence integrating real-world survival , cost , and utility data is limited . METHODS A propensity score-matched cohort of 6856 elderly ( ≥65 years ) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance , Epidemiology , and End Results -Medicare data cohort were included . Treatment regimens ( i.e. , no chemotherapy , platinum-based only , platinum plus taxane , and other nonplatinum ) were identified in the 6 months postdiagnosis . Patients were followed until death or end of study ( December 2006 ) . Effectiveness was measured in quality -adjusted life-years ( QALYs ) , and total health care costs were measured by using a payer 's perspective ( 2009 US dollars ) . Method ological and statistical uncertainties were accounted by including alternative scenarios ( for utility values ) and net monetary benefit approach . Incremental cost-effectiveness ratios ( ICERs ) were calculated , and stratified analyses were performed by tumor stages and age groups . RESULTS On comparing the platinum-based group versus no chemotherapy , we found that the ICER was $ 30,073/QALY and $ 58,151/QALY for early- and late-stage disease , respectively , while other nonplatinum and platinum plus taxane groups were dominated ( less effective and more costly ) . Similar results were found across alternative scenarios and age groups . For patients 85 years or older , platinum plus taxane , however , was not dominated by the platinum-based group , with an ICER of $ 133,892/QALY . CONCLUSIONS Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life , we found that treatment with platinum-based regimen was the most cost-effective treatment alternative In a retrospective study , we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation ( PBSCT ) ( n = 30 ) compared with bone marrow transplantation ( BMT ) ( n = 110 ) in children with acute leukemia after 1 year of follow-up . Treatment success was defined as disease-free survival at 1 year posttransplantation . For patients at st and ard risk for disease , the treatment success rate was 57.1 % for PBSCT recipients and 80.3 % for BMT recipients ( P = not significant [ NS ] ) . The average total cost per treatment success at 1 year in the st and ard-risk disease group was $ 512,294 for PBSCT recipients and $ 352,885 for BMT recipients ( P = NS ) . For patients with high-risk disease , the treatment success rate was 18.8 % for PBSCT recipients and 23.5 % for BMT recipients ( P = NS ) . The cumulative average cost was $ 457,078 in BMT recipients and $ 377,316 in PBSCT recipients ( P = NS ) . Point estimates of the incremental cost-effectiveness ratio ( ICER ) indicate that in patients with st and ard-risk disease , allogeneic BMT had lower costs and greater effectiveness than PBSCT ( ICER , -$687,108 ; 95 % confidence interval [ CI ] , $ 2.4 million to dominated ) . For patients with high-risk disease , BMT was more effective and more costly , and it had an ICER of $ 1.69 million ( 95 % CI , $ 29.7 million to dominated ) per additional treatment success . The comparative economic evaluation provides support for BMT in st and ard-risk patients , but much uncertainty precludes a clear advantage of either treatment option in patients with high-risk disease . More studies using larger and r and omized controlled trials are needed to confirm the long-term cost-effectiveness of each procedure Real-world evidence ( RWE ) is the clinical evidence about benefits or risks of medical products derived from analyzing real world data ( RWD ) , which are data collected through routine clinical practice . This article discusses the advantages and disadvantages of RWE studies , how these studies differ from r and omized controlled trials ( RCTs ) , how to overcome barriers to current skepticism about RWE , how FDA is using RWE , how to improve the quality of RWE , and finally the future of RWE trials |
571 | 28,326,566 | There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC .
CONCLUSIONS Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC , with adalimumab being inferior to infliximab or combination therapy .
Infliximab and adalimumab were similar in CD | BACKGROUND Mucosal healing is an important therapeutic endpoint in the management of Crohn 's disease ( CD ) and ulcerative colitis ( UC ) .
Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome .
AIM To perform a systematic review and meta- analysis of biologics for induction and maintenance of mucosal healing in Crohn 's disease and ulcerative colitis . | Objective To evaluate the efficacy of certolizumab pegol ( CZP ) in improving endoscopic lesions in patients with active ileocolonic Crohn 's disease ( CD ) . Methods This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease ( ulceration in ≥2 intestinal segments with a Crohn 's Disease Endoscopic Index of Severity ( CDEIS ) score ≥8 points ) . Patients received subcutaneous CZP 400 mg at weeks 0 , 2 and 4 and every 4 weeks up to week 52 . Endoscopic evaluations were performed at weeks 0 , 10 and 54 . The primary outcome was mean change in CDEIS score at week 10 ; secondary outcome measures included endoscopic response ( decrease in CDEIS score > 5 points ) , remission ( CDEIS score < 6 ) , complete remission ( CDEIS score <3 ) and mucosal healing ( no ulcer ) at weeks 10 and 54 . Results In the intention-to-treat population ( n=89 ) the mean±SD CDEIS score was 14.5±5.3 at baseline ; the mean decrease in CDEIS score at week 10 was 5.7 ( 95 % CI 4.6 to 6.8 , p<0.0001 ) . Rates of endoscopic response , endoscopic remission , complete endoscopic remission and mucosal healing at week 10 were 54 % , 37 % , 10 % and 4 % , respectively . At week 54 the corresponding rates were 49 % , 27 % , 14 % and 8 % , respectively . The safety profile was consistent with that of previous CZP trials . Conclusions Following CZP treatment in patients with active CD , endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates . These benefits were achieved as early as week 10 and were generally maintained through week 54 . Clinical Trial Registration Number NCT00297648 BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients Objective The aim of this study was to assess the efficacy and safety of adalimumab ( ADA ) , a recombinant human monoclonal antibody against tumour necrosis factor α ( TNF ) , for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis . Methods This 8-week , multicentre , r and omised , double-blind , placebo-controlled study ( NCT00385736 ) , conducted at 94 centres in North America and Europe , enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and /or immunosuppressants . Under the original study protocol , 186 patients were r and omised ( 1:1 ) to subcutaneous treatment with ADA160/80 ( 160 mg at week 0 , 80 mg at week 2 , 40 mg at weeks 4 and 6 ) or placebo . Subsequently , at the request of European regulatory authorities , the protocol was amended to include a second induction group ( ADA80/40 : 80 mg at week 0 , 40 mg at weeks 2 , 4 and 6 ) . The primary efficacy endpoint was clinical remission ( Mayo score ≤2 with no individual subscore > 1 ) at week 8 , assessed in 390 patients r and omised ( 1:1:1 ) to ADA160/80 , ADA80/40 , or placebo . Safety was assessed in all enrolled patients . Patients , study site personnel , investigators , and the sponsor were blinded to treatment assignment . Results At week 8 , 18.5 % of patients in the ADA160/80 group ( p=0.031 vs placebo ) and 10.0 % in the ADA80/40 group ( p=0.833 vs placebo ) were in remission , compared with 9.2 % in the placebo group . Serious adverse events occurred in 7.6 % , 3.8 % and 4.0 % of patients in the placebo , ADA80/40 , and ADA160/80 groups , respectively . There were two malignancies in the placebo group , none in the ADA groups . There were no cases of tuberculosis and no deaths . Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and /or immunosuppressants . Clinical trial NCT00385736 OBJECTIVES : Studies evaluating the correlation between the widely used Simple Endoscopic Score for Crohn 's disease ( SES-CD ) and noninvasive markers are scarce . The aim of this study was to evaluate the correlation between the SES-CD and fecal calprotectin , C-reactive protein ( CRP ) , blood leukocytes , and the Crohn 's disease activity index ( CDAI ) . METHODS : Crohn 's disease patients undergoing complete ileocolonoscopy were prospect ively enrolled and scored independently according to the SES-CD and the CDAI . SES-CD was defined as follows : inactive 0–3 ; mild 4–10 ; moderate 11–19 ; and high ≥20 . RESULTS : Values in CD patients ( n=140 ileocolonoscopies ) compared with controls ( n=43 ) are as follows : calprotectin , 334±322 vs. 18±5 μg/g ; CRP , 26±29 vs. 3±2 mg/l ; and blood leukocytes , 9.1±3.4 vs. 5.4±1.9 g/l ( all P<0.001 ) . The SES-CD correlated closest with calprotectin ( Spearman 's rank correlation coefficient r=0.75 ) , followed by CRP ( r=0.53 ) , blood leukocytes ( r=0.42 ) , and the CDAI ( r=0.38 ) . Calprotectin was the only marker that could discriminate inactive endoscopic disease from mild activity ( 104±138 vs. 231±244 μg/g , P<0.001 ) , mild from moderate activity ( 231±244 vs. 395±256 μg/g , P=0.008 ) , and moderate from high activity ( 395±256 vs. 718±320 μg/g , P<0.001 ) . The overall accuracy for the detection of endoscopically active disease was 87 % for calprotectin ( cutoff 70 μg/g ) , 66 % for elevated CRP , 54 % for blood leukocytosis , and 40 % for the CDAI ≥150 . CONCLUSIONS : Fecal calprotectin correlated closest with SES-CD , followed by CRP , blood leukocytes , and the CDAI . Furthermore , fecal calprotectin was the only marker that reliably discriminated inactive from mild , moderate , and highly active disease , which underlines its usefulness for activity monitoring Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Adalimumab is a fully human , monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis ( UC ) . Methods This 52-week , phase 2/3 , r and omized , double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF – naive Japanese patients with UC who were refractory to corticosteroids , immunomodulators , or both . Patients received placebo , adalimumab 80/40 ( 80 mg at week 0 , then 40 mg every other week ) , or adalimumab 160/80 ( 160/80 mg at weeks 0/2 , then 40 mg every other week ) in addition to background UC therapy . Results At week 8 , remission rates were similar among treatment arms , but more patients treated with adalimumab 160/80 achieved response ( placebo , 35 % ; 80/40 , 43 % ; 160/80 , 50 % ; P = 0.044 for 160/80 vs placebo ) and mucosal healing ( placebo , 30 % ; 80/40 , 39 % ; 160/80 , 44 % ; P = 0.045 for 160/80 vs placebo ) compared with placebo . At week 52 , more patients receiving adalimumab 40 mg every other week achieved response ( 18 vs 31 % ; P = 0.021 ) , remission ( 7 vs 23 % ; P = 0.001 ) , and mucosal healing ( 16 vs 29 % ; P = 0.015 ) compared with placebo . Week 8 response to adalimumab was associated with greater rates of response ( 61 % ) , remission ( 46 % ) , and mucosal healing ( 57 % ) at week 52 relative to the overall population . Rates of serious adverse events were similar between treatment arms . Conclusions Induction with adalimumab 160/80 mg led to early response and mucosal healing . Maintenance adalimumab had greater rates of long-term response , remission , and mucosal healing compared with placebo . No new safety signals were identified BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . Background : Observational studies have demonstrated that mucosal healing ( MH ) may be associated with reductions in hospitalizations and surgeries for moderate to severe Crohn 's disease ( CD ) . Whether treatment to achieve MH is a cost-effective endpoint has not been established previously . Methods : We constructed a decision analytic model comparing two treatment strategies . In the clinical response ( CR ) arm , patients not in clinical remission at year 1 are dose-escalated . In the MH arm , patients with persistence of mucosal ulcerations at year 1 are escalated irrespective of clinical symptoms . Patients remain at risk for hospitalization and surgeries while they have active disease . We examined a 2-year time horizon . Results : In the base case the MH strategy was more effective at 2 years ( quality -adjusted life year [ QALY ] 0.71 ) compared to the CR strategy ( QALY 0.69 ) but was also more expensive with an incremental cost-effectiveness ratio ( ICER ) of $ 49,278/QALY gained . In a hypothetical cohort of 100,000 patients assigned to each treatment arm , the MH strategy result ed in lower rates of hospitalization and surgery with a number needed to treat of 27 and 106 , respectively . The results were sensitive to the ability of infliximab to achieve MH and the incremental benefit of MH over clinical remission . Conclusions : We demonstrate that MH as an endpoint is a cost-effective strategy in CD patients initiating IFX therapy . Further prospect i ve studies on durability of MH and its incremental benefit as well as the ability of other available biologic agents to achieve MH are necessary to vali date our findings BACKGROUND & AIMS Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α . Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled , double-blind trial . METHODS Ulcerative colitis long-term remission and maintenance with adalimumab 2 ( ULTRA 2 ) was a r and omized , double-blind , placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with moderate-to-severe ulcerative colitis who received concurrent treatment with oral corticosteroids or immunosuppressants . Patients were stratified based on prior exposure to TNF-α antagonists ( either had or had not been previously treated with anti-TNF-α ) and r and omly assigned to groups given adalimumab 160 mg at week 0 , 80 mg at week 2 , and then 40 mg every other week or placebo . Primary end points were remission at weeks 8 and 52 . RESULTS Overall rates of clinical remission at week 8 were 16.5 % on adalimumab and 9.3 % on placebo ( P = .019 ) ; corresponding values for week 52 were 17.3 % and 8.5 % ( P = .004 ) . Among anti-TNF-α naïve patients , rates of remission at week 8 were 21.3 % on adalimumab and 11 % on placebo ( P = .017 ) ; corresponding values for week 52 were 22 % and 12.4 % ( P = .029 ) . Among patients who had previously received anti-TNF agents , rates of remission at week 8 were 9.2 % on adalimumab and 6.9 % on placebo ( P = .559 ) ; corresponding values for week 52 were 10.2 % and 3 % ( P = .039 ) . Serious adverse events occurred in 12 % of patients given adalimumab or placebo . Serious infections developed in 1.6 % of patients given adalimumab and 1.9 % given placebo . In the group given adalimumab , 1 patient developed squamous cell carcinoma and 1 developed gastric cancer . CONCLUSIONS Adalimumab was safe and more effective than placebo in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis who did not have an adequate response to conventional therapy with steroids or immunosuppressants BACKGROUND & AIMS We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn 's disease ( CD ) . METHODS A r and omized , double-blind , placebo-controlled trial ( extend the safety and efficacy of adalimumab through endoscopic healing [ EXTEND ] ) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD . The baseline degree of mucosal ulceration was documented by ileocolonoscopy . All patients received induction therapy ( subcutaneous adalimumab 160/80 mg at weeks 0/2 ) . At week 4 , patients were r and omly assigned to groups given 40 mg adalimumab or placebo every other week through week 52 . Open-label adalimumab was given to patients with flares or no response , starting at week 8 . Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52 . RESULTS Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 ( the primary end point ) versus 13 % given placebo ( P = .056 ) . At week 52 , rates of mucosal healing were 24 % and 0 , respectively ( P < .001 ) . Remission rates , based on the Crohn 's Disease Endoscopic Index of Severity , were 52 % for adalimumab and 28 % for placebo at week 12 ( P = .006 ) and 28 % and 3 % , respectively , at week 52 ( P < .001 ) . Rates of clinical remission based on the Crohn 's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 ( 47 % vs 28 % ; P = .021 ) and 52 ( 33 % vs 9 % ; P = .001 ) . Five serious ( 1 during induction and 4 during open-label therapy ) and 3 opportunistic infections ( 1 in each group during double-blind therapy and 1 during open-label therapy ) were reported ( n = 135 ) . CONCLUSIONS Following induction therapy with adalimumab , patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo BACKGROUND & AIMS The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis ( UC ) have not been evaluated previously . METHODS This r and omized , double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy , azathioprine monotherapy , or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC . Patients were assigned r and omly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0 , 2 , 6 , and 14 plus daily oral placebo capsules ; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule ; or combination therapy with the 2 drugs . Corticosteroid-free clinical remission ( primary end point , week 16 ) was evaluated at weeks 8 and 16 . The study was terminated before the enrollment target was reached . RESULTS A total of 239 patients were included in efficacy analyses . Baseline characteristics were similar between treatment groups . Corticosteroid-free remission at week 16 was achieved by 39.7 % ( 31 of 78 ) of patients receiving infliximab/azathioprine , compared with 22.1 % ( 17 of 77 ) receiving infliximab alone(P = .017 ) and 23.7 % ( 18 of 76 ) receiving azathioprine alone(P = .032 ) . Mucosal healing at week 16 occurred in 62.8 % ( 49 of 78 ) of patients receiving infliximab/azathioprine , compared with 54.6 % ( 42 of 77 ) receiving infliximab ( P = .295 ) and 36.8 % ( 28 of 76 ) receiving azathioprine ( P = .001 ) . Serious infections occurred in 2 patients ( 1 patient receiving infliximab , and 1 patient receiving azathioprine ) . CONCLUSIONS Anti – tumor necrosis factor-a – naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy . Combination therapy led to significantly better mucosal healing than azathioprine monotherapy . Clinical Trials.gov number , NCT00537316 BACKGROUND The efficacy of vedolizumab , an α4β7 integrin antibody , in Crohn 's disease is unknown . METHODS In an integrated study with separate induction and maintenance trials , we assessed intravenous vedolizumab therapy ( 300 mg ) in adults with active Crohn 's disease . In the induction trial , 368 patients were r and omly assigned to receive vedolizumab or placebo at weeks 0 and 2 ( cohort 1 ) , and 747 patients received open-label vedolizumab at weeks 0 and 2 ( cohort 2 ) ; disease status was assessed at week 6 . In the maintenance trial , 461 patients who had had a response to vedolizumab were r and omly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52 . RESULTS At week 6 , a total of 14.5 % of the patients in cohort 1 who received vedolizumab and 6.8 % who received placebo were in clinical remission ( i.e. , had a score on the Crohn 's Disease Activity Index [ CDAI ] of ≤150 , with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity ) ( P=0.02 ) ; a total of 31.4 % and 25.7 % of the patients , respectively , had a CDAI-100 response ( ≥100-point decrease in the CDAI score ) ( P=0.23 ) . Among patients in cohorts 1 and 2 who had a response to induction therapy , 39.0 % and 36.4 % of those assigned to vedolizumab every 8 weeks and every 4 weeks , respectively , were in clinical remission at week 52 , as compared with 21.6 % assigned to placebo ( P<0.001 and P=0.004 for the two vedolizumab groups , respectively , vs. placebo ) . Antibodies against vedolizumab developed in 4.0 % of the patients . Nasopharyngitis occurred more frequently , and headache and abdominal pain less frequently , in patients receiving vedolizumab than in patients receiving placebo . Vedolizumab , as compared with placebo , was associated with a higher rate of serious adverse events ( 24.4 % vs. 15.3 % ) , infections ( 44.1 % vs. 40.2 % ) , and serious infections ( 5.5 % vs. 3.0 % ) . CONCLUSIONS Vedolizumab-treated patients with active Crohn 's disease were more likely than patients receiving placebo to have a remission , but not a CDAI-100 response , at week 6 ; patients with a response to induction therapy who continued to receive vedolizumab ( rather than switching to placebo ) were more likely to be in remission at week 52 . Adverse events were more common with vedolizumab . ( Funded by Millennium Pharmaceuticals ; GEMINI 2 Clinical Trials.gov number , NCT00783692 . ) BACKGROUND Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis . METHODS We conducted two integrated r and omized , double-blind , placebo-controlled trials of vedolizumab in patients with active disease . In the trial of induction therapy , 374 patients ( cohort 1 ) received vedolizumab ( at a dose of 300 mg ) or placebo intravenously at weeks 0 and 2 , and 521 patients ( cohort 2 ) received open-label vedolizumab at weeks 0 and 2 , with disease evaluation at week 6 . In the trial of maintenance therapy , patients in either cohort who had a response to vedolizumab at week 6 were r and omly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks . A response was defined as a reduction in the Mayo Clinic score ( range , 0 to 12 , with higher scores indicating more active disease ) of at least 3 points and a decrease of at least 30 % from baseline , with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 . RESULTS Response rates at week 6 were 47.1 % and 25.5 % among patients in the vedolizumab group and placebo group , respectively ( difference with adjustment for stratification factors , 21.7 percentage points ; 95 % confidence interval [ CI ] , 11.6 to 31.7 ; P<0.001 ) . At week 52 , 41.8 % of patients who continued to receive vedolizumab every 8 weeks and 44.8 % of patients who continued to receive vedolizumab every 4 weeks were in clinical remission ( Mayo Clinic score ≤2 and no subscore > 1 ) , as compared with 15.9 % of patients who switched to placebo ( adjusted difference , 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [ 95 % CI , 14.9 to 37.2 ; P<0.001 ] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [ 95 % CI , 17.9 to 40.4 ; P<0.001 ] ) . The frequency of adverse events was similar in the vedolizumab and placebo groups . CONCLUSIONS Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis . ( Funded by Millennium Pharmaceuticals ; GEMINI 1 Clinical Trials.gov number , NCT00783718 . ) BACKGROUND & AIMS Little is known about the efficacy of golimumab , a fully human monoclonal antibody to tumor necrosis factor ( TNF ) -α , for treatment of ulcerative colitis ( UC ) . We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment . METHODS We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC ( Mayo score : 6 - 12 ; endoscopic subscore ≥ 2 ; 774 patients in phase 3 ) . Patients were r and omly assigned to groups given golimumab doses of 100 mg and then 50 mg ( phase 2 only ) , 200 mg and then 100 mg , or 400 mg and then 200 mg , 2 weeks apart . The phase 3 primary end point was week-6 clinical response . Secondary end points included week-6 clinical remission , mucosal healing , and Inflammatory Bowel Disease Question naire ( IBDQ ) score change . RESULTS In phase 2 , median changes from baseline in the Mayo score were -1.0 , -3.0 , -2.0 , and -3.0 , in the groups given placebo , 100 mg/50 mg , 200/100 mg , and 400/200 mg golimumab , respectively . In phase 3 , rates of clinical response at week 6 were 51.0 % and 54.9 % among patients given 200 mg/100 mg and 400 mg/200 mg golimumab , respectively , vs 30.3 % among those given placebo ( both , P ≤ .0001 ) . Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group ( P ≤ .0014 , all comparisons ) . Rates of serious adverse events were 6.1 % and 3.0 % , and rates of serious infection were 1.8 % and 0.5 % , in the placebo and golimumab groups , respectively . One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess . CONCLUSIONS Treatment with subcutaneous golimumab induces clinical response , remission , and mucosal healing , and increases quality of life in larger percentages of patients with active UC than placebo . Clinical Trials.gov Number : NCT00487539 BACKGROUND & AIMS Subcutaneous golimumab , a fully human monoclonal antibody to tumor necrosis factor-α ( TNFα ) , was evaluated as maintenance therapy in TNFα antagonist-naive adults with moderate-to-severe active ulcerative colitis , despite conventional therapy , who responded to golimumab induction therapy . METHODS We performed a phase 3 , double-blind trial of patients who completed golimumab induction trials ( Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment , eg , PURSUIT ) . Patients who responded to induction therapy with golimumab ( n = 464 ) were assigned r and omly to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52 . Patients who responded to placebo in the induction study continued to receive placebo . Nonresponders in the induction study received 100 mg golimumab . The primary end point was clinical response maintained through week 54 ; secondary end points included clinical remission and mucosal healing at both weeks 30 and 54 . RESULTS Clinical response was maintained through week 54 in 47.0 % of patients receiving 50 mg golimumab , 49.7 % of patients receiving 100 mg golimumab , and 31.2 % of patients receiving placebo ( P = .010 and P < .001 , respectively ) . At weeks 30 and 54 , a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing ( 27.8 % and 42.4 % ) than patients given placebo ( 15.6 % and 26.6 % ; P = .004 and P = .002 , respectively ) or 50 mg golimumab ( 23.2 % and 41.7 % , respectively ) . Percentages of serious adverse events were 7.7 % , 8.4 % , and 14.3 % among patients given placebo , 50 mg , or 100 mg golimumab , respectively ; percentages of serious infections were 1.9 % , 3.2 % , and 3.2 % , respectively . Among all patients given golimumab in the study , 3 died ( from sepsis , tuberculosis , and cardiac failure , all in patients who received 100 mg golimumab ) and 4 developed active tuberculosis . CONCLUSIONS Golimumab ( 50 mg or 100 mg ) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis ; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54 . Safety was consistent with that reported for other TNFα antagonists and golimumab in other approved indications . Clinical Trials.gov number : NCT00488631 BACKGROUND & AIMS It is not clear why some patients with ulcerative colitis ( UC ) do not respond to treatment with anti-tumor necrosis factor ( TNF ) agents , such as infliximab . It could be that some patients have high level of inflammation , with large quantities of TNF to be neutralized by the drug . We investigated whether loss of anti-TNF agents through ulcerated intestinal mucosa reduces the efficacy of these drugs in patients with severe UC . METHODS We collected fecal sample s from 30 consecutive patients with moderate to severely active UC during the first 2 weeks of infliximab therapy at the University of Amsterdam hospital . Infliximab concentrations were measured in serum and supernatants of fecal sample s using an enzyme-linked immunosorbent assay ( Sanquin Biologicals Laboratory , Amsterdam , The Netherl and s ) . Clinical and endoscopic responses were assessed 2 and 8 weeks and 3 months after treatment began . RESULTS Infliximab was detected in 129 of 195 fecal sample s ( 66 % ) ; the highest concentrations were measured in the first days after the first infusion . Patients that were clinical nonresponders at week 2 had significantly higher fecal concentrations of infliximab after the first day of treatment than patients with clinical responses ( median concentration , 5.01 μg/mL in nonresponders vs 0.54 μg/mL in responders ; P = .0047 ) . We did not observe a correlation between fecal and serum concentrations of infliximab . CONCLUSIONS Infliximab is lost into stools of patients with UC . High fecal concentrations of infliximab in the first days after therapy begins are associated with primary nonresponse . Additional studies are needed to determine how therapeutic antibodies are lost through the intestinal mucosa and how this process affects treatment response . Clinical trial ID : NL41310.018.12 Over the past years , mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases . Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn 's disease . Mucosal healing may also prevent the development of long-term disease complications , such as bowel damage in Crohn 's disease and colorectal cancer in ulcerative colitis . Histologic healing may be the ultimate therapeutic goal in ulcerative colitis , whereas its impact on the course of Crohn 's disease is unknown . Complete mucosal healing may be required before considering drug withdrawal . Targeting early Crohn 's disease is more effective than approaches aim ed at healing mucosa in longst and ing disease . Several questions remain to be answered : should mucosal healing be systematic ally used in clinical practice ? Should we optimize therapies to achieve mucosal healing ? What is the degree of intestinal healing that is required to change the disease course ? Large prospect i ve studies addressing these issues are needed |
572 | 28,944,590 | Most of the review ed studies showed a significant improvement of subjective sleep quality when using described non-pharmacological interventions ( objective parameters were not significantly vali date d ) .
Despite the heterogeneity of analysed studies and some common method ological issues ( sample size , design , outcome parameters choice and comparison ) earplugs and eye mask showed potential positive effects on sleep quality and the incidence of delirium in ICU patients | Intensive care unit ( ICU ) environment has a very strong and unavoidable negative impact on patients ' sleep .
Sleep deprivation in ICU patients has been already studied and negative effects on their outcome ( prolonged ICU stay , decreased recovery ) and complication rates ( incidence of delirium , neuropsychological sequels of critical illness ) discussed .
Several interventions potentially improving the sleep disturbance in ICU ( sleep-promotion strategies ) have been assumed and tested for clinical practice .
We present a review of recent literature focused on chosen types of non-pharmacological interventions ( earplugs and eye mask ) analysing their effect on sleep quality /quantity . | Introduction Environmental stimulus , especially noise and light , is thought to disrupt sleep in patients in the intensive care unit ( ICU ) . This study aim ed to determine the physiological and psychological effects of ICU noise and light , and of earplugs and eye masks , used in these conditions in healthy subjects . Methods Fourteen subjects underwent polysomnography under four conditions : adaptation , baseline , exposure to recorded ICU noise and light ( NL ) , and NL plus use of earplugs and eye masks ( NLEE ) . Urine was analyzed for melatonin and cortisol levels . Subjects rated their perceived sleep quality , anxiety levels and perception of environmental stimuli . Results Subjects had poorer perceived sleep quality , more light sleep , longer rapid eye movement ( REM ) latency , less REM sleep when exposed to simulated ICU noise and light ( P < 0.05 ) . Nocturnal melatonin ( P = 0.007 ) and cortisol secretion levels ( P = 0.004 ) differed significantly by condition but anxiety levels did not ( P = 0.06 ) . Use of earplugs and eye masks result ed in more REM time , shorter REM latency , less arousal ( P < 0.05 ) and elevated melatonin levels ( P = 0.002 ) . Conclusions Earplugs and eye masks promote sleep and hormone balance in healthy subjects exposed to simulated ICU noise and light , making their promotion in ICU patients reasonable AIM AND OBJECTIVE The study compared the effect of earplug-delivered sleep-inducing music on sleep in persons with percutaneous transluminal coronary angiography in the cardiac care unit . BACKGROUND Diverse types of music have been cl aim ed to improve sleeping elsewhere , but relatively little is known in South Korea . Most studies investigating the effect of sleep-inducing music on sleep have involved persons with insomnia , even though many persons with cardiovascular disease in the intensive care unit suffer from sleeping problems . There is a need to investigate the effect of sleep-inducing music on sleep disorders in persons with percutaneous transluminal coronary angiography in the cardiac care unit . DESIGN An experimental research design was used . METHODS Data collection was conducted in the cardiac care unit of K University Hospital in D city , from 3 September-4 October 2010 . Fifty-eight subjects participated and were r and omly assigned to the experimental group ( earplug-delivered sleep-inducing music for 52 min beginning at 10:00 pm , while wearing an eyeshield , n = 29 ) and the control group ( no music , but earplugs and eyeshield worn , n = 29 ) . The quantity and quality of sleep were measured using question naires at 7 am the next morning for each group . RESULTS Participants in the experimental group reported that the sleeping quantity and quality were significantly higher than control group ( t = 3·181 , p = 0·002 , t = 5·269 , p < 0·001 , respectively ) . CONCLUSION Sleep-inducing music significantly improved sleep in patients with percutaneous transluminal coronary angiography at a cardiac care unit . Offering earplugs and playing sleep-inducing music may be a meaningful and easily enacted nursing intervention to improve sleep for intensive care unit patients . RELEVANCE TO CLINICAL PRACTICE Nurses working at cardiac care unit can use music to improve sleeping in clients with percutaneous transluminal coronary angiography BACKGROUND Post-anaesthesia care units ( PACUs ) with 24/7 activity and consequently artificial light and noise may disturb the sleep of patients who require prolonged medical supervision . After one postoperative night , we compared sleep quality in patients with and without noise ( earplug ) and light ( eye mask ) protection . METHODS After ethical board approval , 46 patients without any neurological or respiratory failure undergoing major non-cardiac surgery were prospect ively included . They were r and omized to sleep with or without protective devices during the first postoperative night in the PACU . Sleep quality was simultaneously measured by sleep- quality scales ( Spiegel score and Medical Outcomes Study Sleep ) , nurses ' assessment , and through a wrist actigraph ( Actiwatch ) . Secondary outcomes such as pain control and nocturnal activity were recorded . Comparisons between groups were made by Student 's t-test or non-parametric test for repeated measures as appropriate ( SPSS 10.0 ) . A P-value < 0.05 was considered significant . RESULTS Data from 41 patients were analysed . Protective devices during the first postoperative night prevented a decrease in sleep quality compared with st and ard care , as evaluated by the Spiegel scale : 20 ( 4 ) vs 15 ( 5 ) , P=0.006 . These devices significantly decreased the need for a nap [ 50 % 95 % confidence interval ( CI ) ( 20 - 80 ) vs 95 % 95 % CI ( 85 - 100 ) , P<0.001 ] , but had no effect on sleep length evaluated by Actiwatch . The total consumption of morphine was significantly reduced in the first 24 h [ respectively , 15(12 ) mg and 27(17 ) mg , P=0.02 ] . CONCLUSIONS Earplugs and eye masks applied in the PACU during the first postoperative night significantly preserve sleep quality . Such non-invasive and cheap devices may be generalized in the PACU or in intensive care units Introduction This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium . Two research questions were formulated . First , does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU ? Second , does the use of earplugs during the night improve the quality of sleep in the ICU ? Methods A r and omized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night . The research ers were blinded during data collection . Assignment was performed by an independent nurse research er using a computer program . Eligible patients had an expected length of stay in the ICU of more than 24 hours , were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10 . Delirium was assessed using the vali date d NEECHAM scale , sleep perception was reported by the patient in response to five questions . Results The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients . A vast improvement was shown by a Hazard Ratio of 0.47 ( 95 % confidence interval ( CI ) 0.27 to 0.82 ) . Also , patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs . After the first night in the ICU , patients sleeping with earplugs reported a better sleep perception . Conclusions Earplugs may be a useful instrument in the prevention of confusion or delirium . The beneficial effects seem to be strongest within 48 hours after admission . The relation between sleep , sound and delirium , however , needs further research .Trial registration Current Controlled Trials IS RCT Background : Patients in coronary care unit are at risk of sleep deprivation . Sleep deprivation can be associated with increased blood pressure and heart rate , raising the risk of developing cardiovascular problems among patients hospitalized in coronary care unit . Objectives : This study was carried out to examine the effect of eye mask on sleep quality in cardiac patients . Patients and Methods : In this r and omized controlled trial , 60 patients who met the inclusion criteria were selected using a convenient sampling method and r and omly allocated into the experimental and control groups . Patients in the control group received routine care . However , in the experimental group , patients received routine care and eye mask for three subsequent nights . In the both groups , the sleep quality was assessed using the Pittsburgh sleep quality index . Data were analyzed by the chi-square test , independent sample s t-test , Mann-Whitney U , and Wilcoxon signed-rank tests . Results : After the study , the median scores of the subjective sleep quality , the sleep latency , the sleep duration , the habitual sleep efficiency , and the sleep disturbances domains , as well as the median score of overall Pittsburgh sleep quality index in the experimental group were significantly lower than those in the control group ( P < 0.05 ) . However , no significant differences were observed between the two groups in terms of the use of sleep medications and the daytime dysfunction domains ( P > 0.05 ) . Conclusions : Using eye mask can significantly improve the sleep quality in cardiac patients . Therefore , nurses are recommended to use eye mask in combination with current treatments for improving patients ’ sleep quality Introduction Intensive care unit ( ICU ) environmental factors such as noise and light have been cited as important causes of sleep deprivation in critically ill patients . Previous studies indicated that using earplugs and eye masks can improve REM sleep in healthy subjects in simulated ICU environment , and improve sleep quality in ICU patients . This study aim ed to determine the effects of using earplugs and eye masks with relaxing background music on sleep , melatonin and cortisol levels in ICU patients . Methods Fifty patients who underwent a scheduled cardiac surgery and were expected to stay at least 2 nights in Cardiac Surgical ICU ( CSICU ) were included . They were r and omized to sleep with or without earplugs and eye masks combined with 30-minute relaxing music during the postoperative nights in CSICU . Urine was analyzed for nocturnal melatonin and cortisol levels . Subjective sleep quality was evaluated using the Chinese version of Richards-Campbell Sleep Question naire ( a visual analog scale , ranging 0–100 ) . Results Data from 45 patients ( 20 in intervention group , 25 in control group ) were analyzed . Significant differences were found between groups in depth of sleep , falling asleep , awakenings , falling asleep again after awakening and overall sleep quality ( P < 0.05 ) . Perceived sleep quality was better in the intervention group . No group differences were found in urinary melatonin levels and cortisol levels for the night before surgery , and the first and second nights post-surgery ( P > 0.05 ) . The urinary melatonin levels of the first and second postoperative nights were significantly lower than those of the night before surgery ( P = 0.01 ) . The opposite pattern was seen with urinary cortisol levels ( P = 0.00 ) . Conclusion This combination of non-pharmacological interventions is useful for promoting sleep in ICU adult patients ; however , any influence on nocturnal melatonin levels and cortisol level may have been masked by several factors such as the timing of surgery , medication use and individual differences . Larger scale studies would be needed to examine the potential influences of these factors on biological markers and intervention efficacy on sleep . Trial registration Chinese Clinical Trial Registry : ChiCTR-IOR-14005511 . Registered 21 November 2014 Introduction Sleep deprivation is common in critically ill patients in the intensive care unit ( ICU ) . Noise and light in the ICU and the reduction in plasma melatonin play the essential roles . The aim of this study was to determine the effect of simulated ICU noise and light on nocturnal sleep quality , and compare the effectiveness of melatonin and earplugs and eye masks on sleep quality in these conditions in healthy subjects . Methods This study was conducted in two parts . In part one , 40 healthy subjects slept under baseline night and simulated ICU noise and light ( NL ) by a cross-over design . In part two , 40 subjects were r and omly assigned to four groups : NL , NL plus placebo ( NLP ) , NL plus use of earplugs and eye masks ( NLEE ) and NL plus melatonin ( NLM ) . 1 mg of oral melatonin or placebo was administered at 21:00 on four consecutive days in NLM and NLP . Earplugs and eye masks were made available in NLEE . The objective sleep quality was measured by polysomnography . Serum was analyzed for melatonin levels . Subjects rated their perceived sleep quality and anxiety levels . Results Subjects had shorter total sleep time ( TST ) and rapid eye movement ( REM ) sleep , longer sleep onset latency , more light sleep and awakening , poorer subjective sleep quality , higher anxiety level and lower serum melatonin level in NL night ( P < 0.05 ) . NLEE had less awakenings and shorter sleep onset latency ( P < 0.05 ) . NLM had longer TST and REM and shorter sleep onset latency ( P < 0.05 ) . Compared with NLEE , NLM had fewer awakenings ( P = 0.004 ) . Both NLM and NLEE improved perceived sleep quality and anxiety level ( P = 0.000 ) , and NLM showed better than NLEE in perceived sleep quality ( P = 0.01 ) . Compared to baseline night , the serum melatonin levels were lower in NL night at every time point , and the average maximal serum melatonin concentration in NLM group was significantly greater than other groups ( P < 0.001 ) . Conclusions Compared with earplugs and eye masks , melatonin improves sleep quality and serum melatonin levels better in healthy subjects exposed to simulated ICU noise and light . Trial registration Chinese Clinical Trial Registry ChiCTR-IPR-14005458 . Registered 10 November 2014 STUDY OBJECTIVES To objective ly measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population . DESIGN Prospect i ve cohort analysis . SETTING University teaching hospital medical-surgical ICU . PATIENTS Twenty critically ill ( APACHE II [ acute physiology and chronic health evaluation II ] acute physiology score [ APS ] , 10 + /- 5 ) , mechanically ventilated adults ( male 12 , female 8 , age 62 + /- 15 years ) with mild to moderate acute lung injury ( lung injury score , 1.8 + /- 0.9 ) 10 + /- 7 days after admission to the ICU . MEASUREMENTS AND RESULTS Patients were divided into three groups based on 24-h polysomnography ( PSG ) findings . No patient demonstrated normal sleep . In the " disrupted sleep " group ( n = 8) , electrophysiologic sleep was identified and was distributed throughout the day ( 6:00 AM to 10:00 PM ; 4.0 + /- 2.9 h ) and night ( 10:00 PM to 6:00 AM ; 3.0 + /- 1.9 h ) with equivalent proportions of non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) sleep . Nocturnal sleep efficiency was severely reduced ( 38 + /- 24 % ) with an increased proportion of stage 1 NREM sleep ( 40 + /- 28 % total sleep time [ TST ] ) and a reduced proportion of REM sleep ( 10 + /- 14 % TST ) . Severe sleep fragmentation was reflected by a high frequency of arousals ( 20 + /- 17/h ) and awakenings ( 22 + /- 25/h ) . Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients . These were classified either as " atypical sleep " ( n = 5 ) , characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep , or " coma " ( n = 7 ) , characterized by > 50 % delta or theta EEG activity with ( n = 5 ) and without ( n = 2 ) evidence of EEG activation either spontaneously or in response to deep painful stimuli . The combined atypical sleep and coma groups had a higher APS ( 13 + /- 4 vs 6 + /- 4 ) and higher doses of sedative medications than the disrupted sleep group . CONCLUSION Sleep , as it is conventionally measured , was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted . We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population BACKGROUND Sleep deprivation may contribute to impaired immune function , ventilatory compromise , disrupted thermoregulation , and delirium . Noise levels in intensive care units may be related to disturbed sleep patterns , but noise reduction has not been tested in this setting . OBJECTIVE To measure the effect of a noise reduction intervention on the sleep of healthy subjects exposed to simulated intensive care unit noise . METHODS After digital audiotape recording of noise and development of the noise reduction intervention , 5 nocturnal 8-hour periods of sleep were measured in 6 paid , healthy volunteers at 7-day intervals in a sleep disorders center . Polysomnographic data were collected by experienced sleep disorders technicians and scored by certified raters . After the first 3 quiet nights , earplugs were r and omly assigned to be worn on the fourth and fifth nights during exposure to the recorded noise . Sound pressure levels were measured during all 5 nights . RESULTS Sleep architecture and sound measurements on quiet nights did not differ significantly . Sound levels were significantly lower on quiet nights than on noise nights . Exposure to the noise increased the number of awakenings , percentage of stage 2 sleep , and rapid eye movement latency and decreased time asleep , sleep maintenance efficiency index , and percentage of rapid eye movement sleep . Earplugs worn during exposure to the noise produced a significant decrease in rapid eye movement latency and an increase in the percentage of rapid eye movement sleep . CONCLUSION The results provide a reasonable basis for testing the effects of earplugs on the sleep of critically ill subjects Disturbed sleep and sleep deprivation is common in patients in critical care setting s. Noise and inappropriate use of light/dark cycles are two of the causes of sleep interruptions . The purpose of the study was to evaluate eye masks and earplugs to help control patients ' exposure to noise and light within the critical care environment . An intervention study using a two group post-test quasi-experimental design of high dependency patients within a cardiothoracic critical care unit was undertaken by a group of critical care nurses . Sleep assessment rating scales and open-ended questions were used to obtain patients ' reported experiences of their sleep . Patients self-selected into either an intervention or non-intervention group . Sixty-four patients consented to take part in the study , 34 patients tried the interventions earplugs and eye masks and many found they improved sleep . However , noise was still a factor preventing sleep for both groups of patients . Mixed reports were found with the interventions from very comfortable to very uncomfortable . At a cost of 2.50 pounds sterling/patient , earplugs and eye masks were a relatively cheap intervention with notable improvements for some critically ill patients . Further research is required with a larger sample size , plus an examination of both earplugs and eye masks separately . Offering patient 's earplugs and eye masks to improve sleep should be considered as a matter of routine nursing practice , this should include time to show patients how to use and try them out for comfort Background : Sleep is one of the basic human needs and sleep deprivation causes numerous undesirable effects on the human body and mind , especially in the intensive care unit ( ICU ) patients . It seems that noise and light are important environmental factors interrupting sleep in these patients . This study was carried out to determine the effect of earplugs and eye mask on Iranian patients ’ sleep quality in ICU . Material s and Methods : In this cross-over clinical trial , 50 patients in the ICUs of Al-zahra Medical Center in Isfahan in 2012 were selected by convenient sampling method and r and omly assigned to two groups . In group A , patients wore earplugs and eye mask in the first night during their sleep and slept without earplugs and eye mask in the second night , and the intervention was conversely conducted in group B. Verran and Snyder-Halpern Sleep Scales were used to measure the patients ’ sleep quality . The data were analyzed by paired t-test , independent t-test , one- sample t-test , and one-way analysis of variance ( ANOVA ) through SPSS version 18 . Results : Effect of the intervention on sleep effectiveness was positive , and there were significant differences ( P < 0.001 ) between treatment night and control night , and also within each group ( P < 0.001 ) . Effect of the interventions on sleep disturbance was positive , and there was a significant difference at treatment night compared to the control night between groups and within each group ( P < 0.001 ) . Also , the mean scores for sleep supplementation were measured after the second night , and the results showed the scores significantly increased in the intervention group compared to the control group ( P < 0.001 , ER = 47 , F = 22.1 ) . In addition , carryover effects for sleep efficiency and sleep disturbance were positive , but periodic effects for sleep efficiency and sleep disturbance were negative and positive , respectively . Conclusions : Although wearing earplugs and eye mask is a cost-effective and safe method and can improve perceived sleep quality in ICU patients , further research is needed to demonstrate the effect of this method INTRODUCTION Sleep is one of the basic human needs and sleep deprivation causes nu-merous adverse effects on the human body and mind . Due to reduced sleep quality in patients with acute coronary syndrome , this study was carried out to determine the effect of eye mask on sleep quality in patients with acute coronary syndrome . METHODS In this two-group controlled clinical trial , sixty patients with acute coronary syndrome in the coronary care units of Baqiyatallah Hospital in Tehran in 2010 were selected by purpose ful sampling method and r and omly allocated to two groups of case and control . In the case group , in the second night stay , the intervention of eye mask was done per night and by using the Petersburg 's sleep quality index ; sleep quality was evaluated during and at the end of hospitalization . Then data were analyzed by paired t-test , independent t-test , Spearman and Pearson 's correlation coefficient and SPSS software version 19 . RESULTS Total sleep quality score of the case group was significantly decreased after intervention ( 4.86 ± 1.88 ) from before intervention ( 10.46 ± 4.09 ) ( p < 0.000 ) . In addi-tion , total score of sleep quality after intervention in the case group ( 4.86 ± 1.88 ) was significant different from the control group ( 8.43 ± 1.97 ) ( p < 0.005 ) . CONCLUSION Using eye mask , as an economical and uncomplicated method , can improve sleep quality in patients with acute coronary syndrome in the coronary care units and can be used as an alternative method of treatment instead of drug therapy OBJECTIVES To describe sleep patterns in older adults living in assisted living facilities ( ALFs ) and to explore the relationship between sleep disturbance and quality of life , functional status , and depression over 6 months of follow-up . DESIGN Prospect i ve , observational cohort study . SETTING Eighteen ALFs in the Los Angeles area . PARTICIPANTS One hundred twenty-one ALF residents aged 65 and older ( mean age 85.3 , 86 % female , 88 % non-Hispanic white ) . MEASUREMENTS Data were collected at baseline and 3 and 6 months after enrollment . Data collected were demographics , physical and cognitive functioning , depression , quality of life , comorbidities , medications , and subjective ( i.e. , question naires ) and objective ( i.e. , 3 days and nights of wrist actigraphy ) measures of sleep . RESULTS Sixty-five percent of participants reported clinical ly significant sleep disturbance on the Pittsburgh Sleep Quality Index , and objective wrist actigraphy confirmed poor sleep quality . In regression analyses including sleep variables and other predictors , more self-reported sleep disturbance at baseline was associated with worse health-related quality of life ( Medical Outcomes Study 12-item Short Form Survey Mental Component Summary score ) and worse depressive symptoms five-item Geriatric Depression Scale at follow-up . Worse nighttime sleep ( according to actigraphy ) at baseline was associated with worse activities of daily living functioning and more depressive symptoms at follow-up . CONCLUSIONS Sleep disturbance is common in older ALF residents , and poor sleep is associated with declining functional status and quality of life and greater depression over 6 months of follow-up . Studies are needed to determine whether improving sleep in ALF residents will result in improvements in these outcomes . Well-established treatments should be adapted for use in ALFs and systematic ally evaluated in future research AIMS This study aim ed to determine the effects of earplug use on the subjective experience of sleep for patients in critical care . BACKGROUND The negative effects of noise in critical care include sleep disturbances , increased stress response , and reduced patient satisfaction . The nature of critical care often precludes quiet time protocol s. Previous studies indicated that earplugs can improve REM sleep and sleep efficiency . This study examined the effects of earplugs as a non-invasive method for improving the subjective sleep experience and increasing patient satisfaction . DESIGN Quasi-experimental intervention study with r and om assignment of subjects . METHOD Subjects were non-ventilated , non-se date d adults admitted to critical care . The intervention group used earplugs during nighttime sleep hours allowing short term removal during patient care . Participants completed the Verran-Snyder-Halpern Sleep Scale , an 8- question visual analogue scale , to describe their subjective response to sleep . Two sample T-tests were used to detect differences between the group scores . RESULTS 88 participants ( 49 intervention/39 control ) completed the study . Mean age 63 , 56 % males , 93 % Caucasian . Total sleep satisfaction scores were significantly better for the intervention group ( p = .002 ) . Seven of the subjective categories were independently significant ( p = .005-.044 ) . One category , satisfaction with the amount of time needed to fall asleep , was not significant ( p = .111 ) . CONCLUSIONS Earplug use improved the subjective experience of sleep for un-medicated critical care patients without interfering with care delivery . RELEVANCE TO PRACTICE The negligible cost and low level of invasiveness of earplugs makes this preferable as a primary intervention to promote sleep while avoiding unnecessary sedating medications |
573 | 15,717,035 | Results are mixed on whether educating physicians about evidence -based recommendations is sufficient to change physician behavior . | Summary Despite the availability of vast quantities of evidence from basic biomedical and clinical studies , a gap often exists between the optimal practice suggested by the evidence and actual practice .
For many clinical situations , however , evidence is unavailable , of poor quality or contradictory .
Out of necessity , clinicians have become accustomed to relying on non- evidence -based tools to make decisions .
Out of habit , they rely on these tools even when high- quality evidence becomes available .
Growing out of an increasing awareness of this problem , the evidence -based medicine ( EBM ) movement sought to empower clinicians to find the evidence most relevant to a specific clinical question .
Various organizations have used EBM techniques to develop systematic review s and practice guidelines to aid physicians in making evidence -based decisions .
Additionally , despite enormous research efforts there remains a lack of high- quality evidence to guide care for many clinical situations | Objective : To determine the effectiveness of steroids , acyclovir , and surgical facial nerve decompression in Bell ’s palsy . Methods : The authors identified articles by search ing MEDLINE and selected those that prospect ively compared outcomes in patients treated with steroids , acyclovir , or surgery with patients not receiving these modalities . The authors grade d the quality of each study ( class I to IV ) using a st and ard classification-of- evidence scheme . They compared the proportion of patients recovering facial function in the treated group to the proportion of patients recovering facial function in the control group . Results : The authors identified no adequately powered class I studies for any treatment modality . The pooled results of two class I and two class II studies showed significantly better facial outcomes in steroid-treated patients compared with non – steroid-treated patients ( relative rate good outcome 1.16 , 95 % CI 1.05 to 1.29 ) . One class II study demonstrated a significant benefit from acyclovir in combination with prednisone compared with prednisone alone ( relative rate good outcome 1.22 , 95 % CI 1.02 to 1.45 ) . All studies describing outcomes in patients treated with facial nerve decompression were grade d as class IV . Conclusion : For patients with Bell ’s palsy , a benefit from steroids , acyclovir , or facial nerve decompression has not been definitively established . However , available evidence suggests that steroids are probably effective and acyclovir ( combined with prednisone ) is possibly effective in improving facial functional outcomes . There is insufficient evidence to make recommendations regarding surgical facial nerve decompression for Bell ’s palsy . Well- design ed studies of the effectiveness of treatments for Bell ’s palsy are still needed A prospect i ve , controlled , double-blind study was design ed to evaluate the effect of steroid treatment on the natural history of Bell 's palsy . Fifty-one patients were included in the study between 1972 and 1974 . The patients were evaluated and started on treatment within two days of onset of Bell 's palsy and followed for six months . Treatment was given in r and omized double-blind fashion and consisted of either vitamins or a total of 410 mg of prednisone plus vitamins in descending doses over 10 days . The recovery of facial motor function was determined by three physicians who had no knowledge of the treatment received by the patients . They examined photographs of the patients taken six months after onset of paralysis in eight positions of facial function and categorized them as to complete fair , or poor recovery of facial function . These results of this evaluation were su bmi tted to the biostatistician who broke the treatment code . The results of this study demonstrate no statistically significant beneficial effect of steroid therapy upon recovery from Bell 's palsy . Factors considered included the patients ' age , sex , the presence of pain , ageusia , hyperacusis , diabetes , hypertension , the progression and degree of palsy , the results of nerve excitability and salivary flow tests , and the time at which recovery was first noted or became complete . Bell 's palsy remains without a proven efficacious treatment The Quality St and ards Subcommittee of the American Academy of Neurology is charged with developing practice parameters for neurologists for diagnostic procedures , treatment modalities , and clinical disorders . The selection of topics for which practice parameters are used is based on prevalence , frequency of use , economic impact , membership involvement , controversy , urgency , external constraints , and re sources required . This paper addresses the role of thymectomy in the treatment of nonthymomatous autoimmune MG . In 1939 , Blalock et al.1 reported the remission of generalized MG in a 21-year-old woman after removal of a cystic thymic tumor . Subsequently , Blalock et al.2,3 performed thymectomy on MG patients without thymoma , found hyperplasia in the thymus gl and s , and reported improvement in at least half of their patients . Since these reports , thymectomy , with or without the presence of thymoma , has gained widespread acceptance as a form of treatment for MG . Because a definitive study of the effectiveness of thymectomy has never been done,4,5 the role of thymectomy in the management of MG remains uncertain . Nevertheless , physicians have to advise their patients regarding the benefits of thymectomy based on the existing literature . Our goal is to develop evidence -based recommendations for clinicians considering thymectomy for patients with nonthymomatous autoimmune MG by performing a systematic review and analysis of the literature . # # # Identification and selection of studies . We search ed the National Library of Medicine ’s Medline data base from 1966 to February 1998 using the medical subject headings “ myasthenia gravis ” ( restricted to the surgery subheading ) and “ thymectomy . ” To identify articles published before 1966 , or missed by our original search strategy , we review ed the references of the identified articles . We classified the result ing articles into the following categories : Class II , controlled but nonr and omized studies describing outcomes in MG patients with and without thymectomy ; and Class III , uncontrolled case series describing outcomes in patients with or without Incomplete recovery from Bell 's palsy was observed in some patients even after the intake of corticosteroids . This prospect i ve study was performed on 160 patients with unilaterial nonrecurrent Bell 's palsy in order to investigate the role of prednisolone on the prognosis of Bell 's palsy . Ninety-three patients were given prednisolone tablets ( 1 mg/kg body wt/day up to 70 mg ) for six successive days , then the dose was reduced gradually over the next four days . The remaining 67 patients were not given prednisolone ( control group ) . Facial nerve recovery was assessed clinical ly and electrophysiologically for up to one year . The results of this study suggested that the most probable contributing factor for the success of prednisolone in improving the prognosis of Bell 's palsy was its early intake ( within the first 24 hours following onset ) |
574 | 27,864,184 | Conclusion : This meta- analysis of high- quality studies showed that surgical treatment of MCFs results in fewer nonunions , fewer malunions , and an accelerated return to work compared with nonsurgical treatment . | Background : There is no consensus on the choice of treatment of midshaft clavicle fractures ( MCFs ) .
Purpose : The aims of this systematic review and meta- analysis were ( 1 ) to compare fracture healing disorders and functional outcomes of surgical versus nonsurgical treatment of MCFs and ( 2 ) to compare effect estimates obtained from r and omized controlled trials ( RCTs ) and observational studies . | OBJECTIVES To evaluate the outcome and satisfaction of closed treatment versus open reduction and internal fixation in comminuted clavicular fractures . METHODS Sixty patients with displaced clavicular fractures were r and omized into operative ( 29 patients ) and nonoperative ( 31 patients ) groups . Three patients in the operative group did not accept the surgery , and seven patients in the nonoperative group did not complete the one-year follow-up . Outcomes were assessed using the Disability of the Arm , Shoulder and H and ( DASH ) score , Constant shoulder score , specific questions regarding patients ' final satisfaction , physical examination , measurement of the shortening of the clavicular length , and plain radiographs . RESULTS There was one nonunion in the operative group and one in the nonoperative group . The nonunion in operative group was the result of the only infection in this group . Four malunions were developed in the operative group and nineteen malunions in the nonoperative treatment , ( p<0.001 ) . Three patients in the operative group were completely dissatisfied with their treatment . Eighteen patients in the nonoperative group were partially satisfied . Pain was the main reason for dissatisfaction in this group . The mean shortening of the clavicle was 26.5 mm in the nonoperative group and 4.0 mm in the operative group . The mean DASH score for the operative and nonoperative groups were 8.6 and 21.3 , respectively ( p<0.001 ) ; and the Constant shoulder scores were 89.8 and 78.8 ( p<0.001 ) . CONCLUSION Open reduction and internal fixation of comminuted fractures of the clavicle using a reconstruction plate is an effective treatment modality . Despite the variety of complications , this method has a higher satisfaction rate than conservative treatment We conducted a prospect i ve , r and omized study to determine if patients with midshaft clavicle fractures would benefit from immediate operative stabilization with a modified Hagie pin in comparison with a matched group treated with nonoperative therapy . At a level II trauma center , patients with closed midshaft clavicle fractures were prospect ively r and omized to receive either operative or nonoperative treatment . Fifty-seven ( 29 operative , 28 nonoperative ) patients were enrolled in the study . Operative patients underwent open reduction and internal fixation of the clavicle using a modified Hagie pin ; nonoperative patients were treated with a sling for comfort . All patients were followed at regular intervals for 1 year . They were evaluated for radiographic healing and complications and were scored with the Single Assessment Numeric Evaluation and L'Insalata instruments . Injury severities and radiographs were not statistically significantly different between the 2 groups . Functional scores in the operative group were slightly higher at 3 weeks , and the nonoperative group had slightly higher scores at 6 months and 1 year . The only statistically significant difference between the groups was at 3 weeks . Percentage follow-up at 1 year was 93 % for the operative group and 82 % for the nonoperative group . One patient in each group developed a nonunion , and 1 patient in each group had a refracture . Complications were higher in the operative group , and most were related to pin prominence at the posterior shoulder . Results of this study suggest that , though patients with midshaft clavicle fractures had higher functional scores at short-term follow-up after internal fixation , functional scores were similar at 6 months and 1 year . In addition , internal fixation with a modified Hagie pin was associated with a higher complication rate Objectives : To determine the cost-effectiveness of open reduction internal fixation ( ORIF ) of displaced , midshaft clavicle fractures in adults . Design : Formal cost-effectiveness analysis based on a prospect i ve , r and omized , controlled trial . Setting : Eight hospitals in Canada ( seven university-affiliated and one community hospital ) . Patients / Participants : One hundred thirty-two adults with acute , completely displaced , midshaft clavicle fractures . Intervention : Clavicle ORIF versus nonoperative treatment . Main Outcome Measurements : Utilities derived from SF-6D . Results : The base case cost per quality -adjusted life-year ( QALY ) gained for ORIF was $ 65,000 . Cost-effectiveness improved to $ 28,150/QALY gained when the functional benefit from ORIF was assumed to be permanent with cost per QALY gained falling below $ 50,000 when the functional advantage persisted for 9.3 years or more . In other sensitivity analyses , the cost per QALY gained for ORIF fell below $ 50,000 when ORIF cost less than $ 10,465 ( base case cost $ 13,668 ) or the long-term utility difference between nonoperative treatment and ORIF was greater than 0.034 ( base case difference 0.014 ) . Short-term disutility associated with fracture healing also affected cost-effectiveness with the cost per QALY gained for ORIF falling below $ 50,000 when the utility of a fracture treated nonoperatively before union was less than 0.617 ( base case utility 0.706 ) or when nonoperative treatment increased the time to union by 20 weeks ( base case difference 12 weeks ) . Conclusions : The cost-effectiveness of ORIF after acute clavicle fracture depended on the durability of functional advantage for ORIF compared with nonoperative treatment . When functional benefits persisted for more than 9 years , ORIF had a favorable value compared with many accepted health interventions Background The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures . Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries . Aim A prospect i ve , multicentre r and omised controlled trial ( RCT ) will be conducted in 21 hospitals in the Netherl and s , comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation . Methods / design A total of 350 patients will be included , between 18 and 60 years of age , with a dislocated midshaft clavicular fracture . The primary outcome is the incidence of non-union , which will be determined with st and ardised X-rays ( Antero-Posterior and 30 degrees caudocephalad view ) . Secondary outcome will be the functional outcome , measured using the Constant Score . Strength of the shoulder muscles will be measured with a h and held dynamometer ( MicroFET2 ) . Furthermore , the health-related Quality of Life score ( ShortForm-36 ) and the Disabilities of Arm , Shoulder and H and ( DASH ) Outcome Measure will be monitored as subjective parameters . Data on complications , bone union , cosmetic aspects and use of painkillers will be collected with follow-up question naires . The follow-up time will be two years . All patients will be monitored at regular intervals over the subsequent twelve months ( two and six weeks , three months and one year ) . After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes . All data will be analysed on an intention-to-treat basis , using univariate and multivariate analyses . Discussion This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two st and ardised treatment options for dislocated midshaft clavicular fractures . The gathered data may support the development of a clinical guideline for treatment of clavicular fractures . Trial registration Netherl and s National Trial Register INTRODUCTION Elastic stable intramedullary nailing ( ESIN ) of displaced mid-shaft clavicular fractures is a minimally invasive technique which was reported to be an easy procedure with low complication rates , good cosmetic and functional results , restoration of clavicular length and fast return to daily activities . Recent studies , however , also report on higher complication rates and specific problems with the use of this technique . This prospect i ve study compares ESIN with non-operative treatment of displaced mid-shaft clavicular fractures . METHODS Between December 2003 and August 2007 , 120 patients volunteered to participate . Of these , 112 patients completed the study ( 60 in the operative and 52 in the non-operative group ) . Patients in the non-operative group were treated with a simple shoulder sling . In the operative group , intramedullary stabilisation was performed within 3 days of the trauma . Clavicular shortening was determined after trauma and after osseous consolidation on thorax posteroanterior radiographs as the proportional length difference between the left and right side with the uninjured side serving as a control for clavicular length ( 100 % ) . Radiographic union was assessed every 4 weeks on 20 degrees cephalad anteroposterior and posteroanterior radiographs of the clavicle . Constant shoulder scores and DASH scores ( DASH , disabilities of the arm , shoulder and h and ) were assessed at final follow-up after 2 years . RESULTS ESIN led to faster osseous healing and better restoration of clavicular length in simple fractures . We were not able to restore clavicular length in comminuted fractures using ESIN . Functional outcome at a mean follow-up of 24 months ( range : 22 - 27 months ) was better in the operative group . Delayed union and non-union accounted for the majority of complications in the non-operative group . In the operative group , telescoping was the main complication , which occurred in complex fractures with severe post-traumatic shortening only . CONCLUSION We recommend ESIN for all simple displaced mid-shaft clavicular fractures in order to minimise the rate of delayed union , non-union and symptomatic mal-union . We also recommend ESIN in comminuted fractures with moderate ( < or = 7 % ) post-traumatic shortening , as they will heal with moderate shortening . In comminuted fractures with severe shortening , however , we recommend plate osteo synthesis in order to provide for stability , clavicular length and endosteal blood supply BACKGROUND Clavicle fractures are common and usually heal without complications . In this study , we evaluated the outcomes of non-operative versus operative management of displaced fractures . METHODS In a prospect i ve clinical trial study , sixty-five patients with displaced clavicle mid-shaft fractures were non-r and omly divided in two treatment groups . The first group underwent non-operative treatment with figure of 8 b and age ( 30 patients ) , and the other underwent operative treatment with plate fixation ( 35 patients ) . Figure of 8 b and age and 3.5 millimeter DCP plate with at least six cortical screws were used in non-operative and operative groups respectively . We followed up all patients at weeks 2 , 6 and 12 , and at month sixth . In addition to clinical examination and x-ray evaluation , we assessed satisfaction , DASH and Constant Shoulder Score for each individual . RESULTS The average duration s of union were 19.3 and 24.4 weeks in operative and non-operative groups respectively ( P=0.006 ) . Satisfaction with operative treatment was 74.3 % and with non-operative treatment was 66.7 % , showing no significant difference ( P=0.500 ) . The non-union rate was 5.7 % in the operative group and 13.3 % in the non-operative group ( P=0.518 ) . A significant difference between the two groups in terms of DASH and Constant Shoulder Scores after the six-month follow-up was not found ( P=0.352 ) . CONCLUSIONS According to our results , we recommend operative treatment in mid-shaft clavicle fractures only when there is a definitive indication Objectives : To compare results of primary internal fixation of acute displaced midshaft clavicle fractures with those managed nonoperatively in terms of fracture union and functional outcome . Design : Prospect i ve cohort study . Setting : Level II military trauma center . Patients / Participants : Seventy-three patients ( civilian and military ) between 20 and 50 years of age with displaced midshaft clavicle fractures were allocated either to the operative ( n = 45 ) or nonoperative ( n = 28 ) group . Intervention : Patients in the nonoperative group were managed by simple sling immobilization , whereas in the operative group , fractures were reduced and fixed with a contoured reconstruction plate . Main Outcome Measurements : The patients were actively followed up during an 18-month period . Primary outcome measures were the rates of nonunion and symptomatic malunion ; secondary outcomes included the assessment of the Constant score and the overall local complication rate . Results : The 18-month follow-up rate was 90 % . All fractures in the operative group united compared with eight nonunions ( 29 % ) in the nonoperative group ( P = 0.002 ) . Ten symptomatic malunions ( 36 % ) occurred in the nonoperative group , whereas only two ( 4 % ) were reported for the operative group ( P = 0.0008 ) . Constant shoulder scores were significantly better for the operative group at all follow-ups ( P < 0.0001 ) . All six operative complications were implant-related . Conclusions : In this prospect i ve cohort study , primary open reduction and internal plate fixation of acute displaced midshaft clavicular fractures result ed in improved outcomes and a decreased rate of nonunion and symptomatic malunion compared with nonoperative treatment BACKGROUND Surgical treatment with open reduction and internal fixation ( ORIF ) of displaced middle-third clavicular fractures result ed in shorter complete return to work periods with earlier consolidation documented on computed tomography ( CT ) scans in this prospect i ve , r and omized controlled trial . METHODS The study r and omized 76 consecutive patients with displaced fractures ( 2B1 - 2B2 according to Robinson ) to conservative ( C , n = 42 ) and surgical ( S , n = 34 ) treatment with plates and screws . Bone union was documented with CT scans at 6 and 12 weeks . RESULTS Risk factors known to increase the risk of nonunion were similar between groups . Time until discharge for complete return to work was 3.7 ± 1.1 months for C and 2.9 ± 0.8 months for S ( P = .003 ) . On the CT scan at 6 weeks , 24.1 % of the patients presented advanced bone union in S vs 5.3 % in C ( P = .05 ) . At 12 weeks , 81 % of the patients presented advanced bone union in S vs 16.7 % in C ( P = .005 ) . At final follow-up , 4 nonunions were present in the C group that required surgery ; in the S group , 4 patients underwent revision surgery for plate removal . At 6 and 12 months of follow-up , Constant scores were higher for the S group . CONCLUSIONS Surgical treatment with ORIF of displaced middle-third clavicular fractures achieved good and excellent functional results , shorter time to complete return to work , earlier bone union , and fewer cases of nonunions in a working population under injury compensation Objective : To compare elastic stable intramedullary nailing ( ESIN ) with nonoperative treatment of fully displaced midshaft clavicular fractures in adults . Design : The study was a r and omized , controlled , clinical trial . Setting : Level 1 trauma center . Patients and Methods : Sixty patients between 18 and 65 years of age participated and completed the study . They were r and omized to either operative or nonoperative treatment with a 2-year follow-up . Intervention : Thirty patients were treated with a simple shoulder sling and 30 patients with ESIN within 3 days after trauma . Main Outcome Measurement : Complications after operative and nonoperative treatments , Disabilities of the Arm , Shoulder and H and ( DASH ) score and Constant Shoulder Score for outcome measurement , and clavicular shortening . Results : Fracture union was achieved in all patients in the operative group , whereas nonunion was observed in 3 of 30 patients of the nonoperative group . Two symptomatic malunions required corrective osteotomy in the nonoperative group . Medial nail protrusion occurred in 7 cases in the operative group . Implant failure with revision surgery was necessary in 2 patients after an additional adequate trauma . DASH scores were lower in the operative group throughout the first 6 months and 2 years after trauma , with a significant difference during the first 18 weeks . Constant scores were significantly higher after 6 months and 2 years after intramedullary stabilization . Patients in the operative group showed a significant improvement of posttraumatic clavicular shortening ; they were also more satisfied with cosmetic appearance and overall outcome . Conclusions : ESIN of displaced midshaft clavicular fractures result ed in a lower rate of nonunion and delayed union , a faster return to daily activities , and a better functional outcome . Clavicular shortening was significantly lower , and overall satisfaction was higher in the operative group AIM In Germany , non-operative treatment using a figure of eight dressing is the most common method for managing fractures of the mid-third of the clavicle . This treatment is chosen preferably even in cases of dislocated fractures . The described procedures of open osteo synthesis are characterised by a huge access trauma . Up to date literature shows the advantages of intramedullary pin osteo synthesis , which can be considered as a minimally invasive procedure . In this study we compare the results of pin-osteo synthesis with the non-operative treatment in athletes . METHODS This prospect i ve r and omised trial compares the results of 68 athletes with an isolated fracture of the middle third of the clavicle . One group ( n=35 ) received intramedullary splints , the other group ( n=33 ) had a figure of eight dressing instead . RESULTS Post-traumatic pain was significantly ( p=0.05 ) lower in the group that had intramedullary splints . Furthermore , the postoperative mobility of the injured area was significantly better ( p=0.05 ) . Measurements of the strength of the injured side 120 days after the trauma show a significant ( p=0.01 ) advantage of the pin osteo synthesis . CONCLUSION The intramedullary titanium pin osteo synthesis is a promising alternative with better results . Up to date literature and our own results prove the advantages of this minimally invasive osteo synthesis . This procedure allows sports activities to be resumed soon after the operation . As intramedullary pin osteo synthesis is an ideal operation of fractures of the middle third of the clavicle , this comparatively easy procedure with few complications should be more widespread BACKGROUND There is a growing trend to treat displaced midshaft clavicular fractures with primary open reduction and plate fixation ; whether such treatment results in improved patient outcomes is debatable . The aim of this multicenter , single-blinded , r and omized controlled trial was to compare union rates , functional outcomes , and economic costs for displaced midshaft clavicular fractures that were treated with either primary open reduction and plate fixation or nonoperative treatment . METHODS In a prospect i ve , multicenter , stratified , r and omized controlled trial , 200 patients between sixteen and sixty years of age who had an acute displaced midshaft clavicular fracture were r and omized to receive either primary open reduction and plate fixation or nonoperative treatment . Functional assessment was conducted at six weeks , three months , six months , and one year with use of the Disabilities of the Arm , Shoulder and H and ( DASH ) and Constant scores . Union was evaluated with use of three-dimensional computed tomography . Complications were recorded , and an economic evaluation was performed . RESULTS The rate of nonunion was significantly reduced after open reduction and plate fixation ( one nonunion ) as compared with nonoperative treatment ( sixteen nonunions ) ( relative risk = 0.07 ; p = 0.007 ) . Group allocation to nonoperative treatment was independently predictive of the development of nonunion ( p = 0.0001 ) . Overall , DASH and Constant scores were significantly better after open reduction and plate fixation than after nonoperative treatment at the time of the one-year follow-up ( DASH score , 3.4 versus 6.1 [ p = 0.04 ] ; Constant score , 92.0 versus 87.8 [ p = 0.01 ] ) . However , when patients with nonunion were excluded from analysis , there were no significant differences in the Constant scores or DASH scores at any time point . Patients were less dissatisfied with symptoms of shoulder droop , local bump at the fracture site , and shoulder asymmetry in the open reduction and plate fixation group ( p < 0.0001 ) . The cost of treatment was significantly greater after open reduction and plate fixation ( p < 0.0001 ) . CONCLUSIONS Open reduction and plate fixation reduces the rate of nonunion after acute displaced midshaft clavicular fracture compared with nonoperative treatment and is associated with better functional outcomes . However , the improved outcomes appear to result from the prevention of nonunion by open reduction and plate fixation . Open reduction and plate fixation is more expensive and is associated with implant-related complications that are not seen in association with nonoperative treatment . The results of the present study do not support routine primary open reduction and plate fixation for the treatment of displaced midshaft clavicular fractures INTRODUCTION The aim of the present prospect i ve clinical trial was to compare patient-oriented and surgeon-based outcomes after non-operative care with operative treatment of displaced midshaft clavicle fractures . PATIENTS / METHODS Between January 2009 and July 2011 , 97 consecutive patients presenting with a midshaft clavicle fracture were prospect ively recorded and included in this study . The patients were placed in either of the treatment groups on their own preference . They were then seen in outpatient clinic at two , six and 24 weeks were all endpoints were investigated and motivation of choice of treatment was noted . Study follow-up was continued until Augustus 2014 , being the time point that long-term functional outcome was measured through a DASH score by letter . RESULTS 97 patients were included in the functional outcome analysis . The mean DASH and Constant scores were significant better in the operative ( 90.9±14.2 and 15.7±17.2 ) than in the conservative treatment group at six weeks ( 78.7±17.0 and 24.8±16.7 ) . There was a significant improvement in the Constant ( 95.9±10.5 versus 94.5±5.9 ) and DASH scores ( 8.8±12.0 versus 7.1±10.7 ) for both groups at 24 weeks but there was no significant difference in functional scores between the groups . Four patients developed a non-union , one patient in the operative and three patients in the conservative group . Overall complications were significantly higher in the operative group ( 31 % ) compared to the conservative group ( 9 % ) ( p<0.001 ) . There was no significant difference in long-term functional outcome between the two treatment groups ( 5.2±9.8 versus 2.5±4.9 p=0.12 ) . Patient 's satisfaction was higher in the operative than in the conservative group ( p<0.04 ) . CONCLUSION Significant superior outcome scores were seen at six weeks for the operative group . However , at 24 weeks and 5-year follow-up no difference was seen in functional outcome scores for both treatment groups . Therefore , the challenge for the future is to better identify the subgroup of patients who might benefit from primary surgical intervention OBJECTIVE Studies showed elastic stable intramedullary nailing ( ESIN ) of displaced midclavicular fractures has excellent outcomes , as well as high complication rates and specific problems . The aim was to discuss ESIN of midshaft clavicular fractures . METHODS Totally 60 eligible patients ( aged 18 - 63 years ) were r and omized to either ESIN group or non-operative group between January 2007 and May 2008 . Clavicular shortening was measured after trauma and osseous consolidation . Radiographic union and complications were assessed . Function analysis including Constant shoulder scores and disabilities of the arm , shoulder and h and ( DASH ) scores were performed after a 15-month follow-up . RESULTS ESIN led to a signifcantly shorter time to union , especially for simple fractures . In ESIN group , all patients got fracture union , of which 5 cases had medial skin irritation and 1 patient needed revision surgery because of implant failure . In the nonoperative group , there were 3 nonunion cases and 2 symptomatic malunions developed requiring corrective osteotomy . At 15 months after intramedullary stabilization , patients in the ESIN group were more satisfied with the appearance of the shoulder and overall outcome , and they benefited a lot from the great improvement of post-traumatic clavicular shortening . Furthermore , DASH scores were lower and Constant scores were significantly higher in contrast to the non-operative group . CONCLUSION ESIN is a safe minimally invasive surgical technique with lower complication rate , faster return to daily activities , excellent cosmetic and better functional results , restoration of clavicular length for treating mid-shaft clavicular fractures , result ing in high overall satisfaction , which can be regard as an alternative to plate fixation or nonoperative treatment of mid-shaft clavicular fractures The choice of treatment for midshaft clavicular fractures is not straightforward , but depends on fracture characteristics such as comminution , angulation and displacement . An online survey was conducted amongst trauma and orthopaedic surgeons to determine the preferred treatment for midshaft clavicular fractures , based on anteroposterior radiographs , for 17 r and omly selected displaced or comminuted midshaft clavicular fractures . The background and experience of the respondents were documented . Data were analyzed using a Generalized Estimating Equations ( GEE ) model . The 102 respondents preferred non-operative treatment more frequently for displaced fractures than for comminuted fractures ( OR 3.24 , 95 % CI 2.55 - 4.12 ) . Locking plate fixation was more often preferred over other surgical modalities for comminuted than for displaced fractures ( OR 1.50 , 95 % CI 1.17 - 1.91 ) . In clinical practice , there is no consensus between surgeons on the choice of treatment for displaced or comminuted midshaft clavicular fractures . This lack of agreement calls for evidence -based treatment guidelines for these fractures |
575 | 23,684,373 | These findings suggest a statistically significant increase in the risk of hyperglycemia , hypercholesterolemia ( all grade s and grade 3 and 4 ) , and all grade hypertriglyceridemia associated with mTOR therapy when compared with control .
INTERPRETATION The risk of all grade and grade 3 - 4 , hyperglycemia , hypercholesterolemia , and hypertriglyceridemia , are increase in patients treated with mTOR inhibitors compared with control | BACKGROUND mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies .
The risk of metabolic complications with these agents is not well characterized . | Background The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin ( mTOR ) kinase is an important mediator for its signaling . Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3 K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells ( negative feedback loop ) . The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in pre clinical tumor models . Methods Two studies prospect ively enrolled adult patients with advanced pancreatic cancer , Eastern Cooperative Oncology Group performance status 0 - 1 , adequate hematologic , hepatic and renal parameters and measurable disease . In Study A , temsirolimus was administered intravenously at 25 mg weekly . In Study B , everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily . The primary endpoint in both studies was overall survival at 6 months . Secondary endpoints included time to progression , progression-free survival , overall survival , response rate , safety and toxicity . Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR , pAkt/Akt , pErk/Erk , pS6 , p4EBP-1 and PTEN . Results Five patients enrolled in Study A ; Two patients died within a month ( rapid disease progression and hemorrhagic stroke , respectively ) . One patient developed dehydration and another developed asthenia . Sixteen patients enrolled in Study B. : 12 males , all ECOG PS = 1 . Median cycles = 1 ( range 1 - 2 ) . Grade 4 toxicity : hyponatremia ( n = 1 ) , Grade 3 : diarrhea ( n = 1 ) , cholangitis ( n = 3 ) , hyperglycemia ( n = 1 ) , fatigue ( n = 1 ) . Grade 2 : pneumonia ( n = 2 ) , dehydration ( n = 2 ) , nausea ( n = 2 ) , neutropenia ( n = 1 ) , mucositis ( n = 2 ) & rash ( n = 2 ) . Four patients were hospitalized . Progressive disease occurred in 15 and 1 was non-evaluable . Pretreatment biopsies revealed a higher pAkt/Akt ratio in tumor specimens that in nonmalignant pancreatic tissue . No such trends were noted for the other biomarkers . Conclusions Neither study with mTOR inhibitors demonstrated objective responses or disease stability . The negative feedback loop result ing from mTOR inhibition may account for the disease progression and toxicity noted in these studies . Future strategies should aim for a broader targeting of the PI3 K pathway in pancreatic cancer . Trial Registration Trial registration : Study A : NCT 0075647 . Study B : Purpose : Loss of PTEN , which is common in glioblastoma multiforme ( GBM ) , results in activation of the mammalian target of rapapmycin ( mTOR ) , thereby increasing mRNA translation of a number of key proteins required for cell-cycle progression . CCI-779 is an inhibitor of mTOR . The primary objectives of this study were to determine the efficacy of CCI-779 in patients with recurrent GBM and to further assess the toxicity of the drug . Experimental Design : CCI-779 was administered weekly at a dose of 250 mg intravenously for patients on enzyme-inducing anti-epileptic drugs ( EIAEDs ) . Patients not on EIAEDs were initially treated at 250 mg ; however , the dose was reduced to 170 mg because of intolerable side effects . Treatment was continued until unacceptable toxicity , tumor progression , or patient withdrawal . The primary endpoint was 6-month progression-free survival . Results : Forty-three patients were enrolled ; 29 were not on EIAEDs . The expected toxicity profile of increased lipids , lymphopenia , and stomatitis was seen . There were no grade IV hematological toxicities and no toxic deaths . One patient was progression free at 6 months . Of the patients assessable for response , there were 2 partial responses and 20 with stabilization of disease . The median time to progression was 9 weeks . Conclusions : CCI-779 was well tolerated at this dose schedule ; however , there was no evidence of efficacy in patients with recurrent GBM . Despite initial disease stabilization in approximately 50 % of patients , the durability of response was short . Because of the low toxicity profile , CCI-779 may merit exploration in combination with other modalities St and ard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity . A phase II study was design ed to evaluate the efficacy , safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma ( NEC ) . Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus . Patients were evaluated for tumour response , time to progression ( TTP ) , overall survival ( OS ) and adverse events ( AE ) . Twenty-two archival specimens , as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers . The intent-to-treat response rate was 5.6 % ( 95 % CI 0.6–18.7 % ) , median TTP 6 months and 1-year OS rate 71.5 % . The most frequent drug-related AE of all grade s as percentage of patients were : fatigue ( 78 % ) , hyperglycaemia ( 69 % ) and rash/desquamation ( 64 % ) . Temsirolimus effectively inhibited the phosphorylation of S6 ( P=0.02 ) . Higher baseline levels of pmTOR ( phosphorylated mammalian target of rapamycin ) ( P=0.01 ) predicted for a better response . Increases in pAKT ( P=0.041 ) and decreases in pmTOR ( P=0.048 ) after treatment were associated with an increased TTP . Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC . Pharmacodynamic analysis revealed effective mTOR pathway downregulation Hypothesis : To study the progression-free survival ( PFS ) and toxicity with 25- or 250-mg doses of temsirolimus ( CCI-779 ) after induction chemotherapy in patients with extensive small-cell lung cancer . Methods : Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were r and omized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression . Results : Eighty-seven patients entered between January 2002 and December 2003 , of whom 85 were eligible : 44 received 25 mg ( arm A ) , and 41 received 250 mg ( arm B ) . The overall median follow-up time for all eligible patients was 34.6 months . Median age was 59 years ( range , 39–80 ) ; 42 ( 49.4 % ) were male and 43 ( 50.6 % ) female ; 12.9 % had brain metastases . The overall median and 1-year PFS were 2.2 months ( 95 % confidence interval [ CI ] : 1.8 , 2.9 ) and 4.7 % ( 95 % CI : 0.2 % , 9.2 % ) , respectively . The median PFS ( 95 % CI ) for arm A was 1.9 months ( 1.6 , 2.3 ) ; for arm B , it was 2.5 months ( 1.9 , 3.4 ; p = 0.24 ) . The median overall survival from r and omization was 8 months ( 95 % CI : 6.5 , 9.5 ) . Among the 86 patients with reported toxicities , 36 ( 42 % ) had grade 3 toxicities , the most common of which were thrombocytopenia , hypophosphatemia , and fatigue , and an additional 12 ( 14 % ) had grade 4 toxicities , the most common of which was neutropenia . No patients experienced lethal toxicities . Conclusion : Temsirolimus ( CCI 779 ) , given at 25 or 250 mg weekly , seemed not to increase the PFS in this patient population BACKGROUND Temsirolimus ( CCI-779 ) is a small-molecule inhibitor of the mammalian target of rapamycin ( mTOR ) and represents a rational therapeutic target against glioblastoma multiforme ( GBM ) . METHODS Recurrent GBM patients with < or = 1 chemotherapy regimen for progressive disease were eligible . Temsirolimus was administered in a 250-mg intravenous dose weekly . RESULTS Sixty-five patients were treated . The incidence of grade 3 or higher nonhematologic toxicity was 51 % , and consisted mostly of hypercholesterolemia ( 11 % ) , hypertriglyceridemia ( 8 % ) , and hyperglycemia ( 8 % ) . Grade 3 hematologic toxicity was observed in 11 % of patients . Temsirolimus peak concentration ( Cmax ) , and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme-inducing anticonvulsants ( EIACs ) by 73 % , 47 % , and 50 % , respectively , but were still within the therapeutic range of pre clinical models . Twenty patients ( 36 % ) had evidence of improvement in neuroimaging , consisting of decrease in T2 signal abnormality + /- decrease in T1 gadolinium enhancement , on stable or reduced steroid doses . Progression-free survival at 6 months was 7.8 % and median overall survival was 4.4 months . Median time to progression ( TTP ) for all patients was 2.3 months and was significantly longer for responders ( 5.4 months ) versus nonresponders ( 1.9 months ) . Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response ( 71 % v 31 % ; P = .04 ) . Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor sample s ( P = .04 ) . CONCLUSION Temsirolimus is well tolerated in recurrent GBM patients . Despite the effect of EIACs on temsirolimus metabolism , therapeutic levels were achieved . Radiographic improvement was observed in 36 % of temsirolimus-treated patients , and was associated with significantly longer TTP . High levels of phosphorylated p70s6 kinase in baseline tumor sample s appear to predict a patient population more likely to derive benefit from treatment . These findings should be vali date d in other studies of mTOR inhibitors PURPOSE Cross-talk between the estrogen receptor ( ER ) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin ( mTOR ) pathways is a mechanism of resistance to endocrine therapy , and blockade of both pathways enhances antitumor activity in pre clinical models . This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor , everolimus ( RAD001 ) . PATIENTS AND METHODS Two hundred seventy postmenopausal women with operable ER-positive breast cancer were r and omly assigned to receive 4 months of neoadjuvant treatment with letrozole ( 2.5 mg/day ) and either everolimus ( 10 mg/day ) or placebo . The primary end point was clinical response by palpation . M and atory biopsies were obtained at baseline and after 2 weeks of treatment ( ie , day 15 ) . Sample s were assessed for PI3 K mutation status ( PIK3CA ) and for pharmacodynamic changes of Ki67 , phospho-S6 , cyclin D1 , and progesterone receptor ( PgR ) by immunohistochemistry . RESULTS Response rate by clinical palpation in the everolimus arm was higher than that with letrozole alone ( ie , placebo ; 68.1 % v 59.1 % ) , which was statistically significant at the preplanned , one-sided , alpha = 0.1 level ( P = .062 ) . Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms , and dramatic downregulation of phospho-S6 occurred only in the everolimus arm . An antiproliferative response , as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15 , occurred in 52 ( 57 % ) of 91 patients in the everolimus arm and in 25 ( 30 % ) of 82 patients in the placebo arm ( P < .01 ) . The safety profile was consistent with historical results of everolimus monotherapy ; grade s 3 to 4 adverse events occurred in 22.6 % of patients who received everolimus and in 3.8 % of patients who received placebo . CONCLUSION Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) The primary goal of this trial was to evaluate the confirmed response rate of temsirolimus ( CCI‐779 ) , a mammalian target of rapamycin in patients with advanced soft tissue sarcomas ( STS ) PURPOSE To evaluate the efficacy , safety , and pharmacokinetics of multiple doses of CCI-779 , a novel mammalian target of rapamycin kinase inhibitor , in patients with advanced refractory renal cell carcinoma ( RCC ) . PATIENTS AND METHODS Patients ( n = 111 ) were r and omly assigned to receive 25 , 75 , or 250 mg CCI-779 weekly as a 30-minute intravenous infusion . Patients were evaluated for tumor response , time to tumor progression , survival , and adverse events . Blood sample s were collected to determine CCI-779 pharmacokinetics . RESULTS CCI-779 produced an objective response rate of 7 % ( one complete response and seven partial responses ) and minor responses in 26 % of these advanced RCC patients . Median time to tumor progression was 5.8 months and median survival was 15.0 months . The most frequently occurring CCI-779-related adverse events of all grade s were maculopapular rash ( 76 % ) , mucositis ( 70 % ) , asthenia ( 50 % ) , and nausea ( 43 % ) . The most frequently occurring grade 3 or 4 adverse events were hyperglycemia ( 17 % ) , hypophosphatemia ( 13 % ) , anemia ( 9 % ) , and hypertriglyceridemia ( 6 % ) . Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level . Patients were retrospectively classified into good- , intermediate- , or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa . Within each risk group , the median survivals of patients at each dose level were similar . CONCLUSION In patients with advanced RCC , CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested PURPOSE Ridaforolimus is an inhibitor of mammalian target of rapamycin , an integral component of the phosphatidyl 3-kinase/AKT signaling pathway , with early evidence of activity in sarcomas . This multicenter , open-label , single-arm , phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas . PATIENTS AND METHODS Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks . The primary end point was clinical benefit response ( CBR ) rate ( complete response or partial response [ PR ] or stable disease ≥ 16 weeks ) . Safety , progression-free survival ( PFS ) , overall survival ( OS ) , time to progression , and duration of response were also evaluated . RESULTS A total of 212 patients were treated in four separate histologic cohorts . In this heavily pretreated population , 61 patients ( 28.8 % ) achieved CBR . Median PFS was 15.3 weeks ; median OS was 40 weeks . Response Evaluation Criteria in Solid Tumors ( RECIST ) confirmed response rate was 1.9 % , with four patients achieving confirmed PR ( two with osteosarcoma , one with spindle cell sarcoma , and one with malignant fibrous histiocytoma ) . Archival tumor protein markers analyzed were not correlated with CBR . Related adverse events were generally mild or moderate and consisted primarily of stomatitis , mucosal inflammation , mouth ulceration , rash , and fatigue . CONCLUSION Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics . A phase III trial based on these data will further define ridaforolimus activity in sarcomas Dysregulation of phosphatase and tensin homolog ( PTEN ) and the gene that encodes the p110α catalytic subunit of phosphatidylinositol‐3‐kinase ( PI3 K ) , PIK3CA , are the most common mutations in endometrial carcinoma ( EC ) . Loss of PTEN or activation of PIK3CA results in constitutive activation of AKT , which leads to up‐regulation of mammalian target of rapamycin ( mTOR ) . Everolimus is an oral rapamycin analog that acts by selectively inhibiting mTOR Purpose : Mammalian target of rapamycin ( mTOR ) is a promising target in small cell lung cancer ( SCLC ) . We design ed a phase II study of everolimus , an mTOR inhibitor , in previously treated , relapsed SCLC . Experimental Design : Patients were treated with everolimus 10 mg orally daily until disease progression . The primary endpoint was disease control rate ( DCR ) at 6 weeks . PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue . Results : A total of 40 patients were treated : 23 had 1 prior regimen/sensitive relapse , 4 had 1 prior regimen/refractory , and 13 had 2 prior regimens . Twenty-eight patients received 2 or more cycles of everolimus , 7 received 1 cycle , and 5 did not complete the first cycle . Best response in 35 evaluable patients : 1 ( 3 % ) partial response ( in sensitive relapse ) , 8 ( 23 % ) stable disease , and 26 ( 74 % ) progression ; DCR at 6 weeks was 26 % ( 95 % CI = 11–40 ) . Median survival was 6.7 months and median time to progression was 1.3 months . Grade 3 toxicities included thrombocytopenia ( n = 2 ) , neutropenia ( n = 2 ) , infection ( n = 2 ) , pneumonitis ( n = 1 ) , fatigue ( n = 1 ) , elevated transaminases ( n = 1 ) , diarrhea ( n = 2 ) , and acute renal failure ( n = 1 ) . High phosphorylated AKT expression was modestly associated with overall survival ( HR = 2.07 ; 95 % CI = 0.97–4.43 ) . Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression ( P = 0.0093 ) . Conclusions : Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC . Further evaluation in combination regimens for patients with sensitive relapse may be considered . Clin Cancer Res ; 16(23 ) ; 5900–7 . © 2010 AACR |
576 | 15,830,140 | No significant differences were found for drainage volume or hospital stay .
Conclusion Current evidence from RCTs supports the use of a delayed program of arm exercises to reduce seroma formation .
Clinical and statistical inconsistencies between studies did not allow any conclusions to be drawn regarding the effects of delayed exercises on fluid drainage , hospital stay and immediate or long term ability to move the arm | Summary Background Seroma formation , wound healing and fluid drainage are a concern for both surgeons and patients .
Excessive fluid production can result in seroma formation , and inadequate drainage of seromas is known to cause infection , pain , discomfort and longer periods of hospitalisation .
Postoperative exercises given to maintain movement of the arm are believed to increase the amount of fluid production following surgery .
This review aim ed to determine whether a program of delayed exercises reduces the risk of seroma formation , fluid loss and hospital stay , without loss of arm movement . | 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 Abstract Background : Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer . Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction . The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced , without increasing shoulder dysfunction , by delayed postoperative shoulder exercises . Methods : In a prospect i ve study 163 patients with breast cancer undergoing modified radical mastectomy were r and omized to physiotherapy starting on postoperative day 1 or day 7 . Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department . Seromas and other complications were registered by the surgeons . The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function . Results : There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 ( 38 % ) compared to the group that started physiotherapy postoperative day 7 ( 22 % ) ( p<0.05 ) . There was no significant difference between the groups in the late outcome of shoulder function . Conclusion : The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively . Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function The role and timing of physical therapy following axillary dissection for melanoma , or in conjunction with modified radical mastectomy has not been extensively studied . A prospect i ve r and omized clinical trial was carried out over an 18-month period in the Surgery Branch , National Cancer Institute ( NCI ) and Department of Rehabilitation Medicine , Clinical Center , in which patients were assigned to receive one of two post-operative physical therapy regimens . Patients were assigned to receive graduated increases in allowed range of motion ( ROM ) , either beginning on postoperative day 1 ( early ) or day 7 ( delayed ) . All patients were advanced to full pain-free ROM when the suction catheters were removed . A total of 36 patients with 40 axillary dissections ( 19 for melanoma , 21 for breast cancer ) were included in this study . Patients r and omized to receive early motion had more total wound drainage ( 805 ± 516 cc vs. 420 ± 301 cc , p < 0.01 ) , more days of drainage ( 10.3 ± 5.3 vs. 6.2 ± 2.7 , p < 0.01 ) , and later postoperative day of discharge ( 12.8 ± 5.1 days vs. 9.2 ± 4.0 days , p < 0.02 ) than did patients who started motion on day 7 . Wound complications including infection and small areas of skin breakdown occurred more frequently in the early group ( seven patients vs. one patient , p < 0.02 ) . No significant differences in the per cent of patients achieving functional ROM could be identified between these two groups at one , three or six months after operation . Transient serratus anterior palsy ( 12 patients ) and latissimus dorsi palsy ( 2 patients ) occurred in approximately 30 % of all patients , regardless of group ( breast vs. melanoma , early vs. delayed ) , but returned to normal in all patients . The early institution of flexion and abduction exercises following axillary dissection thus appears to have a deleterious effect on wound healing and drainage . Adequate functional ROM is attained in all patients with a minimum of complications when active motion exercises are delayed for up to 7 days after axillary dissection A prospect i ve clinical trial was conducted to determine the effect of axillary node dissection for breast carcinoma on shoulder function and seroma production . 59 Operations were carried out in 57 patients . The patients were divided into two groups . In group A , shoulder exercises were started , under the guidance of a physiotherapist , immediately following surgery , and in group B the exercises were begun on the seventh postoperative day . A full range of motion within six months was achieved in 25 patients of group A ( 81 % ) and in 22 of group B ( 79 % ) . There was no significant difference in wound drainage between the two groups . Restricted shoulder movement was often seen after local wound complications following axillary radiotherapy or after seriously disturbed wound healing A r and omized prospect i ve clinical trial has been performed to determine the effect of temporary immobilization of the shoulder on wound drainage followitig radical mastectomy . In 64 patients admitted to the trial the mean volume of drainage was reduced by 40 per cent in those who had shoulder movement restricted for the first 7 days afer operation when compared with the group in whom early arm exercises were encouraged . The mean drainage time was reduced by 29 per cent . Shoulder immobilization did not result in increased shoulder stiffness , although there was an increased incidence of mild lymphoedema of the arm OBJECTIVE To determine if postoperative shoulder immobilization decreases the incidence of postmastectomy seromas . DESIGN AND SETTING A prospect i ve r and omized trial of three surgeons ' experiences at a community hospital . PATIENTS Thirty-eight patients who underwent modified radical mastectomy from March 1991 through February 1993 . MAIN OUTCOME MEASURES Incidence of postmastectomy seromas and time required for patients to gain 110 degrees of shoulder abduction after surgery . RESULTS Thirteen ( 72 % ) of 18 wounds in the maximum range of motion cohort developed seromas ( 72 % ) compared with one ( 6 % ) of 17 in the minimum range of motion cohort ( P = .0005 ) . The average time required for the patients with maximum range of motion to gain 110 degrees of shoulder abduction was 2.6 weeks , whereas the patients with minimum range of motion required an average of 5.0 weeks ( P = .0127 ) . CONCLUSION Postmastectomy shoulder immobilization significantly decreases the incidence of wound seromas . Although this protocol result ed in a delay in return to normal shoulder mobility , no patients sustained long-term musculoskeletal dysfunction After biopsy confirmation of breast carcinoma , women who were scheduled to undergo a modified radical mastectomy had demographic data collected , goniometric measurements of shoulder flexion and abduction , and functional evaluation of the ipsilateral shoulder performed , and upper extremity circumferential measurements at five levels determined . Patients were then r and omly assigned either to a group that received immediate postoperative physical therapy or to one that did not . Results represent the combination of data from a pilot study and this subsequent study following appropriate statistical analysis . Sixty-four women in the treatment group showed a statistically significant increase in shoulder range of motion in both abduction and flexion as compared to 51 women who received no physical therapy . The treated group also had fewer problems with five of the six upper extremity functional tasks that were assessed . There were no significant differences between the groups for length of hospital stay , postoperative complications , or upper extremity edema . The authors conclude that early physical therapy intervention makes a significant contribution to return to normal function without increasing the incidence of postoperative complications or prolonging hospital stay Background Wound seroma is one of the most frequent complications of mastectomy , but an effective strategy Tor its prevention has not yet been established . The purpose of this study was to determine the effectiveness of delayed shoulder exercise on the prevention of wound seroma after partial or total mastectomy with axillary dissection for the treatment of cancer . Methods This study prospect ively r and omized two exercise schemes after mastectomy with axillary lymph node dissection . The immediate exercise group ( n=58 ) started shoulder exercise on the first postoperative day . In the delayed exercise group ( n=58 ) the movement of the upper limb was limited to usual daily activities during the first postoperative week . Results Preoperative levels of shoulder function were regained within one month when shoulder exercise was delayed for one week after operation . Significant decrease of drainage volume and lower incidence of seroma formation were seen in the delayed exercise group . Conclusion These observations suggest that seven days of unrestricted movement and avoiding active exercise of the shoulder joint , is the optimal routine reduce seroma formation after mastectomy BACKGROUND There are several factors those contribute to the amount of axillary drainage after modified radical mastectomy . The drains should be removed as early as possible . Whether the active shoulder movement of the lesion side increases the amount of axillary drainage needs to be studied prospect ively . METHODS From 1994 through 1995 , 344 consecutive patients were r and omly divided into three groups . One hundred sixteen patients in the early group performed upper arm exercises including pendulum , wall climbing and pulley exercises beginning the third post-operative day . One hundred fifteen patients in the later group patients did the same exercises beginning the sixth post-operative day and 113 patients in the delayed group did the same exercises after all the drains were removed . RESULTS There were no significant differences in patient characteristics , including age , body weight , operation methods and the pathology in the three groups . The amount of axilla fossa drainage was significantly less in the patients in the delayed group than in the early and later group ( 485 ml , 568 ml , 559 ml , respectively , p = 0.032 ) . However , there were no differences in the amount of chest wall site drainage or the number of aspiration of seroma among the three groups . The drains were removed on the average of seventh and ninth post-operative day in the delayed and early group patients , respectively ( p = 0.124 ) . Although the range of motion ( ROM ) of the shoulders in the delayed group patients was slightly limited during the first month after operation , ROM returned at 3 months and no difference was found 6 months after operation . CONCLUSION Upper arm exercise can start after the drains in the axilla are removed . The delay does not limit the shoulder function at 6 months after modified radical mastectomy A prospect i ve r and omized study was carried out to discover the influence of the timing of shoulder physiotherapy after-axillary dissection for breast cancer upon the incidence and duration of lymphatic fluid production and seroma after these operations . Sixty-eight patients underwent a modified radical mastectomy , 31 were su bmi tted to early physiotherapy and 37 to delayed physiotherapy after removal of the suction drainage . In 32 patients this surgery was conservative of the breast ; in 16 the physiotherapy was early and in 16 delayed . The shoulder was left free when the physiotherapy was delayed . The mean volume of lymphatic fluid produced after these 100 axillary dissections was 437 cc ( range : 50 to 800 cc ) with a mean duration of 6.3 days ( range : 2 to 11 days ) . There was a linear relation between the volume and the duration of the lymphatic fluid production . This volume was significantly higher in radical mastectomy than in conservative procedures ( 486 cc vs 333 cc - p less than 0.02 ) . There was no significant difference in the production of lymphatic fluid with early or delayed physiotherapy , whatever the group of patients : radical or conservative surgery - age - number of excised lymph nodes - lymph node involvement . Five seromas occurred in patients with delayed physiotherapy . Delaying physiotherapy after axillary dissection for breast cancer does not seem to reduce the incidence of lymphatic complication , but the use of a conservative procedure rather than a modified radical mastectomy seems to be able to do so Greater amount and duration of postoperative wound drainage after lymphadenectomy impede healing . We evaluated the influence of early vs delayed initiation of shoulder mobilization on postoperative drainage . Fifty-seven women with clinical stage I or II breast cancer were r and omized to either early ( postoperative day 2 ) or delayed ( postoperative day 5 ) shoulder motion . Early vs delayed time of exercise initiation had no effect on total amount or duration of drainage , either as an inpatient or outpatient . The two groups were determined to be homogeneous as to age , breast size , weight , height , obesity , previous biopsy , excision of pectoralis minor , excision of thoracodorsal complex , level of axillary dissection , total number of lymph nodes , number of positive lymph nodes , lymphatic vessel invasion ( with negative lymph nodes ) , and whether the dominant h and was on the side operated on . The two factors predicting greater drainage were large numbers of positive lymph nodes and no previous surgical biopsy ( as in one-step procedure ) A total of 144 evaluable patients with breast cancer were enrolled in a multicenter , r and omized , prospect i ve study to establish the role of delayed shoulder exercises on wound drainage and shoulder function after axillary lymph node dissection . Patients in group 1 ( n = 78 ) started active shoulder exercises 1 day postoperatively . Patients in group 2 ( n = 66 ) started on the eight postoperative day , following 1 week of immobilization of the arm . Patients in group 2 had 14 % less wound drainage volume than those in group 1 ( 600 + /- 436 mL versus 701 + /- 398 mL ) ; this difference , however , was not significant . Also , no differences could be established between the two groups when duration and volume of wound drainage , number and volume of seroma aspirations , wound complication rates , and shoulder function were compared 6 months after surgery |
577 | 21,912,769 | The present meta- analysis did not find a significant effect of steroid over st and ard therapy , either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP . | BACKGROUND The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia ( BA ) is unclear .
OBJECTIVE To systematic ally review the literature and perform a meta- analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy ( KP ) on BA outcome . | Although the Kasai operation is still the treatment of choice for infants with biliary atresia , the long-term success rate , as defined by survival without transplantation , is only about 25–40 % . It has been proposed that post-operative inflammatory changes affect the bile flow and eventually lead to cholangitis and liver failure . Recent case reports have suggested that the administration of steroids post-operatively can improve outcomes . Since 2004 , our unit has adopted a strict protocol for the use of post-operative steroids for patients who undergo Kasai operation . The aim of this study is to access the early outcomes of these patients . A retrospective analysis was carried out for all patients who received Kasai operation between 1996 and 2006 . For the treatment group , patients all received prednisolone at 4 mg/kg 1 week after operation as guided by protocol . The demographics and outcomes , including post operative bilirubin level , episodes of cholangitic attack , the need for early liver transplantation ( transplant within 1 year of Kasai ) , and transplantation-free survival , were noted . Statistical analysis was done using Fisher ’s exact test and unpaired t-test when appropriate . A value of P < 0.05 was considered to be statistically significant . Kasai operation was performed in 30 patients ( 11 boys and 19 girls ) during the study period . Thirteen patients received post-operative prednisolone according to protocol . The average age at operation and the mean preoperative bilirubin levels for the steroid and non-steroid group were not significantly different . A normal post-operative bilirubin ( defined as bilirubin level less than 20 μmol/L ) was achieved at 6 months in 7 ( 53.9 % ) patients who received steroid and 8 ( 47.0 % ) patients who did not ( P = 0.71 ) . A statistically significant reduction in the post-operative bilirubin level was also seen at 3 and 6 months in the steroid group . Early liver transplantation was required in 5 ( 38.5 % ) patients with steroid and 5 ( 29.4 % ) patients without it ( P = 0.60 ) . No significant difference in terms of cholangitic attack was observed . There was also no steroid-associated complication reported . We conclude that lower post-operative bilirubin level can be achieved with the routine use of prednisolone . However , there is no statistical improvement in terms of early liver transplantation and cholangitis . This may be attributed to the small sample size of our study population . Based on this pilot study , a multi-centre r and omized trial is needed OBJECTIVE : Postoperative adjuvant steroid treatment is reported to improve jaundice-free survival in biliary atresia ( BA ) patients and to reduce the need for early liver transplantation . However , evidence of all retrospective studies is very limited , although high-dose corticosteroids were favored . The aim of this dosage finding study was to test the most promising corticosteroid protocol in a smaller but representative series , in order to optimize the setting s of upcoming prospect i ve and long-term multicenter studies . METHODS : Our prospect i ve single-center and open-labeled pilot study on high-dose steroids included 49 consecutive BA patients . Basic data of the study group were not different from 29 controls . In the study group , 20 consecutive patients were treated after the Kasai with methylprednisolone ( 10 mg/kg day 1 to 5 and 1 mg/kg day 6 to 28 ) . RESULTS : Overall survival with native liver was 63 % after 6 months and 31 % after 2 yr , with no statistical difference between the study and control groups . After 2 yr , 27 % of all patients were still jaundice-free . With regard to predictive parameters , we found , 6 months after the Kasai , bilirubin < 20 μmol/L as highly sensitive ( 97 % ) and specific ( 93 % ) for jaundice-free survival with native liver . CONCLUSIONS : In contrast to previous reports , this pilot study shows that high-dose steroid pulses after Kasai procedure are not effective in postoperative adjuvant therapy protocol s and should be avoided in upcoming multicenter steroid studies . Therefore , we recommend extended and r and omized multicenter studies to pre-evaluate the supposed effectiveness of alternative steroid protocol s , by comparing , 6 months after the Kasai procedure , the number of patients with normal bilirubin BACKGROUND / PURPOSE Despite improvements in the surgical management of biliary atresia , the long-term incidence of progressive liver failure remains high . Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology , the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy . The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia . METHODS A retrospective analysis of all patients with biliary atresia treated with an hepatoportoenterostomy and postoperative steroid therapy at our 3 institutions was undertaken . Patients were treated uniformly with immunosuppressive doses of oral steroids for a minimum of 6 weeks after surgery . RESULTS Twenty-five infants with biliary atresia were treated with steroid therapy . Overall survival rate was 22 patients ( 88 % ) with a mean follow-up period of 50 months . Nineteen patients ( 76 % ) became jaundice free with native liver function . Four patients ( 16 % ) did not respond to treatment and required transplantation . Age less than 12 weeks was a crucial predictor of success of adjuvant steroid therapy . Cholangitis developed in 8 patients ( 32 % ) . There were no complications caused by steroid therapy . CONCLUSIONS Steroid administration at immunosuppressive doses markedly improves the clinical outcome within the first 5 years after surgery as measured by jaundice-free status and survival without liver transplantation when compared with concurrent reports . These results suggest that immunosuppressive therapy is safe and has a positive impact on the clinical course of this disease . However , a r and omized study is needed to ultimately prove such an hypothesis Controversy exists regarding the efficacy of corticosteroids on bile flow after Kasai portoenterostomy in biliary atresia ( BA ) . Fourteen patients who had BA and underwent Kasai portojejunostomy between November 1990 and March 1996 were subject of this study . Corticosteroid therapy ( " blast " type ) was used for inadequate bile drainage . Corticosteroid support was unnecessary in one patient with good bile drainage , and corticosteroids were aggressively used in the remaining 13 patients . Two patients who had no response to an initial blast subsequently responded and now are doing well . The remaining 11 patients responded to corticosteroids with varying degrees . Three had a limited response , and two ultimately underwent liver transplantation . There was one death caused by subdural hematoma . Three had an excellent initial response . However , one subsequently deteriorated because of intractable cholangitis , requiring liver transplantation . Ten survivors with native liver are anicteric with satisfactory growth and quality of life . Aggressive corticosteroid therapy is an important part of the management after Kasai portoenterostomy . The initial response to steroids does not necessarily reflect the final outcome PURPOSE This study tests the hypothesis that steroid administration improves the outcome of biliary atresia ( BA ) by evaluating the efficacy of postoperative steroid use on surgical outcomes in infants with BA . METHODS Steroid use and outcomes in patients with BA were retrospectively analyzed at a tertiary pediatric hospital . Institutional review board approval was obtained . RESULTS Kasai portoenterostomy ( PE ) was performed in 43 patients with BA treated from 1992 to 2004 ( 16 boys and 27 girls ) . Twenty-one PE patients received steroids and 22 did not . Portoenterostomy was successful in 24 patients ( 55.8 % ) with consistent serum bilirubin less than 2 mg/dL. Sixteen ( 66 % ) received postoperative steroids . A normal postoperative bilirubin was achieved at 6 months in 16 ( 76 % ) of 21 patients with steroids compared with 8 ( 37 % ) of 22 in untreated controls ( Fisher 's Exact test , P = .01 ) . Of the 43 patients , 19 ( 44 % ) required liver transplantation , including 7 ( 37 % ) of 19 with steroids vs 12 ( 63 % ) of 19 without ( P = .2 ) . Twenty-eight infants developed cholangitis ( fever with and without changes in hepatic function ) : 25 after PE and 3 after transplant . Of the 25 , 12 ( 48 % ) received steroids . Seven died ( 16 % ) ( range , 7 months to 4 years ) : 2 while awaiting transplantation ( received steroids ) and 5 after transplantation ( 1 received steroids and 4 were untreated ) . Survival was 86 % ( 18/21 ) in patients with steroids and 82 % ( 18/22 ) in those without . Transplant survival ( 74 % ) was comparable to previously reported historical controls ( 82 % ) . CONCLUSIONS The Kasai PE continues to be the procedure of choice in infants with BA younger than 3 months . A significantly improved clearance of postoperative jaundice and lower serum bilirubin levels were observed in patients receiving steroids . However , steroids had no effect on the incidence of cholangitis , need for liver transplantation , and overall survival . A prospect i ve study with st and ardized dose and length of steroid administration and longer period of follow-up is necessary to more accurately assess the effectiveness of steroids after PE The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia . The study consisted of a prospect i ve , 2‐center , double‐blind , r and omized , placebo‐controlled trial of post – Kasai portoenterostomy corticosteroids ( oral prednisolone : 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28 ) . The data were compared with χ 2 or Mann‐Whitney tests , as appropriate . Seventy‐one postoperative infants with type 3 biliary atresia were r and omized to receive either oral prednisolone ( n = 36 ) or a placebo ( n = 37 ) . At 1 month , the median bilirubin level was lower in the steroid group ( 66 versus 92 μmol/L , P = 0.06 ) , but no difference was evident at 6 ( P = 0.56 ) or 12 ( P = 0.3 ) months . The proportion of infants with a normal bilirubin level ( < 20 μmol/L ) at 6 ( 47 % versus 49 % , P = 0.89 ) and 12 months ( 50 % versus 40 % , P = 0.35 ) was not significantly different . The need for transplantation by 6 ( 12 % versus 13 % , P = 0.99 ) and 12 months ( 26 % versus 35 % , P = 0.47 ) was not significantly different . The steroid effect was more pronounced in younger infants ( less than 70 days at Kasai portoenterostomy , n = 51 ) , with a reduced bilirubin level at 1 month ( 64 versus 117 μmol/L , P = 0.01 ) and with a greater proportion with a normal bilirubin level at 12 months ( 54 % versus 37 % , P = 0.22 ) . Conclusion : There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period ( specifically in infants less than 70 days old at surgery ) , but this steroid regimen did not reduce the need for liver transplantation . ( HEPATOLOGY 2007;46:1821–1827 . |
578 | 17,943,740 | AUTHORS ' CONCLUSIONS Deworming drugs used in targeted community programmes may be effective in relation to weight gain in some circumstances but not in others .
No effect on cognition or school performance has been demonstrated | BACKGROUND In areas where intestinal worm infections occur , the World Health Organization recommends treating all school children at regular intervals with deworming drugs to improve growth and school performance .
The evidence base for this policy needs to be established for countries to commit re sources to implement these programmes .
OBJECTIVES To summarize the effects of deworming drugs used to treat soil-transmitted intestinal worms ( nematode geohelminths ) on growth and school performance in children . | 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 The prevalence rate of ascariasis in primary school children in northern Jakarta , Indonesia varies from 60 % to 90 % . An association between helminthic infection and educational achievement has long been recognized . This study was carried out in the northern part of Jakarta among primary school children 6 - 8 years of age . Treatment of ascariasis and health education were used as the interventions . Before the interventions , basic data on socioeconomic status , epidemiology , infection with Ascaris lumbricoides , nutritional status , and cognitive function were collected . After the interventions , only data on infection with A. lumbricoides , nutritional status , and cognitive function were collected . The children were divided into five groups . Group I was given an anthelminthic ( mebendazole ) , group II was provided with health education , group III was given an antihelminthic and provided with health education , group IV was given a placebo ( controls ) , and group V consisted of egg-negative children , who also served as controls . Data from 336 students were analyzed by analysis of covariance . Parasitologic examinations showed a mean prevalence rate of 58.4 % for A. lumbricoides infection in the pre-intervention children and a mean prevalence rate of 40.6 % in the post-intervention children . Concerning nutritional status , approximately 80 % of the children showed good scores in the pre- and post-treatment data , and only a small percentage ( 0.9 - 16.2 % ) showed mild or moderate malnutrition . No significant difference was found between the pre- and post-treatment nutritional status . The results of the cognitive test showed that the group treated with mebendazole showed significant improvement in the Colored Progressive Matrices and Coding test . Children also showed an improvement in their learning ability , concentration , and eye-h and coordination after five months of receiving this intervention BACKGROUND The effect of helminth infestation on the nutrition , growth , and physiology of the host is still poorly understood . Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements . OBJECTIVE The objective of this study was to assess the effect of regular deworming on child growth , physiology , and biochemical status . DESIGN The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2 - 5 y. Treatment ( mebendazole ) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo . Weight , height , midupper arm circumference , intestinal permeability , plasma albumin , alpha(1)-antichymotrypsin , and total protein concentration were assessed every 2 mo . RESULTS Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78 % to 8 % , of Trichuris trichiura from 65 % to 9 % , and of hookworm from 4 % to 0 % . There was no significant difference in the growth of treated children compared with those given placebo tablets . No changes in intestinal permeability or plasma albumin were observed after deworming . Significant decreases in total protein ( P<0.001 ) and alpha(1)-antichymotrypsin ( P<0.001 ) were observed in the treatment group , indicating possible reductions in inflammation and immunoglobulin concentration after deworming . A significant increase in the prevalence of Giardia intestinalis ( from 4 % to 49 % ) in the treatment group was associated with a short-term reduction in weight ( P = 0.02 ) and higher intestinal permeability ( P < 0.001 ) in infected subjects . No long-term effects of G. intestinalis on growth were observed . CONCLUSION Low-intensity helminth infections , predominantly of A. lumbricoides and T. trichiura , do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children We studied growth in infected children given one dose ( 600 mg ) or two doses of albendazole per school year . Children were examined and allocated at r and om within sex by descending hookworm egg count to one of three groups : placebo ( n = 93 ) , one dose ( 1x , n = 96 ) or two doses ( 2x , n = 95 ) . Each child was treated and then re-examined and treated 3.6 and 8.2 mo later ( Exams 2 and 3 ) . The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight ( 1.1 and 0.9 kg more , respectively ) , percent weight-for-age ( 3.3 and 2.7 percentage points more ) , percent weight-for-height ( 3.1 and 2.9 percentage points more ) , percent arm circumference-for-age ( 2.3 and 2.0 percentage points more ) and triceps and subscapular skinfolds but did not differ significantly from each other . The placebo group showed significant decreases between exams ( P < 0.0002 ) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height , whereas the 1x and 2x groups exhibited significant increases ( P < 0.005 ) . At Exam 3 , arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95 % for hookworm , 42 and 32 % for Trichuris and 55 and 87 % for Ascaris , respectively . We conclude that one or two doses of albendazole per year result ed in similar growth improvements , despite reinfection , in school-age children in an area where these helminths and poor growth are prevalent We studied physical fitness with the Harvard Step Test , growth , and appetite in primary school boys infected with hookworm ( 96 % baseline prevalence ) , Trichuris trichiura ( 98 % prevalence ) and Ascaris lumbricoides ( 41 % prevalence ) who received a single 600-mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om within pairs by descending hookworm egg count to placebo ( n = 26 ) or albendazole ( n = 27 ) groups , treated , and re-examined 4 mo later . Four months after treatment , the albendazole group showed highly significant improvements in fitness score , resting heart rate , and heart rates at 1 , 2 , 3 and 4 min after the Harvard Step Test , whereas the placebo group had not changed significantly . The albendazole group also exhibited significantly more rapid growth judged by weight gain ( 1.0 kg greater than the placebo group , P < 0.0002 ) , height increment ( 0.6 cm more , P < 0.003 ) , arm circumference ( 0.3 cm more , P < 0.0002 ) , and triceps and subscapular skinfolds ( 1.0 mm more , P < 0.0002 ) , and showed improved appetite with objective and subjective measures . We conclude that single-dose treatment with albendazole can allow improved physical fitness , growth , and appetite in school-age children in areas where these helminths and poor growth are highly prevalent A r and omized controlled trial was conducted in eastern Zaire to assess the effects of high dose vitamin A supplementation and regular deparasitation on the growth of 358 moderately malnourished preschool children , discharged from the hospital . The treatment groups received either vitamin A ( 60 mg of oily solution of retinyl palmitate , 30 mg if aged < 12 mo ) every 6 mo or mebendazole ( 500 mg ) every 3 mo ; the control group received no supplementation . Anthropometric data were gathered at baseline and after 6 and 12 mo of follow-up . Serum retinol concentrations were measured at baseline and after 3 mo . The three groups did not differ in sociodemographic indicators , age and sex composition , nutritional status and serum retinol concentrations at baseline . In children who were vitamin A deficient at baseline , adjusted mean weight and mid-upper arm circumference ( MUAC ) increments were higher in the vitamin A-supplemented group than in the control group [ annual increment in weight and MUAC in vitamin A vs. control group : 2.088 vs. 1.179 kg ( P = 0.029 ) and 2.24 vs. 0.95 cm ( P = 0.012 ) , respectively ] , whereas growth increment did not differ between the dewormed group and the control group . In children who were not vitamin A deficient at baseline , growth increment did not differ between the vitamin A-supplemented and control groups , whereas weight gain was lower in the dewormed group than in the control group . Vitamin A-supplemented boys gained more weight and height than control boys , whereas vitamin A-supplemented girls gained less height than control girls . Dewormed boys and girls gained less weight than control boys and girls . Programs to improve vitamin A status by high dose vitamin A supplementation may improve growth of preschool children who are vitamin A deficient , whereas deworming does not Efficacy trials of antihelminthic therapies conducted in Africa have reported improvements in children 's growth , but nutritional evaluations of large-scale deworming programs are lacking . We evaluated the first-year effect on growth of a school-based deworming program in Zanzibar , where growth retardation occurs in school children . Children in four primary schools were given thrice-yearly mebendazole ( 500 mg ) and compared with children in four schools that received twice-yearly mebendazole and children in four non-program schools . Evaluation schools were r and omly selected and allocated to control , twice-yearly or thrice-yearly deworming . Approximately 1000 children in each program group completed the 1-y follow-up . Children < 10 y old gained 0.27 kg more weight ( P < 0.05 ) and 0.13 cm more height ( P = 0.20 ) in the twice-yearly group , and 0 . 20 kg more weight ( P = 0.07 ) and 0.30 cm more height ( P < 0.01 ) in the thrice-yearly group , compared with the control group . Children < 10 y old with higher heights-for-age at baseline had higher weight and height gains in response to deworming . In children > /=10 y old , overall program effects on height or weight gains were not significant . But in this age range , younger boys had significant improvements in height gain with thrice-yearly deworming , and children with higher heights-for-age had greater improvements in weight gain with deworming . We conclude that the deworming program improved the growth of school children , especially children who were younger and less stunted , but the improvements were small . More effective antihelminthic regimens or additional dietary or disease control interventions may be needed to substantially improve the growth of school children in areas such as Zanzibar We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children . Parasitologic and nutritional assessment s were carried out at baseline , 6 mo , and 12 mo in 4 nonprogram schools ( n = 1002 ) , 4 schools in which students received twice-yearly deworming ( n = 952 ) , and 4 schools in which students received thrice-yearly deworming ( n = 970 ) with 500 mg generic mebendazole . Schools were r and omly selected for evaluation and allocated to program groups . Relative to no treatment , thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations . The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups , respectively ( P < 0.001 ) . The average changes in ferritin concentration were 2.8 and 4.5 microg/L , respectively ( P = 0.07 ) . Deworming had no effect on annual hemoglobin change or prevalence of anemia . However , the relative risk of severe anemia ( hemoglobin < 70 g/L ) was 0.77 ( 95 % confidence limits : 0.39 , 1.51 ) in the twice-yearly deworming group and 0.45 ( 0.19 , 1.08 ) in the thrice-yearly deworming group . The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia ( hemoglobin < 90 g/L ) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline . We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic , deworming programs can improve iron status and prevent moderate and severe anemia , but deworming may be needed at least twice yearly Iron deficiency and helminth infections are two common conditions of children in developing countries . The consequences of helminth infection in young children are not well described , and the efficacy of low dose iron supplementation is not well documented in malaria-endemic setting s. A 12-mo r and omized , placebo controlled , double-blind trial of 10 mg daily iron and /or mebendazole ( 500 mg ) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6 - 71 mo with hemoglobin > 70 g/L at baseline . The trial was design ed to examine treatment effects on growth , anemia and appetite in two age subgroups . Iron did not affect growth retardation , hemoglobin concentration or mild or moderate anemia ( hemoglobin < 110 g/L or < 90 g/L , respectively ) , but iron significantly improved serum ferritin and erythrocyte protoporphyrin . Mebendazole significantly reduced wasting malnutrition . but only in children < 30 mo old . The adjusted odds ratios ( AORs ) for mebendazole in this age group were 0.38 ( 95 % CI : 0.16 , 0.90 ) for weight-for-height less than -1 Z-score and 0.29 ( 0.09 , 0.91 ) for small arm circumference . In children < 24 mo old , mebendazole also reduced moderate anemia ( AOR : 0.41 , 0.18 , 0.94 ) . Both iron and mebendazole improved children 's appetite , according to mothers ' report . In this study , iron 's effect on anemia was limited , likely constrained by infection , inflammation and perhaps other nutrient deficiencies . Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections . We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children , with deleterious effects on protein metabolism and erythropoiesis One-hundred eighty-five Bangladeshi children age 1 1/2 to 8 yr with no Ascaris lumbricoides infection or with light , moderate , or heavy infection were r and omly assigned to treatment of placebo groups , with treatment given in a double-blind fashion . The groups were comparable for nutritional and socioeconomic parameters . Treatment consisted of a single dose of piperazine citrate administered twice within a 2-wk period . The cure rates for the low , moderate , and heavy A. lumbricoides infected subgroups were 53 , 31 , and 36 % , respectively . With more severe infections , worm eradication was more difficult and the rate of reinfection after treatment was more rapid . The rate of reinfection was significantly different for the low A. lumbricoides infected treatment and placebo subgroups for 5 months after treatment , for the moderate treatment and placebo subgroups for 3 months after treatment , and for the heavy A. lumbricoides infected treatment and placebo subgroups there was a difference , although not significant , for 1 month after treatment . Anthropometric measurements were obtained for a period of 11 months . Analysis of covariance revealed no significant difference for change of weight , change of height , weight-for age , weight-for-height , height-for-age , triceps skinfold , midarm circumference , and the abdominal girth to chest circumference ratio between the treatment and placebo groups after drug administration . The results of this study do not support single dose worm therapy as a means to enhance growth The effect of weekly iron supplementation with and without deworming on hemoglobin was investigated in a double-masked , placebo-controlled field trial . Subjects were 289 preschoolers who were r and omly divided into three groups . Groups 1 and 2 received 30 mg Fe once weekly and group 3 received a placebo . Group 1 additionally received anthelminthic treatment . Supplements were administered by the mothers , who were educated about iron deficiency beforeh and . In the iron-supplemented groups prevalence of anemia decreased from 37.2 % to 16.2 % ( P < 0.001 ) . Hemoglobin increased by an average of 6.9 + /- 9.8 g/L in the two iron-supplemented groups ( n = 191 ) , which was greater ( P < 0.001 ) than the increase of 1.9 + /- 8.0 g/L in the placebo group . None of the subjects had hookworm , and anthelminthic treatment did not have an additional effect . Iron supplements administered once weekly by mothers reduced anemia without major involvement of health staff Growth , activity , appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm ( 93 % prevalence ) , T. trichiura ( 84 % prevalence ) and A. lumbricoides ( 29 % prevalence ) before and 9 wk after treatment with three 400-mg doses of albendazole ( Zentel ) or placebo . Fecal sample s were examined for helminth eggs using a modified Kato technique . Activity was measured during free-play with motion recorders on the dominant thigh . Children rated their appetites on a 5-point scale . After baseline measurements , children were r and omly allocated to the albendazole-treated ( n = 28 ) and placebo ( n = 27 ) groups , treated , and re-examined 9 wk later . At follow-up , egg counts were significantly lower than at baseline in the albendazole-treated group ( P < or = 0.002 ) , and gains in activity , reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group . We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity One hundred fifty-nine children aged 24 to 61 months with 60 % ascariasis prevalence and 21.5 % giardiasis prevalence in rural Guatemala were studied prospect ively for 1 yr . They were divided into four groups comparable for age , sex , socioeconomic status , and past growth experience as judged by slopes of height and weight on age . Each group was r and omly assigned to the following 2-monthly treatment regimens : group I , placebo , group II , piperazine , group III , metronidazole ; group IV , piperazine and metronidazole . Height and weight were measured every 3 months and stools were examined for parasites every 4 months . Piperazine administration decreased the prevalence of ascariasis to 33.8 % at the end of the study but growth remained unaltered . Metronidazole administration decreased the prevalence of giardiasis to 2.5 % at the end of the study and was accompanied by increased growth as judged by delta weight , delta % weight for age , slope of weight on age , delta height , delta % height for age and slope of height on age . It is suggested that failure of antiascaris treatment to enhance growth in this study may be because of 1 ) absence of severe malnutrition in the subjects , 2 ) adequacy of dietary protein , 3 ) possible low worm load , and 4 ) failure to eradicate ascariasis . The findings suggest that giardiasis is associated with reduced growth in preschool children The effects of treating Trichuris trichiura infections were investigated in 407 Jamaican children age 6 to 12 y. The children were r and omly assigned to receive treatment ( albendazole ) or a placebo . The outcome variables included growth , tests of reading , spelling and arithmetic , and school attendance . After 6 mo of treatment , there was no significant main effect on any of the outcomes . However , there were significant treatment-by-infection intensity interactions with spelling ( P < 0.05 ) and body mass index ( P < 0.01 ) , and a significant treatment-by-stunting interaction with school attendance ( P < 0.01 ) . In spelling , the children with heavy infections showed improvements with treatment that approached significance ( P = 0.06 ) , whereas those with lower intensities did not . However , the children with lower infection intensities had increased body mass index with treatment ( P = 0.02 ) , although there was no difference in children with heavy infections . In school attendance , the stunted children improved with treatment ( P < 0.04 ) , whereas there was no difference in the nonstunted children . These findings suggest that in the sample of Jamaican children examined , the treatment of T. trichiura was more likely to benefit school performance in children of poor nutritional status and those with heavy infections , and to improve weight gain in children with lighter infection intensities A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura ( whipworm ) infection on the cognitive functions of 159 school children ( age 9 - 12 years ) in Jamaica . Infected children were r and omly assigned to Treatment or Placebo groups . A third group of r and omly selected uninfected children were assigned to a Control for comparative purpose s. The improvement in cognitive function was evaluated using a stepwise multiple linear regression , design ed to control for any confounding variables . The expulsion of worms led to a significant improvement in tests of auditory short-term memory ( P less than 0.02 ; P less than 0.01 ) , and a highly significant improvement in the scanning and retrieval of long-term memory ( P less than 0.001 ) . After 9 weeks , treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function . The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement . The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy Objective : To assess the effects of iron and deworming on linear growth performance of preschoolers . Design : Three-month r and omized , double-blind and placebo-controlled trial . The children were allocated to four treatments : iron ( 60 mg elemental iron/day)+albendazole ( 200 mg/day for 3 consecutive days , repeated 1 month later ) , iron+albendazole-placebo , albendazole+iron-placebo or placebos . The supplementation was supervised . Subjects : A group of 177 children aged 3–5 y was selected from low-income households in a rural area in southern Bénin . A complete data set was analysed for 140 subjects . Many children were stunted ( 58 % had height-for-age Z-score < −2 ) , none were wasted ( 2 % had weight-for-height Z-score < −2 ) and 76 % were anemic ( Hb<110 g/l).Main outcome measures : Anthropometric parameters , hemoglobin and eggs per gram feces . Results : No significant difference in changes in anthropometric parameters was observed between study groups , and also not in a sub- sample of stunted and anemic subjects . Changes in hemoglobin were highest in the iron-treated subjects at the end of the 3-month intervention period ( P=0.032 ) . The difference between the iron and the placebo groups remained significant even 7 months later ( P=0.022 ) . The difference was 5 g/l in both periods . Ascaris lumbricoides and hookworm infections decreased significantly in albendazole-treated subjects ( P<0.05 ) . Conclusions : In addition to recurrent parasitic infection burden , the children may have multiple micronutrient deficiencies . Therefore , it may be interesting to study appetite and food intake of young toddlers in relation to health and linear growth performance in poor environments . Sponsorship : The Nestlé Foundation ( Lausanne , Switzerl and ) .European Journal of Clinical Nutrition ( 2001 ) 55 , Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children ( K-ABC ) adopted to the language of Kituba . Within a day of this test , each child was evaluated for blood hemoglobin ( Hgb ) level and the presence of intestinal parasites . Half of the children received an iron supplement ( 20 mg Fe ) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were r and omly selected to receive either a vermifuge treatment or placebo . All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment . Using discriminant analysis , performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb result ed in the successful classification of 74 % in terms whether a child had received both iron supplement and vermifuge treatment ( p = .007 ) . With respect to our home evaluation for each child , factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability . However , the present findings also suggest that over the short-term , changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability , perhaps by means of heightened attentional capacity This r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample The association between helminth infection and cognitive and motor function was investigated in school-age children in Java , Indonesia . 432 children from 42 primary schools participated in the study . Children were stratified by age and sex into two age groups , 8 - 9 years and 11 - 13 years . Children infected with hookworm performed significantly worse than children without hookworm infection in 6 of the 14 cognitive or motor tests . After controlling for school ( as a r and om effect ) plus age , socio-economic status and parental education , sex , stunting ( height-for-age < - 2sd ) , body mass index , haemoglobin concentration and the presence of A. lumbricoides and T. trichiura infections , infection with hookworm explained significantly lower scores on tests of Fluency ( P < 0.01 ) , Digit-Span Forwards ( P < 0.01 ) , Number Choice ( P < 0.01 ) , Picture Search ( P < 0.03 ) , Stroop Colour Word ( P < 0.02 ) and Mazes ( P < 0.001 ) . In 4 of the 6-tests ( Fluency , Number Choice , Picture Search and Mazes ) , there was a significant interaction between hookworm infection and age ( P < 0.03 ) , indicating that the association between hookworm and lower test scores increased with age . No associations were observed between hookworm infection and scores in tests of Digit-Span Backwards , Corsi-Block , Stroop Colour , Stroop Interference , Free Recall , Verbal Analogies , Bead Threading or the Pegboard ( P > 0.05 ) . Tests associated with helminths represented various functions of working memory . No significant associations between helminth infection and motor function were observed that could not be explained by chance . The results suggest that hookworm infection can have a significant adverse effect on children 's working memory which may have consequences for a child 's reasoning ability and reading comprehension . Although the results are only associational , the fact that differences in cognition were observed at baseline imply that preventing infection with helminths in school-age children could be of benefit Objective : The study was conducted to assess the effectiveness of six monthly albendazole ( ABZ ) for improving the weight and height of preschool children when initia ted at 0.5–1 year of age in population s with a high transmission rate of intestinal roundworm , Ascaris lumbricoides . It was a cluster r and omized trial in the urban slums of Lucknow , North India . Methods : Control children received 2 ml ( 1 ml to infants ) of Vitamin A every six month whereas those in the ABZ areas received , in addition , 400 mg of ABZ suspension ( Zentel , SKB ) every six month . Sixty-three and sixty-one slum areas were r and omized to albendazole ( ABZ ) or to control groups , respectively . Children aged 0.5–1 year were recruited in April 1996 and followed up for 1.5 years . Of 1022 children recruited from control and 988 from ABZ areas , the loss to follow-up at 1.5 year was 15.6 % and 14.6 % respectively . Mean ( ±SE ) weight gain in Kg in control versus ABZ areas was 3.04 ( 0.03 ) versus 3.22 ( 0.03 ) , ( p=0.01 ) . Results : After controlling for the presence of weight-for age z-score < -2.00 at enrollment in the ordinary least square ’s regression model , the extra weight gain in 1.5 years in those who received ABZ plus vitamin A was 0.13 Kg ( 95 % Cl:0.004 to 0.26 Kg . , p value=0.043 ) when compared to those who received only vitamin A ; underweight children at enrollment benefiting more than the normal ones . Conclusion : It was concluded that there was an improvement in weight with six monthly ABZ over 1.5 years . However , a much larger trial would be needed to determine whether there is any net effect of improvement in weight on under five mortality rate Anthelmintic treatment of sick preschool-age children at health facilities is a potentially effective strategy for intestinal helminth control in this age-group . We conducted a study from July 1998 to February 1999 in western Kenya to determine whether the Integrated Management of Childhood Illness ( IMCI ) guidelines ' clinical assessment can be used to identify helminth-infected children , and to evaluate the nutritional benefit of treating sick children without pallor with an anthelmintic ( mebendazole is already part of IMCI treatment for sick children aged 2 - 4 years with palmar pallor in areas where hookworm and Trichuris trichiura infections are endemic ) . Sick children aged 2 - 4 years seen at 3 rural health facilities were clinical ly evaluated and tested for haemoglobin concentration , malaria parasites , and intestinal helminths . Children without pallor were r and omly assigned to receive a single dose of 500 mg of mebendazole or a placebo and re-examined 6 months later . Among the 574 children enrolled , 11 % had one or more intestinal helminths . Most infections were of light intensity . Selected clinical signs and symptoms available from the IMCI assessment , including palmar pallor and low weight-for-age , were not associated with helminth infection . Six months after enrollment , no differences in growth of children without pallor were observed between the mebendazole ( n = 166 ) and placebo ( n = 181 ) groups . However , there was a significantly greater mean increase in weight , height , and weight-for-age Z score among the helminth-infected children in the mebendazole group ( n = 22 ) as compared with helminth-infected children in the placebo group ( n = 20 ) . We conclude that even lightly infected preschool-age children without palmar pallor benefit from anthelmintic treatment ; however , in this study setting of low helminth prevalence and intensity , helminth-infected children could not be identified using the IMCI guidelines . Cost-effectiveness studies are needed to help define helminth prevalence thresholds for routine anthelmintic treatment of sick preschool-age children seen at first-level health facilities This study examined the relationship between intestinal helminthiases and growth in urban slum schoolchildren . Children ( n = 330 ) who received single doses of either pyrantel , albendazole , or placebo at baseline and again at 6 months were followed and examined fully at 0 , 3 , 6 , and 12 months for helminth infections and anthropometry . Results of treatments indicated that all groups reduced their prevalence and intensity toward the period of the study . Reductions in intensity of both infections in the treatment groups were observed large in 3 and 12 months , whereas at 6 months reached mostly the initial level of infection . There was no significant difference in growth changes between the dewormed ( once and twice ) and the placebo groups . However , after controlling for some potential confounding factors , there was a significant relationship between reduction of A. lumbricoides infection and height gain at 3 and 12 months ( both P < 0.05 ) . In addition , there was a significant association between reduction in T. trichiura infection and increased midarm circumference at 3 and 12 months ( P < 0.002 and P < 0.08 , respectively ) . We conclude that treatment of helminth infections in school-age children may improve growth in areas where malnutrition and helminth infections are prevalent This r and omized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were r and omly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions Summary Single interventions for helminthic infections and micronutrient deficiencies are effective , but it is not clear whether combined interventions will provide equal , additive or synergistic effects to improve children 's health . The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children . A double-blind , r and omized , placebo-controlled trial in 11 rural South African primary schools r and omly allocated 579 children aged between 8 and 10 years into six study groups , half of whom received antihelminthic treatment at baseline . The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits , either unfortified or fortified with vitamin A and iron or with vitamin A only , given daily for 16 weeks . The outcome measures were anthropometric , micronutrient and parasite status , and scholastic and cognitive test scores . There was a significant treatment effect of vitamin A on serum retinol ( p < 0.01 ) , and the suggestion of an additive effect between vitamin A fortification and de-worming . Fortified biscuits improved micronutrient status in rural primary school children ; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection . The burden of micronutrient deficiency ( anaemia , iron and vitamin A ) and stunting in this study population was low and , coupled with the restricted duration of the intervention ( 16 weeks ) , might have limited the impact of the interventions To investigate the relationships between helminth infections and iron status among school-aged children , 1,115 Tanzanian children in grade s 2 through 5 were r and omly assigned to treatment or control groups . The children in the treatment group were screened for infection with Schistosoma haematobium and hookworm at baseline , 3 months , and 15 months ; infected children were given albendazole against hookworm and praziquantel against schistosomiasis . The control group received a placebo and did not undergo parasitological screening until 15 months after the baseline . Hematological variables were compared between the treatment and control groups . The main results were , first , that the hemoglobin concentration significantly improved after treatment for hookworm ( p < .001 ) by 9.3 g/L in children treated for hookworm only and by 8.8 g/L in children treated for hookworm and schistosomiasis . The ferritin concentration also improved in children treated for schistosomiasis ( p = .001 ) or hookworm ( p = .019 ) . Second , a longitudinal analysis of the data from the children in the control group showed that hookworm and schistosomiasis loads were negatively associated with hemoglobin and ferritin concentrations . Moreover , ferritin concentrations increased as C-reactive protein levels increased . Overall , the results showed that anthelmintic treatment is a useful tool for reducing anemia in areas with high hookworm and schistosomiasis endemicity . The empirical relationship between ferritin and C-reactive protein indicated that simple procedures for adjusting cutoff points for the use of ferritin as an indicator of low iron stores were unlikely to be useful in this population Stool specimens from a sample of schoolchildren at six schools in Kweneng District were examined for hookworm infection , using the brine flotation method . Necator americanus was the only hookworm identified . The western part of the District forms part of the Kalahari Desert , and in four villages here 90 % , 88 % , 88 % and 86 % of the children were infected . In two villages in the eastern non-desert part , only 13 % and 9 % were infected . Most infections were light . There was no significant correlation between severity of infection and anaemia . In one school ( 228 pupils ; 86 % infected with hookworm ) , half the children were treated with tetrachloroethylene ( 0.1 ml/kg , maximum 5 ml ) and the other half with placebo . Two weeks after treatment the prevalence of infection were 28 % and 75 % respectively ( p less than 0.001 ) , and five months after treatment 51 % and 69 % ( p less than 0.05 ) . Measured over the five-month period there were no significant changes in haemoglobin and nutritional status ( weight/height ) . Based on the results of the survey , a hookworm mass treatment programme was not recommended The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children ( age 9–12 years ) in Jamaica , using a double-blind placebo-controlled protocol . Results were evaluated by using a forward-stepwise multiple linear regression . Removal of worms led to a significant improvement in tests of auditory short-term memory ( p < 0.017 ; p < 0.013 ) , and scanning and retrieval of long-term memory ( p < 0.001 ) . Nine weeks after treatment , there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function . It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy OBJECTIVE To study the clinical efficacy and the incremental cost-effectiveness of albendazole in improving the nutritional status of pre-school children . DESIGN Single blind , placebo-controlled trial with child as the unit of r and omization . SETTING In the Anganwadi centers of the Integrated Child Development Services situated in the urban slums of Lucknow , North India . METHODS Thirty-two Anganwadi centers were r and omly selected for the trial . Included were registered resident children between 1.5 to 3.5 years of age with informed and written parental consent . The intervention group received 600 mg of albendazole powder every six months while the placebo group received same quantity of calcium powder . Enrolled children were contacted once in six months from January 1995 to 1997 and given treatment . The outcome measure were change in the proportion of underweight ( weight for age < -2.00z ) , stunted ( height for age < -2.00z ) children and the cost per child prevented from becoming stunted . RESULTS There were 610 and 451 children in the albendazole and placebo groups , respectively . Mean age at recruitment was 31.8 months ( SD : 9.7 ) . Follow-up and compliance in both the groups was > 95 % . During the 2 year follow-up , the proportion of stunted children increased by 11.44 % and 2.06 % in the placebo and albendazole groups , respectively , and the difference was 9.38 % ( 95 % CI 6.01 % to 12.75 % ; p value < 0.0001 ) . Direct fecal smear was positive for the ova of ascaris in 41.2 % and 55.3 % children in the albendazole and placebo groups , respectively at the end of the study ( p value < 0.001 ) . The annual family expenditure on illness in the recruited child was Rs . 743 ( SD : 662 ) and Rs . 625 ( SD : 609 ) in the albendazole and the placebo groups , respectively . The incremental cost-effectiveness ratio was Rs 543.00 for each case of stunting prevented with albendazole . There was no difference in the various morbidity or cognitive performance , as judged by the revised Denver prescreening question naire , in both the groups at enrollment as well as at the end of the study . CONCLUSIONS Six monthly albendazole reduces the risk of stunting with a small increase in the expenditure on health care from the payer 's perspective . Larger trials are needed to study the effect of albendazole on prevention of stunting , cognitive functions and all-cause childhood mortality A 2-year investigation , consisting of a controlled , non-blind , 3-monthly chemotherapeutic intervention trial , based on transmission dynamics of Ascaris lumbricoides infection , was undertaken to prove or refute the role of A. lumbricoides as a contributor to childhood malnutrition . The study involved 1206 children aged 2 - 12 years in 21 villages in Myanmar [ Burma ] starting in August 1984 . The intervention and non-intervention villages were comparable regarding almost all the important baseline variables , including prevalences of Ascaris infection ( 80.8 vs 83.0 % ) and of malnutrition of grade 2 and above for height-for-age ( 58.4 vs 55.8 % ) and for weight-for-age ( 48.2 vs 47.8 % ) . The intensity of Ascaris infection was related to the degree of malnutrition . A significant increment of height gain was found , starting after the 6th month , and of weight gain after the 24th month , of the study among the treated 2 - 10 years old children when compared with the non-treated ones . By the end of 24 months , the height and weight gains per child were 0.65 cm and 0.93 kg respectively . Lesser increments in height-for-age and weight-for-age were also observed after successive treatments among the treated children with initially higher mean worm burdens . The findings are discussed in the context of causal relationship between ascariasis and malnutrition in children OBJECTIVES To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal . To assess the South African government 's parasite control policy . METHODS The study recruited 268 school children , aged 8 to 10 , and r and omly allocated them into treatment and placebo groups ( treatment consisted of a single dose of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg ) ) . Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline ( prior to treatment ) and 16 weeks post treatment . Two weeks after treatment prevalence and intensity were again measured for an approximate 50 % sub- sample of the children to investigate efficacy of treatment . An analysis of the South African government 's policies concerning parasite control is assessed in the light of these epidemiological findings . RESULTS Low levels of both stunting and wasting were observed throughout the study ( approximately 10 % and 1 % , respectively ) , but did not vary significantly across either treatment group or time period ( P > 0.50 ) . At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5 % , Trichuris trichiura 51.9 % and Schistosoma haematobium 22.3 % . These prevalences declined significantly to 4.7 % ( P < 0.0005 ) , 38.0 % ( P < 0.03 ) , and 3.3 % ( P < 0.0002 ) , respectively , 16 weeks post treatment . The majority of infections observed at baseline were of light intensity , namely A. lumbricoides ( 50 % ) , T. trichiura ( 80 % ) and S. haematobium ( 100 % ) , and following treatment these levels were reduced significantly ( P < 0.0001 , P < 0.05 and P < 0.005 , respectively ) . The levels of both prevalence and intensity in the untreated group remained constant . The cure rates over the first two weeks of the study were found to be 94.4 % for A. lumbricoides , 40 % for T. trichiura and 72.2 % for S. haematobium . CONCLUSION The benefits of targeted , school-based treatment in reducing the prevalence and intensity of infection supports the South African government 's focus of using school-based interventions as part of an integrated parasite control programme . These strategies and programmes are consistent with recommendations of the World Health Organization ( WHO ) and The United Nations Children 's Fund ( UNICEF ) The effects of mild to moderate infections of Trichuris trichiura on cognitive functions were investigated in Jamaican children aged 7 to 10 years . In all , 189 infected children and 100 uninfected classmates were studied . The infected children were r and omly assigned to receive treatment ( albendazole ) or a placebo . All children were given cognitive tests on enrolment and 14 weeks later . These included verbal fluency ( generation of ideas ) , digit span ( working memory ) , number choice ( speed of processing of visual stimuli ) , visual search ( sustained attention ) and a French Vocabulary test ( paired-associate learning ) . At baseline , the infected children had lower scores than the uninfected ones in fluency ( P = 0.01 ) , search ( P = 0.02 ) and French ( P = 0.01 ) . Treatment effects were examined among infected children and there was no significant treatment effect for any of the tests . However , there was a significant treatment by weight-for-age interaction in fluency ( P < 0.05 ) . The children with low weight-for-age ( Z-score < -1 ) improved with treatment while there was no improvement with treatment among the other children . We concluded that treatment of children with mild to moderate T. trichiura infections using albendazole produces little benefit in cognition if they are adequately nourished ; however , undernourished children are more likely to benefit Objective : To assess the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol concentration , using schools as a health delivery system . Study area and population : From 19 primary schools in Bondo District , western Kenya , 977 children between 9 and 18 y were included in the trial . The 644 ( 65.9 % ) children on whom baseline serum retinol was available were included in this study . Design : A r and omised , placebo-controlled , double-blind , two-by-two factorial trial on the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol after 8 months . Intervention : Single treatment with albendazole ( 600 mg ) and praziquantel ( 40 mg/kg of body weight ) and daily multi-micronutrient supplementation with tablet containing 1000 µg vitamin A. Results : Micronutrient supplementation ( 0.08 µmol/l , 95 % CI 0.01 , 0.14 ; P=0.025 ) , but not treatment ( 0.03 µmol/l , 95 % CI −0.04 , 0.10 ; P=0.38 ) , increased serum retinol . However , treatment did increase serum retinol in S. mansoni-infected ( 0.09 , 95 % CI 0.02 , 0.16 ; P=0.009 ) , but not in uninfected children ( −0.07 , 95 % CI −0.18 , 0.03 ; P=0.18 ; interaction , P=0.01 ) . Similarly , reduction in egg output of S. mansoni , but none of the geohelminth , was a predictor , corresponding to a 0.008 µmol/l ( 95 % CI 0.00002 , 0.02 ; P=0.049 ) increase in serum retinol per 100 epg reduction . Interestingly , interactions were found between age and sex ( P=0.046 ) , and malaria parasitaemia and sickle cell phenotype ( P=0.04 ) . Conclusion : Multi-micronutrient supplementation and reduction in S. mansoni egg output increased serum retinol , irrespective of initial serum retinol . Sponsorship : The Danish International Development Assistance OBJECTIVE To determine whether successful deworming for 6 months in children with high levels of Ascaris improves physical growth . SUBJECTS Two hundred twenty-eight children ( mean age , 9.7 years ) in a highl and Indian town in Guatemala . DESIGN Children were r and omly assigned to receive albendazole or placebo at baseline and 12 weeks . Children and field workers were both blind to the group assignment . OUTCOME MEASURES Children 's heights , weights , and mid-upper-arm circumferences were measured at baseline and 12 and 24 weeks . Fecal egg counts were taken at 0 , 2 , 12 , 14 , and 24 weeks to estimate the helminth burden ( eggs per gram of feces [ epg ] ) . RESULTS Baseline helminth prevalences were Ascaris , 91 % , and Trichuris , 82 % . Ascaris intensities were high : half of the children had moderate burdens ( 10 000 to 50 000 epg ) , and 25 % had heavy burdens ( > 50 000 epg ) . Trichuris burdens were light ( 72 % < 1000 epg ) . The albendazole and placebo groups did not differ at baseline in epg , age , anthropometry , or socioeconomic status . The two rounds of treatment successfully reduced the Ascaris burdens but had less effect on Trichuris . At 6 months the treatment group showed a small gain in weight ( 0.18 kg ) compared with the placebo group but no improvement in height or mid-upper-arm circumference . CONCLUSIONS The successful removal of ascaris in a population of school-aged children with relatively high loads may have modest effects on weight gain . Ascaris is one of the most common infections in school-aged children , but its effect on the host may be less than that of other helminths We studied physical fitness with the Harvard step test ( HST ) , in primary schoolboys infected with hookworm ( 91 % baseline prevalence ) , Trichuris trichiura ( 94 % ) and Ascaris lumbricoides ( 39 - 40 % ) who received a single 400 mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om to placebo or albendazole groups , treated , and re-examined 7 weeks later . The 2 groups did not differ significantly before treatment in age , anthropometry , haemoglobin levels , prevalence or intensity of the 3 helminth infections , or in initial HST fitness scores and heart rates . Seven weeks after treatment , the albendazole group ( n = 18 ) exhibited significant improvements in fitness scores and heart rates at 1 , 2 , 3 , and 4 min after the HST while in the placebo group ( n = 15 ) these quantities had not changed significantly . After treatment , the albendazole group had significant decreases in the logarithmic egg counts for hookworm ( 80 % reduction in arithmetic means ) and A. lumbricoides ( 100 % reduction ) ; T. trichiura egg counts did not change significantly . The placebo group showed a borderline increase in the logarithms of hookworm egg counts and no significant change in T. trichiura and A. lumbricoides egg counts . Multiple regression analysis showed that the significant linear predictors of increase in HST score after treatment were decrease in resting heart rate after treatment , and decreases in hookworm egg counts and logarithms of A. lumbricoides egg counts after treatment . We conclude that single dose treatment with albendazole , despite continual exposure to reinfection , can allow improved physical fitness in schoolboys in areas where soil-transmitted helminths and protein-energy malnutrition are highly prevalent An 18-month study was conducted from February 1989 to August 1990 to examine the effect of regular deworming on child growth and nutritional status . A sample of 1402 children , from 2 to 6 years old , were divided into a treatment group and a control group . The 688 children in the treatment group received a 500 mg single dose of mebendazole , while the 714 children in the control group were given a placebo . Height , weight and mid-upper arm circumference ( MUAC ) were measured on monthly household visits . Growth was measured in terms of the change in height-for-age , weight-for-age , weight-for-height and MUAC over 18 months . The initial prevalence of infection was estimated from a r and om sample of 96 children ( 49 treated , 47 control ) . The initial overall prevalence of Ascaris lumbricoides , Trichuris trichiura and hookworm was 71 , 44 and 10 % respectively . The final prevalence of infection , estimated from a r and om sample of 265 children , was A. lumbricoides 6 % , T. trichiura 6 % and hookworm 2 % in the mebendazole group compared with 64 , 18 and 19 % respectively in the placebo group . Despite the successful treatment of helminths , there was no significant improvement in the growth of treated children compared with their untreated counterparts in terms of the change in z-scores of height-for-age , weight-for-age , weight-for-height and MUAC . The factors which may have contributed to this outcome are discussed Appetite and growth were studied in primary schoolboys ( 6 - 10 years ) infected with Ascaris lumbricoides ( 86 % ) and Trichuris trichiura ( 100 % ) who received a single dose of pyrantel pamoate ( which has little or no effect on Trichuris trichiura ) or a placebo . Boys were examined , allocated at r and om by descending Ascaris egg count to pyrantel ( PR , n = 36 ) or placebo ( PL , n = 36 ) groups , treated , and re-examined 3 and 7 weeks later . The 2 groups did not differ significantly before treatment in helminth infections , appetite , or growth . Three and 7 weeks after treatment , the PR group exhibited significantly greater increases than did the PL group in weight ( 0.2 kg and 0.4 kg more , respectively ) and percentage weight-for-age ( 0.6 % and 1.7 % points more , respectively ) . Appetite increased significantly in the PR group at 3 and 7 weeks ( P < 0.0005 and P < 0.01 , respectively ) but not in the PL group . The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks ( both P < 0.0001 ) but not in the PL group . We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent Abstract Objective To estimate the effectiveness of delivering an anthelmintic through a community child health programme on the weight gain of preschool children in Ug and a. Design Cluster r and omised controlled trial . Setting Eastern Ug and a. Participants 48 parishes participating in a new programme for child health : 24 offered children an additional service of anthelmintic treatment . The outcome is based on measurements from 27 995 children . Intervention Treatment of children aged between 1 and 7 years with 400 mg albendazole added to st and ard services offered during child health days over a three year period . Main outcome measure Weight gain . Results The provision of periodic anthelmintic treatment as a part of child health services in Ug and a result ed in an increase in weight gain of about 10 % ( 166 g per child per year , 95 % confidence interval 16 to 316 ) above expected weight gain when treatments were given twice a year , and an increase of 5 % when the treatment was given annually . Conclusion Deworming of preschool children in Ug and a as part of regularly scheduled health services seems practical and associated with increased weight gain Intestinal helminths are among the most common infections in school-age children . Of 246 children , aged 7 - 12 years , attending school in rural Guatemala , 91 % carried Ascaris lumbricoides and 82 % carried Trichuris trichiura . These children were r and omly assigned to receive either albendazole or placebo at 0 and 12 weeks in a ' double-blind ' study of the effects of deworming on indicators of school performance . Albendazole successfully rid the children of Ascaris but it was less effective against Trichuris . The children 's performance in tests of reading and vocabulary were measured at 0 and 24 weeks , the Peabody picture vocabulary test was given at 24 weeks , and attendance was measured throughout the school year . Comparison of the treated and placebo groups showed no positive effect of deworming . The treated children were largely free of Ascaris for at least 6 months , but during that period we could not detect any improvement in reading , vocabulary , or attendance . The effects of being Trichuris-free were not examined because of the limited effectiveness of albendazole against this worm at the dosage used To access the effectiveness of the treatment of soil-transmitted helminthiasis ( STH ) on the growth of primary school children , 353 children were block stratified to receive either mebendazole plus pyrantel oxantel pamoate every three months or a placebo . The children were followed for two years with 89 % completing the trial . Follow-up stools indicated that the treatment was efficacious for ascariasis and trichuriasis . There was virtually no hookworm infection . The children were malnourished as measured by the number below -2 SD of height and weight st and ards . There was no difference in height or weight between the treatment and control groups by sex initially or at the end of two years of follow-up . The treatment of Ascaris and Trichuris had no effect on growth parameters . The effect of STH on growth may be mediated through hookworm infections BACKGROUND Epidemiological studies have shown inverse associations between geohelminth ( intestinal helminth ) infection and atopy , leading to the suggestion that geohelminths might protect against allergy . Periodic deworming of school children with anthelmintics is a widely implemented intervention and has raised concerns that such programmes could increase allergy . We investigated the effect of repeated anthelmintic treatments with albendazole over 12 months on the prevalence of atopy and clinical indices of allergy . METHODS We did a cluster-r and omised controlled trial in schoolchildren from 68 rural schools . Children were r and omly assigned by school to either albendazole ( 34 schools , 1164 children ) every 2 months for 12 months , or to no intervention ( 34 schools , 1209 children ) . The intervention schools received a total of seven albendazole treatments . The primary outcome was atopy at 12 months ( allergen skin-test reactivity ) , and analysis was by intention-to-treat for whole-school analyses and per protocol for children . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N61195515 . FINDINGS Data for analysis were available for all schools and from 67.4 % ( 784 of 1164 ) and 70.1 % ( 848 of 1209 ) of children in albendazole and no-treatment groups , respectively . Albendazole treatment caused large reductions in geohelminth prevalence over the study period ( adjusted odds ratio 0.13 , 95 % CI 0.09 - 0.19 , p<0.001 ) , but there was no evidence that treatment was associated with an increase in atopy prevalence ( 0.97 , 0.68 - 1.39 , p=0.862 ) , or clinical allergy ( wheeze , 1.07 , 0.54 - 2.11 , p=0.848 ) in the albendazole compared with the no-treatment group . INTERPRETATION We saw no increase in the prevalence of atopy or clinical allergy associated with albendazole treatment . Deworming programmes for schoolchildren are unlikely to be accompanied by an increase in allergy This study was undertaken to measure the impact of periodic deworming with albendazole on growth status and incidence of diarrhoea in children aged 2 - 5 years in an urban setting in India and to assess the feasibility of local health workers implementing the procedures involved . This was a double-blind , placebo-controlled , r and omized , community-based intervention trial with 702 children r and omly allocated to receive either albendazole or placebo . The two study groups received two doses of albendazole ( 400 mg ) or placebo six months apart . Mean weight increased significantly in the albendazole group compared to the control group at three months , six months and nine months following treatment ( P<0.01 , P<0.01 and P<0.001 respectively ) . The albendazole group also experienced fewer episodes of diarrhoea than their control counterparts ( relative risk 1.3 , 95 % CI 1.07 - 1.53 ) with a 28 % reduction . The health workers administered the correct dosage satisfactorily and there were no adverse effects . Thus , periodic mass deworming with albendazole would seem to be a safe and effective method that could be adopted at the community level or as an integral part of school health services and could be expected to improve growth and reduce the incidence of diarrhoea in children This r and omized double blind community trial was conducted on Ascaris infested children ( n = 85 ) aged 2 to 12 years and was aim ed to study the impact of deworming on nutritional status , in an urban slum of Dhaka , Bangladesh . The change of weight gain was significantly higher in children given anthelmintics than those given placebo ( 0.92 kg vs. 0.54 kg ) . A multiple linear regression model shows that after controlling sex , deworming and height were positively correlated while age and weight were negatively correlated with weight change We studied the growth of primary schoolchildren with hookworm ( 87 % ) , T. trichiura ( 97 % ) , and A. lumbricoides ( 49 % ) who received a single 400 mg dose of albendazole or an identical placebo . Children were allocated at r and om to placebo ( PL , n = 72 ) or albendazole ( A , n = 78 ) groups , treated , and re-examined 6 months later . The A group gained significantly more than the PL group in weight ( 1.3 kg ) , percent weight for age ( 4.5 % age points ) , percent height for age ( 0.5 % age points ) , percent weight for height ( 4.3 % age points ) , percent arm circumference ( 2.9 % age points ) , and in triceps and subscapular skinfold thicknesses ( 1.2 mm ) . The PL group showed significant decreases between exams in percent weight for age , percent height for age , percent weight for height , percent arm circumference for age , and skinfold thicknesses for age . The A group had highly significant increases ( P less than 0.0002 ) in all of these parameters except height for age . From Exam 1 to 2 , the A group exhibited decreases ( P less than 0.0002 ) in geometric means eggs per gram of feces ( epg ) : for hookworm , means = 1,183 epg at Exam 1 vs. 136 epg at Exam 2 ( 67 % egg reduction ) ; for T. trichiura , means = 2,857 epg at Exam 1 vs. 1,061 epg at Exam 2 ( 28 % egg reduction ) ; and for A. lumbricoides , means = 86 epg at Exam 1 vs. 2 epg at Exam 2 ( 91 % egg reduction ) . The PL group had a borderline increase in geometric means hookworm egg count , no significant change in T. trichiura egg count , and a small but significant decrease in A. lumbricoides egg count . Decreases in intensities of all infections were significant predictors of growth improvement . Hookworm egg count entered the equations for all 6 measurements , and A. lumbricoides and T. trichiura entered 4/6 equations . Single dose treatment with albendazole , despite continual exposure to infection , can permit improved growth rates in areas where intestinal helminths and protein-energy malnutrition are highly prevalent A r and omized controlled trial in KwaZulu-Natal ( South Africa ) of 428 primary -school pupils ( stratified into 6 groups by age , sex and intervention ) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year ( 1996/97 ) . Half the pupils received iron supplementation ( ferrous fumarate 200 mg weekly for 10 weeks ) . Pupils received 2 anthelmintic regimens , either ( i ) albendazole 400 mg plus praziquantel 40 mg/kg or ( ii ) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or ( iii ) placebo . Baseline prevalences of Ascaris 55.9 % , Trichuris 83.6 % , hookworm spp . 59.4 % , were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4 % ( P < 0.005 ) , Trichuris 61.5 % ( NS ) , hookworm spp . 0 % ( P < 0.005 ) , and for triple-dose albendazole treatment to Ascaris 14.8 % ( P < 0.005 ) , Trichuris 25.0 % ( P < 0.01 ) , hookworm 0 % ( P < 0.005 ) . Schistosoma haematobium 43.4 % was reduced among treated groups to 8.3 % ( P < 0.005 ) . There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment . Twelve months after treatment there was a significant increase in haemoglobin levels ( P = 0.02 ) among pupils receiving triple-dose albendazole , praziquantel and ferrous fumarate ; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron . Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris , hookworm spp . and S. haematobium infections ( P < 0.05 ) . Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg ( P = 0.002 ) . In areas with schistosomiasis , hookworm infection and high prevalence of Trichuris infection , combination treatment with praziquantel , triple-dose albendazole , plus iron supplementation , is likely to improve pupils ' health and haemoglobin levels Three hundred forty-one Tanzanian preschool children were r and omly assigned to levamisole or placebo treatment given at three-month intervals . Weights and heights were measured at the tri-monthly treatment visits for a period of one year . Among the 273 children who were seen and weighed at the one-year follow-up visit , the rate of weight gain was 8 per cent greater for those receiving levamisole than for placebo-treated controls ( p = .06 ) . In 78 children known to be infected with Ascaris at baseline , the rate of weight gain was 21 per cent greater in children treated with levamisole than in those receiving placebo ( p = .03 ) . The rate of height gain was no different for treatment and placebo groups Trichuris trichiura is extremely prevalent worldwide and there is concern that this geohelminth may affect the cognitive function of children in developing countries . A r and om-controlled , double-blind , treatment trial was conducted in Jamaican children with light to moderate infections . This was part of a research programme involving several studies in Jamaica . Ninety-seven subjects , each with a minimum of 1200 T. trichiura eggs/g faeces , were r and omly assigned to placebo ( N = 48 ) or treatment ( N = 49 ) groups . Each pair of infected children was matched with an uninfected classmate ( N = 48 ) . All children were given seven cognitive function tests : French-learning ; digit spans ( forwards and backwards ) , Corsi block span ; fluency ; picture search ; and silly sentences . Albendazole was given to the treatment group and the other groups received a placebo . Three months later , these treatments were repeated , and the cognitive function battery was given again . On pre-test , the infected groups performed significantly poorer only in the silly-sentence test ( analysis of variance F-value = 8.17 ; two degrees of freedom ; P < 0.001 ) . There was no significant improvement with treatment in any of the tests . Taking into account these findings and those of the other Jamaican studies , it is therefore probable that light to moderate Trichuris infections have little effect on cognitive functioning in school children who have adequate nutritional status |
579 | 18,855,813 | Overall , active substance use was associated with poor adherence , as well as depression and low social support .
Higher adherence was found in patents receiving care in structured setting s ( e.g. directly observed therapy ) and /or drug addiction treatment ( especially substitution therapy ) .
While lower than other population s-especially among users of stimulants , incarcerated DU and patients with psychiatric comorbidities-adherence to HAART among HIV-positive DU can be achieved .
Better adherence was identified among those engaged in comprehensive services providing HIV and addiction treatment with psychosocial support | AIMS Adherence to highly active antiretroviral therapy ( HAART ) is a key predictor of survival for human immunodeficiency virus (HIV)-infected people .
Suboptimal adherence among marginalized population s such as HIV-positive drug users could be associated with clinical failure and the emergence of viral resistance .
OBJECTIVE To conduct a systematic review of studies assessing adherence to HAART among HIV-positive drug users ( DU ) and identify factors associated with non-adherence to HIV treatment . | Objective : To identify the effects of substance abuse status ( active , former , and never ) on utilization of highly active antiretroviral therapy ( HAART ) , medication adherence , and virologic and immunologic responses to therapy . Design : Prospect i ve cohort study of 764 HIV‐1‐infected patients who attended an urban HIV clinic and participated in a st and ardized interview . Main Outcome Measures : Past utilization of HAART , self‐reported nonadherence with antiretroviral therapy , and changes in HIV‐1 RNA level and CD4 + lymphocyte count relative to prior peak and nadir , respectively . Results : Forty‐four percent of active drug users failed to utilize HAART compared with 22 % of former drug users and 18 % of non‐drug users ( p < .001 for both comparisons ) . Among participants who were taking antiretroviral therapy when interviewed , active drug users were more likely to report medication nonadherence ( 34 % vs. 24 % of nonusers and 17 % of former users ) , had a smaller median reduction in HIV‐1 RNA from baseline ( 0.8 log10 copies/ml vs. 1.7 in nonusers and 1.6 in former users ) , and had smaller median increases in CD4 + lymphocyte count from baseline ( 65 cells/mm3 vs. 116 in nonusers and 122 in former users ) ( p < .05 for all comparisons with active users ) . Conclusions : Active drug use was strongly associated with underutilization of HAART , nonadherence , and inferior virologic and immunologic responses to therapy , whereas former drug users and non‐drug users were similar in all outcomes . Effective strategies are needed that integrate HIV‐1 and substance abuse treatments Directly administered antiretroviral therapy ( DAART ) is one approach to improving adherence to among human immunodeficiency virus (HIV)-infected drug users . We evaluated the essential features of a community-based DAART intervention in a r and omized , controlled trial of DAART versus self-administered therapy . Of the initial 72 subjects , 78 % were racial minorities , and 32 % were women . Social and medical comorbidities among subjects included homelessness ( 35 % of subjects ) , lack of interpersonal support ( 86 % ) , major depression ( 57 % ) , and alcoholism ( 36 % ) . At baseline , the median CD4 + cell count was 403 cells/mL and the median HIV-1 RNA load was 146,333 copies/mL ( log10 5.31 copies/mL ) . During the prior 6 months , 33 % of subjects had missed a medical appointment , and 47 % had visited an emergency department . Although most subjects ( 67 % ) preferred to take their own medications , 76 % would accept DAART if it were made compulsory . A methadone clinic was the DAART venue acceptable to the fewest subjects ( 36 % ) , and a mobile syringe-exchange program was acceptable to the most subjects ( 83 % ) . Adherence was higher for supervised than for unsupervised medication administration ( P<.0001 ) , a finding that supports use of daily supervision of once-daily regimens . Moreover , DAART should incorporate enhanced elements such as convenience , flexibility , confidentiality , cues and reminders , responsive pharmacy and medical services , and specialized training for staff To evaluate the impact of injection drug users ( IDUs ) adherence on effectiveness of highly active antiretroviral therapy ( HAART ) , repeated measures of plasma viral load and CD4 + counts before HAART initiation and at last visit in the cohort were studied . Data were collected by means of patient 's face-to-face and self-administered question naires about adherence to HAART during the week prior to the last visit . Of a total of 119 patients treated with HAART , undetectable viral load was obtained for 55 patients ( 46.2 % ) ( G3 ) ; 34 patients ( 28.6 % ) ( G2 ) had a viral load decline > 0.5 log copies/ml but still detectable viral load at last visit in the cohort , while 30 patients ( 25.2 % ) ( G1 ) had no decline or decline ≤ 0.5 log copies/ml . Proportion of 100 % adherent patients was significantly higher in G3 ( 83.6 % ) than in G2 ( 64.7 % ) and G1 ( 56.7 % ) . In spite of differences in virological success and adherence , mean increase in CD4 + counts was similar in G3 ( 123 ± 160 counts/mm3 ) and G2 ( 143 ± 147 ) while no immunological improvement was observed in G1 . For the sub-groups of patients whose limited adherence has implied virological failure but did not impede short-term immunological reconstitution following HAART initiation , decision to switch HAART regimens could be delayed until interventions for improving future adherence have been carried out Objective To assess the temporal association of changes in substance abuse with antiretroviral therapy use and adherence , HIV-1 RNA suppression , and CD4 cell count changes in patients attending an urban clinic . Design Prospect i ve cohort study . Methods Six-hundred and ninety-five HIV-1-infected individuals , who completed two or more semi-annual st and ardized surveys and in whom antiretroviral therapy was indicated , were included in the analysis . Surveys addressed antiretroviral therapy use and adherence , and use of illicit drugs and alcohol . Substance abuse was defined as active heroin , cocaine , or heavy alcohol use in the 6 months preceding survey . The units of analysis were consecutive pairs of surveys ( couplets ) in individual participants . Couplets in which participants denied substance abuse in both surveys were compared to couplets in which participants switched from non-use to substance abuse , and couplets in which participants reported substance abuse in both surveys were compared to couplets where participants switched from substance abuse to non-use . Results Switching from non-use to substance abuse was strongly associated with worsening antiretroviral therapy use and adherence , less frequent HIV-1 RNA suppression , and blunted CD4 cell increases , compared to remaining free of substance abuse . Alternatively , switching from substance abuse to non-use was strongly associated with improvements in antiretroviral therapy use and adherence , and HIV-1 treatment outcomes , compared to persisting with substance abuse . Conclusions This longitudinal study highlights the dynamic nature of substance abuse and its temporal association with the effectiveness of HIV-1 treatment in patients attending an inner-city clinic This study assesses changes in quality of life ( QoL ) over time among HIV-infected individuals receiving antiretroviral therapy ( ART ) and evaluates how this relates to ART adherence . Prospect i ve , longitudinal data were examined from 1050 participants in two large , r and omized , multi-centre antiretroviral clinical trials . QoL was assessed by the SF-12 ; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report . Participants included 20 % women , 53 % African Americans , 16 % Latinos ; mean age was 39 years ; mean baseline CD4 + cell count 230 cells/mm3 ; 89 % were ART-naïve at entry . Baseline physical and mental health summary QoL scores were 45.4 and 42.9 , comparable to scores reported in other advanced HIV population s. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens , and persisted for 12 months . Participants reporting 100 % ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence , particularly if 100 % adherence was consistent ( p<0.001 ) . Those with at least 80 % ART adherence had smaller gains in QoL at 12 months when compared to baseline , while those with < 80 % adherence had worsening of QoL. In this analysis , ART adherence was associated with improved QoL , particularly if adherence was sustained Improved therapeutic strategies , including the introduction of protease inhibitors , have led to a striking decrease in HIV-related morbidity and mortality ( 1 , 2 ) . It is widely believed that adherence to an antiretroviral regimen is central to the likelihood that a patient will derive sustained benefit from therapy ( 3 , 4 ) . Conventional wisdom holds that two groups of patients are currently experiencing clinical and virologic failure . The first group consists of patients who have received multiple different antiretroviral drugs over a prolonged period of time and who may be infected predominantly with HIV strains that are resistant to multiple drugs . The second group comprises patients who adhere poorly to their antiretroviral regimen . The two groups are not mutually exclusive : Patients with suboptimal adherence may be more likely to have antiretroviral drugresistant HIV infection . The potential public health importance of adherence to therapy in prevention of transmission of drug-resistant virus has also been emphasized ( 5 ) . Patients with suboptimal adherence to antiretroviral therapy and poor adherence to use of safer-sex practice s , such as use of condoms , may infect others with their own antiretroviral drugresistant virus . Anecdotal experience suggests that physicians may be unwilling to prescribe combination antiretroviral therapy to patients whom they perceive to be at high risk for poor adherence ( 6 ) . Given the critical importance of adherence to therapy to patient outcome , secondary prevention of HIV infection , and willingness of providers to prescribe therapy , we prospect ively investigated the association between protease inhibitor adherence and patient outcome , factors related to adherence , and the accuracy of physicians ' prediction of patient adherence . We used a microelectronic monitoring system to assess adherence to antiretroviral therapy . Methods Study Sample The study was conducted at the HIV clinics of the Veterans Affairs Medical Center , Pittsburgh , Pennsylvania , and University of Nebraska Medical Center , Omaha , Nebraska . The HIV physicians at these clinics were primary care providers for the study patients . Each site also had a dedicated HIV nurse coordinator . From August 1997 to March 1999 , we enrolled consecutive patients with HIV infection who were already receiving a protease inhibitor ( experienced patients ) or who were to begin taking a protease inhibitor ( naive patients ) . Exclusion criteria were inability to give informed written consent ; expectation of continued use of a medication organizer to include protease inhibitors ; and residence in a nursing home , jail , or hospice , where medications were dispensed at least daily . Collection of Baseline Data At baseline , a study investigator used medical chart review to complete a 52-item question naire for each patient . The question naire covered demographic information ( age , sex , ethnicity , risk factors for HIV infection , educational and employment status , income ) , medical history ( years known to be HIV infected ; opportunistic infections ; history of schizophrenia , depression , or bipolar affective disorder ) , and medication use ( name , dose , and frequency of all antiretroviral agents , other antimicrobials , and other prescription therapies ) . The enrolling physician assessed use of illegal drugs and nonprescription therapies ( including herbal or alternative therapies ) by interview . Alcohol abuse was assessed by using the CAGE question naire ( cutting down , annoyance with criticism , guilty feelings , and use of eye-opener drinks ) ( 7 ) . Information about use of adherence aids ( such as personal reminders by significant others or timers , alarms , or other devices ) was specifically sought . The investigator asked study patients if they felt that their current symptoms were attributable to HIV infection , the antiretroviral medications , or both . In addition , patients were asked whether they agreed with such health beliefs as Do you think your antiretroviral therapy will make you live longer ? At baseline , each patient completed the Beck Depression Inventory and the General Health Question naire ( 8 , 9 ) , well-vali date d measures of psychiatric morbidity that have been widely used in patients with HIV infection ( 9 - 11 ) . Patients completed the inventories as a written task without the assistance of a physician or clinic nurse . At baseline , we used the following question to elicit a prediction of adherence to protease inhibitor therapy from the patient 's primary HIV physician and clinic nurse : Do you think that the patient is compliant with antiretroviral therapy , that is , taking greater than 80 % of the prescribed doses of antiretroviral medications ? This prediction was made after collection of the baseline information but before actual measurement of adherence using the microelectronic monitoring system had begun . Collection of Follow-up Data Every 3 months for the duration of the study , the study participants were asked whether any of the following had changed since their previous visit : employment , use of alcohol or illegal drugs , residence , attribution of symptoms to the antiretroviral therapy or HIV infection , and changes in medications . Patients completed a new Beck Depression Inventory and General Health Question naire . The primary HIV physician determined whether the patient had developed an opportunistic infection in the past 3 months . Laboratory Testing At baseline and every 3 months for the duration of the study , HIV RNA levels were measured by using the Roche Amplicor System ( Roche Diagnostics , Nutley , New Jersey ) and CD4 lymphocyte sub population assays were performed . Assessment of Adherence Adherence was measured by using the Medication Events Monitoring System ( MEMS ) ( Aprex , Union City , California ) . The MEMS TrackCap system consists of st and ard medication bottles that have a pressure-activated microprocessor in the cap ( 12 ) . The microprocessor records each opening and lists the date , time , and duration of opening . The information on medication dosing is retrieved by scanning the cap over a purpose -built communicator module . The information is then stored in a data base provided by Aprex . Although the MEMS TrackCap system can not prove consumption of the drug by the patient , prolonged deception by patients has been shown to be unlikely ( 13 ) . Patients were provided with a MEMS TrackCap bottle for each prescribed protease inhibitor ( including refrigerated ritonavir capsules ) . Use of the MEMS TrackCaps system was not possible for patients who were prescribed ritonavir from August 1998 onward because ritonavir capsules were no longer available . The patients could use their regular medication organizer for all other medications . The caps were scanned each time the patient presented to the HIV clinic . Patients were specifically instructed not to take extra doses out at any time ( for example , not to take out an extra dose in the morning for consumption at lunchtime ) . Patients were offered small pill bottles that could be easily carried in a coat pocket . Adherence rates were defined as the number of doses recorded by the MEMS TrackCap divided by the total number of doses prescribed during the monitoring period . To evaluate the effect of dosing frequency on adherence , dosing interval errors were defined as medication doses taken at a time other than that prescribed ( that is,<9 hours or>15 hours after the previous dose of a medication prescribed every 12 hours or<5 hours or>11 hours after the previous dose of a medication prescribed every 8 hours ) ( 12 ) . Definitions of Virologic and Clinical Outcomes Virologic failure was defined as an HIV RNA level greater than 400 copies/mL at the last study visit . Changes in CD4 lymphocyte counts were calculated as the difference between the count at the baseline visit and the count at the final study visit . Opportunistic infections were defined according to Centers for Disease Control and Prevention criteria ( 14 ) . Hospitalization for all causes was recorded as the number of nights spent in any acute-care hospital ; nursing homes and drug or alcohol rehabilitation facilities were excluded . Mortality was defined as all-cause mortality at any time during the study period . Statistical Analysis All data was entered into a computerized data base , PROPHET Statistics Version 6.0 ( AB Tech Corp. , Charlottesville , Virginia ) . The chi-square or Fisher test was used to compare categorical variables . Continuous variables were examined by using the t-test or the MannWhitney test . Baseline and follow-up values were compared by using the paired t-test or the Wilcoxon signed-rank test . To examine the relation between two continuous measures , a best-fit line was obtained . The slope of this line was then tested against the null hypothesis of a slope of zero . The Pearson correlation coefficient was also calculated . Cox proportional-hazards regression was used to evaluate the relation between adherence and time to virologic failure . In the Cox model , predictor variables found to be significant ( P<0.1 ) in univariate analysis were added to the model . Logistic regression models were used to assess the effects of multiple variables on adherence . Factors were entered into the regression model if they were found by univariate analysis to be significantly associated ( P<0.1 ) . To analyze time to return of detectable HIV RNA for patients with an undetectable viral load at baseline , KaplanMeier survival curves were computed for less than 95 % adherence and 95 % or greater adherence and were compared by using the MantelCox test . The McNemar test was used to compare the predictions of the clinical nurses and physicians . Ethical Considerations The study was approved by the institutional review boards of the two study centers . Patients were fully informed that their adherence to protease inhibitor therapy was being measured by using the MEMS TrackCap system . Results Patient Characteristics Of 99 patients enrolled in the study , 6 withdrew before follow-up data were collected ( This study 's hypothesis is that human immunodeficiency virus-infected patients in the inner city ( predominantly injection drug users and ethnic minorities ) do not take highly active antiretroviral therapy ( HAART ) as prescribed and that nonadherence leads to virologic failure . A prospect i ve , observational , 3-month study of adherence to HAART was undertaken at an inner-city clinic . There were 40 subjects [ 110 subject-months ] ; 30 were male , 10 were female , 75 % were Hispanic , 23 % were African American , 68 % were injection drug users , and 68 % were receiving triple therapy . At 3 months , adherence , which was determined by use of the Medication Event Monitoring System ( Aprex ) was significantly associated with virologic success : lower virus loads were associated with a rate of adherence of > 80 % ( P<.05 ) . Although nonadherence predicted virologic failure , virologic success was not always predicted by adherence : 11 ( 27.5 % ) of 40 subjects with suboptimal adherence rates ( < 90 % ) had complete virologic suppression Background : Directly administered antiretroviral therapy ( DAART ) is a promising intervention for improving HIV outcomes among active drug users , but the elements associated with successful DAART programs remain largely unknown . This study aim ed to assess the impact of colocated medical , case management , and referral to substance abuse services ( DAART-Plus ) among the subjects receiving DAART as part of a larger r and omized controlled trial comparing DAART with self-administered therapy . Methods : The health services utilization of 72 subjects receiving DAART was analyzed for its impact on changes in HIV-1 RNA levels at 6 months . The primary outcome was virologic success , defined as achieving an HIV-1 RNA level ≤400 copies/mL or a ≥1.0 log10 reduction in HIV-1 RNA level . A second analysis consisted of linear regression assessing the effect of covariates on log10 HIV-1 RNA reduction from baseline to 6 months . Results : In multivariate analyses , achieving virologic success at 6 months was associated with high medical services utilization [ adjusted odds ratio [ AOR ] = 10.0 ( 1.4 , 73.9 ) ; P = 0.02 ] and with the use of case management services [ AOR = 5.8 ( 1.1 , 30.5 ) ; P = 0.04 ] . Both services result ed in a larger reduction in log10 HIV-1 RNA from baseline ( difference in slopes : −0.9 and −1.0 , respectively ; P = 0.02 for both ) . Referral to off-site substance abuse services treatment did not significantly predict either virologic outcome . Conclusions : Among individuals who receive DAART , the utilization of on-site medical and case management services was independently associated with improved virologic outcomes . These results suggest the potential utility of integrating these services into DAART interventions ( DAART-Plus ) targeting HIV-infected drug users with problematic adherence Objectives To assess adherence to highly active antiretroviral therapies ( HAART ) in a cohort of French patients infected by HIV through injection drug use ( IDU ) , and the impact on adherence of buprenorphine ambulatory drug maintenance treatment ( DMT ) which has been widely introduced since 1996 . Design Adherence assessment at first visit after initiation of HAART in the MANIF2000 cohort study . Methods Patient 's face-to-face and self-administered question naires . Univariate and logistic regression adjusted odds ratios ( OR ) to compare characteristics of non-adherent versus adherent patients . Results Of the 164 patients , 34.8 % took less than 80 % of the prescribed HAART doses during the previous week . Decrease in viral load titres after initiation of HAART was significantly lower among non-adherent patients . After adjustment by logistic regression , non-adherence was associated with younger age , alcohol consumption , frequency of negative life-events during the prior 6 months and active drug use . However , IDU in buprenorphine DMT reached higher levels of adherence ( 78.1 % ) than ex-IDU ( 65.5 % ) , although this difference did not reach statistical significance . Conclusion Prescription of buprenorphine DMT may increase adherence to HAART among HIV-infected opiate-dependent patients . Reducing the negative impact of stressful life-events through psychosocial interventions should be considered , even for those who have stopped using drugs Background Behavioral interventions to address the complex medical and HIV risk reduction needs of HIV-seropositive ( HIV-positive ) injection drug users ( IDUs ) are urgently needed . We describe the development of Interventions for Seropositive Injectors— Research and Evaluation ( INSPIRE ) , a r and omized controlled trial of an integrated intervention for HIV-positive IDUs , and the characteristics of the baseline sample . Methods HIV-positive IDUs were recruited from community setting s in 4 US cities . After completing a baseline assessment , participants who attended the first session were r and omly assigned to ( 1 ) a 10-session peer mentoring intervention design ed to improve utilization of HIV care , to improve adherence to HIV medications , and to reduce sexual and injection risk or ( 2 ) an 8-session videotape control . Periodic follow-up for 12 months is ongoing . Results A total of 1161 HIV-positive IDUs completed the baseline assessment , and 966 ( 83 % ) were r and omized . Retention rates are greater than 80 % for all follow-up periods . Approximately 79 % of baseline participants reported a recent medical visit , 49 % were taking highly active antiretroviral therapy , and 19 % had an undetectable viral load . Use of injection and noninjection substances was prevalent , and sexual and injection risks were each reported by more than 25 % of participants . Conclusion There is a need for an integrated intervention for HIV-positive IDUs , and these data show the acceptability of such an approach Objective To examine the relationship between adherence , viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor ( PI ) therapy . Design and setting A cross-sectional analysis of subjects in an observational prospect i ve cohort systematic ally sample d from free meal lines , homeless shelters and low-income , single-room occupancy ( SRO ) hotels . Participants Thirty-four HIV-infected people with a median of 12 months of PI therapy . Main outcomes Adherence measured by periodic unannounced pill counts , electronic medication monitoring , and self-report ; HIV RNA viral load ; and HIV-1 genotypic changes associated with drug resistance . Results Median adherence was 89 , 73 , and 67 % by self-report , pill count , and electronic medication monitor , respectively . Thirty-eight per cent of the population had over 90 % adherence by pill count . Depending on the measure , adherence explained 36–65 % of the variation in concurrent HIV RNA levels . The three adherence measures were closely related . Of 20 genotyped patients who received a new reverse transcriptase inhibitor ( RTI ) when starting a PI , three had primary protease gene substitutions . Of 12 genotyped patients who received a PI without a new RTI , six had primary protease gene substitutions ( P < 0.03 ) . Conclusion A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy . A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression . PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence AIM We examined the association of substance abuse treatment with uptake , adherence and virological response to highly active antiretroviral therapy ( HAART ) among HIV-infected people with a history of alcohol problems . DESIGN Prospect i ve cohort study . METHODS A st and ardized question naire was administered to 349 HIV-infected participants with a history of alcohol problems regarding demographics , substance use , use of substance abuse treatment and uptake of and adherence to HAART . These subjects were followed every 6 months for up to seven occasions . We defined substance abuse treatment services as any of the following in the past 6 months : 12 weeks in a half-way house or residential facility ; 12 visits to a substance abuse counselor or mental health professional ; or participation in any methadone maintenance program . Our outcome variables were uptake of antiretroviral therapy , 30-day self-reported adherence and HIV viral load suppression . FINDINGS At baseline , 59 % ( 205/349 ) of subjects were receiving HAART . Engagement in substance abuse treatment was independently associated with receiving antiretroviral therapy ( adjusted OR ; 95 % CI : 1.70 ; 1.03 - 2.83 ) . Substance abuse treatment was not associated with 30-day adherence or HIV viral load suppression . More depressive symptoms ( 0.48 ; 0.32 - 0.78 ) and use of drugs or alcohol in the previous 30 days ( 0.17 ; 0.11 - 0.28 ) were associated with worse 30-day adherence . HIV viral load suppression was positively associated with higher doses of antiretroviral medication ( 1.29 ; 1.15 - 1.45 ) and older age ( 1.04 ; 1.00 - 1.07 ) and negatively associated with use of drugs or alcohol in the previous 30 days ( 0.51 ; 0.33 - 0.78 ) . CONCLUSION Substance abuse treatment was associated with receipt of HAART ; however , it was not associated with adherence or HIV viral load suppression . Substance abuse treatment programs may provide an opportunity for HIV-infected people with alcohol or drug problems to openly address issues of HIV care including enhancing adherence to HAART PURPOSE This study assessed the utility of a placebo practice trial in determining adherence readiness among drug users . METHOD Participants with histories of drug dependency completed a 2-week practice trial that mimicked HAART ( Phase 1 ) , followed by a 2-week observation of adherence to HAART ( Phase 2 ) for those who began antiretroviral therapy during the study period . The primary measure of adherence was electronic monitoring . RESULTS There were 201 participants enrolled ; 39 % met criteria for current drug dependency . Mean adherence to the practice trial was 67 % . Of the 184 Phase 1 completers , 83 ( 45 % ) initiated HAART prior to the end of the study . Mean adherence to HAART was 74 % , including 33 patients ( 39 % ) with 90+% adherence . Adherence to the practice trial was correlated with antiretroviral adherence ( r = .49 , p < .001 ) , and 90+% adherence to the practice trial was an accurate marker of the " adherence readiness " ( ability to adhere 90+% on HAART ) of 72 % of the participants . In multivariate analyses , practice trial adherence was the best independent predictor of antiretroviral adherence , accounting for 19 % of the explained variance ; other predictors included adherence to recent clinic appointments , cognitive functioning , unstable housing , and adherence self-efficacy . CONCLUSION These findings suggest that a brief placebo practice trial has the potential to provide clinicians and patients with an accurate screening tool for evaluating adherence readiness Abstract This study examined baseline gender differences among HIV-positive methadone maintenance out patients currently prescribed antiretroviral medications . Participants were enrolled in a larger clinical trial , which included a 4-week observation period using electronic monitors to track medication adherence . Contrary to previous literature , no significant differences were detected between men ( n = 42 ) and women ( n = 36 ) on medication adherence or depression . Both groups showed remarkably poor adherence during baseline ( M = 56 % of doses taken on time ) , high overall prevalence of depression ( 47 % ) and illicit cocaine use ( 47 % ) . Women reported significantly more medication side effects ( M = 21.4 vs. 14.9 ) , higher severity of ASI psychiatric problems ( M = 0.50 vs. 0.40 ) , and lower SF-36 health-related quality of life in physical ( M = 42.1 vs. 63.3 ) and emotional functioning ( M = 26.9 vs. 58.9 ) than men . Women tested positive for opioids at higher rates than men ( 53 % vs. 29 % , respectively ) , whereas men were more likely to be positive for benzodiazepines than women ( 26 % vs. 6 % , respectively ) . Findings suggest that gender differences between male and female methadone maintenance patients have relevance to treatment providers . Extensive assessment , specialized medical care and mental health services may be warranted in the treatment of HIV-positive female drug abusers Objectives : To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration , virologic suppression , and the rate of accumulating new drug resistance mutations at different levels of adherence . Methods : Adherence was measured with unannounced pill counts performed at the participant 's usual place of residence in a prospect i ve cohort of HIV-positive urban poor individuals . Two genotypic resistance tests separated by 6 months ( G1 and G2 ) were obtained in individuals on a stable regimen and with detectable viremia ( > 50 copies/ml ) . The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2 . Results : High levels of adherence were closely associated with greater time on treatment ( P < 0.0001 ) and viral suppression ( P < 0.0001 ) in 148 individuals . In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy , the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment ( P = 0.03 ) and pill count adherence ( P = 0.002 ) . Assuming fully suppressed individuals ( < 50 copies/ml ) do not develop resistance , it was estimated that 23 % of all drug resistance occurs in the top quintile of adherence ( 92–100 % ) , and over 50 % of all drug resistance mutations occur in the top two quintiles of adherence ( 79–100 % ) . Conclusion : Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients . Exceptionally high levels of adherence will not prevent population levels of drug resistance |
580 | 26,284,892 | Spine mobilizations combined with glenohumeral stretching and both angular and translational mobilization ( n=1 ) had a superior effect on active ROM compared with sham ultrasound .
CONCLUSIONS Overall , mobilization techniques have beneficial effects in patients with primary AC of the shoulder . | OBJECTIVE To systematic ally review the literature for efficacy of isolated articular mobilization techniques in patients with primary adhesive capsulitis ( AC ) of the shoulder . | Clinical observations have suggested a relationship between shoulder range of movement ( ROM ) and lateral epicondylalgia . This study reports the effect of a single intervention of a mobilization with movement ( MWM ) applied to the elbow , on shoulder rotation ROM in subjects with lateral epicondylalgia . Twenty-three subjects with lateral epicondylalgia were included . In a one-group pretest-post-test design , ROM of shoulder internal and external rotation were measured by goniometer before and after the application of the MWM , of both the unaffected and the affected limbs . Significant differences in pre-intervention external rotation ROM were found between unaffected and affected shoulders of subjects with lateral epicondylalgia , but no significant difference remained post-intervention . It may be concluded that restriction of shoulder rotation ROM is present in patients with lateral epicondylalgia , probably due to a facilitated level of shoulder rotator muscle tone . Shoulder internal and external rotation ROM increases significantly following MWM to the elbow , in subjects with unilateral lateral epicondylalgia . Surprisingly , these ROM increases are also apparent on the ' unaffected ' limb . These findings suggest that the MWM causes a neurophysiologically mediated decrease in resting muscle tone BACKGROUND AND PURPOSE In many physical therapy programs for subjects with adhesive capsulitis of the shoulder , mobilization techniques are an important part of the intervention . The purpose of this study was to compare the effectiveness of high- grade mobilization techniques ( HGMT ) with that of low- grade mobilization techniques ( LGMT ) in subjects with adhesive capsulitis of the shoulder . SUBJECTS One hundred subjects with unilateral adhesive capsulitis lasting 3 months or more and a > or = 50 % decrease in passive joint mobility relative to the nonaffected side were enrolled in this study . METHODS Subjects r and omly assigned to the HGMT group were treated with intensive passive mobilization techniques in end-range positions of the glenohumeral joint , and subjects in the LGMT group were treated with passive mobilization techniques within the pain-free zone . The duration of treatment was a maximum of 12 weeks ( 24 sessions ) in both groups . Subjects were assessed at baseline and at 3 , 6 , and 12 months by a masked assessor . Primary outcome measures included active and passive range of motion and shoulder disability ( Shoulder Rating Question naire [ SRQ ] and Shoulder Disability Question naire [ SDQ ] ) . An analysis of covariance with adjustments for baseline values and a general linear mixed-effect model for repeated measurements were used to compare the change scores for the 2 treatment groups at the various time points and over the total period of 1 year , respectively . RESULTS Overall , subjects in both groups improved over 12 months . Statistically significant greater change scores were found in the HGMT group for passive abduction ( at the time points 3 and 12 months ) , and for active and passive external rotation ( at 12 months ) . A statistically significant difference in trend between both groups over the total follow-up period of 12 months was found for passive external rotation , SRQ , and SDQ with greater change scores in the HGMT group . DISCUSSION AND CONCLUSION In subjects with adhesive capsulitis of the shoulder , HGMTs appear to be more effective in improving glenohumeral joint mobility and reducing disability than LGMTs , with the overall differences between the 2 interventions being small PRINCIPLE A r and omised , comparative prospect i ve clinical trial was planned to compare the early response to different rehabilitation methods for adhesive capsulitis taking into consideration the clinical efficacy and the cost effectiveness of the methods . METHODS Forty patients with adhesive capsulitis were r and omised into two treatment groups . The first group ( CYR ) received the Cyriax approach of deep friction massage and mobilisation exercises three times weekly . The second group ( PT ) had daily physical therapy including hot pack and short wave diathermy application . Both groups concluded their treatments with stretching exercises and were also instructed to a daily home exercise program . The primary end point of the study was to reach 80 % of the normal passive range of motion ( ROM ) of the shoulder in all planes within a period of two weeks . Secondary end points were the overall ROM and pain response ( spontaneous pain , night pain and pain with motion ) to each treatment . RESULTS 19 patients in the CYR group ( 95 % ) and 13 patients in the PT group ( 65 % ) reached sufficient ROM at the end of the second week ( p < 0.05 ) . The improvement in shoulder flexion , inner and outer rotation values and the decrease in pain with motion were significantly better in the CYR group after the first week of treatment . CONCLUSION The Cyriax method of rehabilitation provides a faster and better response than the conventional physical therapy methods in the early phase of treatment in adhesive capsulitis . The method is non-invasive , effective and requires fewer hospital visits for a sufficient early response Seventy-seven patients with idiopathic frozen shoulder syndrome were included in a prospect i ve study to compare the effect of intensive physical rehabilitation treatment , including passive stretching and manual mobilization ( stretching group ) versus supportive therapy and exercises within the pain limits ( supervised neglect group ) . There were no significant differences in age , sex , time elapsed since onset , and disease severity at inclusion . All patients were followed up for 24 months after the start of treatment . In the patients treated with supervised neglect , 89 % had normal or near-normal painless shoulder function ( Constant score > or = 80 ) at the end of the observation period . This end result was reached by 64 % within 12 months . In contrast , of the group receiving intensive physical therapy treatment , only 63 % reached a Constant score of 80 or higher after 24 months . Both the level of the Constant score at the end of the study and the moment a Constant score of 80 or higher was reached confirm that supervised neglect yields better outcomes than intensive physical therapy and passive stretching in patients with frozen shoulder Treatment strategies targeting abnormal shoulder kinematics may prevent pathology or if the pathology develops , shorten its duration . We examined the effectiveness of the end-range mobilization/scapular mobilization treatment approach ( EMSMTA ) in a subgroup of subjects with frozen shoulder syndrome ( FSS ) . Based on the kinematics criteria from a prediction method , 34 subjects with FSS were recruited . Eleven subjects were assigned to the control group , and 23 subjects who met the criteria were r and omly assigned to the criteria -control group with a st and ardized physical therapy program or to the EMSMTA group . Subjects attended treatment sessions twice a week for 8 weeks . Range of motion ( ROM ) , disability score , and shoulder complex kinematics were obtained at the beginning , 4 weeks , and 8 weeks . Subjects in the EMSMTA group experienced greater improvement in outcomes compared with the criteria -control group at 4 weeks ( mean difference=0.2 of normalized h and -behind-back reach ) and 8 weeks ( mean difference=22.4 degrees humeral external rotation , 0.31 of normalized h and -behind-back reach , 7.5 disability , 5 degrees tipping and 0.32 rhythm ratio ) . Similar improvements were found between the EMSMTA group and control group . The EMSMTA was more effective than a st and ardized physical therapy program in a subgroup of subjects who fit the criteria from a prediction method OBJECTIVE To evaluate Mulligan 's technique for relieving pain and improving functional capacity of the shoulder in patients with adhesive capsulitis in the stiffness phase . DESIGN R and omized controlled study . METHODS A total of 40 subjects were r and omly allocated into 2 groups : ( i ) group 1 ( n = 20 ) were treated with hot pack , transcutaneous electrical nerve stimulation , and passive stretching exercises ; ( ii ) group 2 ( n = 20 ) were treated with hot pack , transcutaneous electrical nerve stimulation and Mulligan 's technique . Mulligan 's technique combines the sustained application of a manual " gliding " force to a joint , with the aim of repositioning bone positional faults while enabling concurrent physiological ( osteo-kinematic ) motion of the joint . All cases were evaluated using visual analogue scales for pain , passive and active range of motion , Constant score , Shoulder Disability Question naire , and patient and therapist satisfaction at baseline , after completion of treatment sessions and at the end of 3 months of follow-up . RESULTS Marked improvement was noted in both groups after completion of treatment sessions and at the third month of follow-up compared with baseline . The improvements in outcome measures , namely pain , range of motion , shoulder scores , and patient and physiotherapist satisfaction , were significantly greater in subjects in group 2 , who were treated with Mulligan 's technique . CONCLUSION Mulligan 's technique and passive stretching exercises are both effective in reducing pain , and restoring range of motion and function . However , compared with stretching exercises , Mulligan 's technique led to better improvements in terms of pain , range of motion , shoulder scores , and patient and physiotherapist satisfaction Background Adhesive Capsulitis ( AC ) affects patient of all ages , and stretching protocol s are commonly prescribed for this condition . Dynamic splinting has been shown effective in contracture reduction from pathologies including Trismus to plantar fasciitis . The purpose of this study was to examine the efficacy of dynamic splinting on patients with AC . Methods This controlled , cohort study , was conducted at four physical therapy , sports medicine clinics in Texas and California . Sixty-two patients diagnosed with Stage II Adhesive Capsulitis were grouped by intervention . The intervention categories were as follows : Group I ( Control ) ; Group II ( Physical Therapy exclusively with st and ardized protocol s ) ; Group III ; ( Shoulder Dynasplint system exclusively ) ; Group IV ( Combined treatment with Shoulder Dynasplint and st and ardized Physical Therapy ) . The duration of this study was 90 days for all groups , and the main outcome measures were change in active , external rotation . Results Significant difference was found for all treatment groups ( p < 0.001 ) following a one-way ANOVA . The greatest change with the smallest st and ard deviation was for the combined treatment group IV , ( mean change of 29 ° ) . Conclusion The difference for the combined treatment group was attributed to patients ' receiving the best PT combined with structured " home therapy " that contributed an additional 90 hours of end-range stretching . This adjunct should be included in the st and ard of care for adhesive Capsulitis . Trial Registration Trial Number : OBJECTIVE To determine whether an active physiotherapy program following arthrographic joint distension for adhesive capsulitis provides additional benefits . METHODS We performed a r and omized , placebo-controlled , participant and single assessor blinded trial . A total of 156 participants with pain and stiffness in predominantly 1 shoulder for > or=3 months and restriction of passive motion > 30 degrees in > or=2 planes of movement entered the study , and 144 completed the study . Following joint distension , participants were r and omly assigned to either manual therapy and directed exercise or placebo ( sham ultrasound ) , both administered twice weekly for 2 weeks then once weekly for 4 weeks . Pain , function , active shoulder movements , participant-perceived success , and quality of life were assessed at baseline , 6 , 12 , and 26 weeks . Costs were also collected . RESULTS Both groups improved over time with no significant differences in improvement between groups for pain , function , or quality of life at any time point . Significant differences favored the physiotherapy group for all active shoulder movements ( e.g. , pooled difference in mean change between groups across all time points for total shoulder abduction was 10.6 degrees , 95 % confidence interval [ 95 % CI ] 3.1 , 18.1 ) and participant-perceived success ( pooled relative risk 1.4 , 95 % CI 1.1 , 1.65 ; number needed to treat = 5 ) . Net cost of physiotherapy was $ 136.8 Australian ( 95 % CI -177.5 , 223.1 ) over the 6 months . CONCLUSION Physiotherapy following joint distension provided no additional benefits in terms of pain , function , or quality of life but result ed in sustained greater active range of shoulder movement and participant-perceived improvement up to 6 months OBJECTIVE To determine the efficacy of positioning the affected shoulder in flexion and external rotation to prevent contracture shortly after stroke . DESIGN Prospect i ve , parallel-group , r and omized controlled trial . SETTING Four metropolitan mixed rehabilitation units . PARTICIPANTS A volunteer sample of 36 subjects ( minus 5 dropouts ) , whose mean age was 68 years and had had their first stroke within the past 20 days . INTERVENTIONS The experimental group received two 30-minute sessions a day , 5 days a week , for 4 weeks , during which the affected upper limb was placed in maximum comfortable external rotation and 90 degrees of flexion . Both the experimental and control groups received up to 10 minutes of shoulder exercises and st and ard upper-limb care . MAIN OUTCOME MEASURES Contracture was measured as the maximum passive shoulder external rotation and flexion of the affected side as compared with the intact side . Measures were taken at 2 and 6 weeks after stroke by an assessor blinded to group allocation . RESULTS The 30-minute program of positioning the shoulder in maximum external rotation significantly reduced the development of contractures in the experimental group , compared with the control group ( P = .03 ) . The 30-minute program of positioning the shoulder in 90 degrees of flexion did not prevent contractures in the experimental group as compared with the control group ( P = .88 ) . CONCLUSIONS At least 30 minutes a day of positioning the affected shoulder in external rotation should be started as soon as possible for stroke patients who have little activity in the upper arm Painful stiffening of the shoulder , ‘ frozen shoulder ’ is a common cause of shoulder pain and disability . Continuous passive motion ( CPM ) is an established method of preventing joint stiffness and of overcoming it . A r and omized , comparative prospect i ve clinical trial was planned to compare the early response with different rehabilitation methods [ CPM vs. conventional physiotherapy treatment ( CPT ) protocol ] for adhesive capsulitis taking into consideration the clinical efficacy . A total of 57 patients with frozen shoulder were included in this study . Patients were assigned r and omly to receive daily CPM treatments or CPT protocol . Parameters were measured at baseline , and at weeks 4 and 12 . All patients were evaluated with respect to pain ( visual anologue scale ) at rest , pain at movement , pain at night , measurement of range of motion ( shoulder flexion , abduction , internal – external rotation were assessed ) , constant functional shoulder score and the shoulder pain and disability index . The first group ( n=29 ) ( CPM group ) received CPM treatments for 1 h once a day for 20 days during a period of 4 weeks . The second group ( n=28 ) ( CPT group ) had a daily physiotherapy treatment protocol including active stretching and pendulum exercises for 1 h once a day for 20 days during a period of 4 weeks . All patients in both groups were also instructed in a st and ardized home exercise programme consisting of passive range of motion and pendulum exercises to be performed every day . In both groups , statistically significant improvements were detected in all outcome measures compared with baseline . Pain reduction , however , evaluated with respect to pain at rest , at movement and at night was better in CPM group . In addition the CPM group showed better shoulder pain index scores than the CPT group . CPM treatment provides better response in pain reduction than the conventional physiotherapy treatment protocol in the early phase of treatment in adhesive capsulitis . Die schmerzhafte Schultersteife ist eine gängige Ursache für Schulterschmerzen und Behinderungen . Die kontinuierliche passive Bewegungsbeh and lung ( CPM ) ist eine gut eingeführte Method e der Verhinderung und Therapie von Gelenksteife . Mit einer r and omisierten klinischen Vergleichs- und Prospektivstudie sollte das frühe Ansprechen bei Periarthropathia humeroscapularis unter Berücksichtigung der klinischen Wirksamkeit mit verschiedenen and eren Rehabilitations method en verglichen werden [ CPM i m Vergleich mit der konventionellen Krankengymnastik ( CPT-Protokoll ) ] . An dieser Studie nahmen insgesamt 57 Patienten mit schmerzhafter Schultersteife teil . Die Patienten wurden r and omisiert der täglichen CPM-Beh and lungs- oder CPT-Protokollgruppe zugeordnet . Die Parameter wurden in der 4 . und 12 . Woche gegenüber Baseline gemessen . Alle Patienten wurden anh and ihrer Schmerzen in Ruhestellung ( visuelle Analogskala ) , bei Bewegung und in der Nacht sowie anh and der Messung des Bewegungsspielraums ( Beurteilung von Schulterflexion , -abduktion , interne – externe Rotation ) , des konstanten funktionalen Schulter-Scores , der Schulterschmerzen und des Behinderungsindexes ausgewertet . Die erste Gruppe ( n=29 ) ( CPM-Gruppe ) erhielt 20 Tage lang über einen Zeitraum von vier Wochen hinweg einmal täglich eine Stunde lang CPM-Beh and lungen . Die zweite Gruppe ( n=28 ) ( CPT-Gruppe ) wurde 20 Tage lang über einen Zeitraum von vier Wochen hinweg einmal täglich eine Stunde lang physiotherapeutisch beh and elt , u.a . mit aktiven Dehn- und Pendelübungen . Die Patienten in beiden Gruppen wurden darüber hinaus angehalten , zu Hause täglich ein St and ard-Übungsprogramm mit passiven Pendel- und Kreiselbewegungen zu befolgen . In beiden Gruppen wurden bei allen ergebnisorientierten Messgrößen statistisch signifikante Verbesserungen gegenüber Baseline festgestellt . Das Ausmaß der Schmerzlinderung war jedoch hinsichtlich der Schmerzen in Ruhestellung , bei Bewegung und in der Nacht in der CPM-Gruppe besser . Außerdem wies die CPM-Gruppe bessere Schulterschmerzen-Indexscores als die CPT-Gruppe auf . Die Schmerzlinderung bei der CPM-Beh and lung war in der frühen Beh and lungsphase bei Schultersteife besser als bei der konventionellen Krankengymnastik ( CPT-Protokoll ) . La rigidez dolorosa del hombro , conocida como ‘ hombro congelado ’ , es una causa frecuente de dolor en el hombro y de discapacidad . La movilización pasiva continua ( MPC ) es una técnica de probada eficacia para evitar y aliviar la rigidez articular . Se diseñó un estudio comparativo prospect ivo aleatorio con el objetivo de comparar la respuesta inicial a la aplicación de diferentes técnicas de rehabilitación [ comparación entre la MPC y el protocol o de tratamiento fisioterapéutico convencional ( TFC ) ] en casos con capsulitis adhesiva , desde el punto vista de la eficacia clínica . En este estudio se incluyó un total de 57 pacientes con hombro congelado . Los pacientes fueron distribuidos al azar para recibir tratamiento con MPC o con TFC diariamente . Los parámetros estudiados se midieron al inicio del estudio , y en las semanas 4 y 12 . En todos los pacientes se evaluó el dolor ( escala análoga visual ) en reposo , el dolor con los movimientos , el dolor por las noches , el arco de movilidad ( se exploraron la flexión , la abducción , y la rotación interna y externa del hombro ) , el puntaje de funcionalidad constante del hombro y el índice de dolor en el hombro y de discapacidad . El primer grupo ( n=29 ) ( grupo MPC ) recibió tratamiento con MPC durante 1 h una vez al día durante 20 días , por un período de 4 semanas . El segundo grupo ( n=28 ) ( grupo TFC ) recibió tratamiento fisioterapéutico diario , según el protocol o establecido , que incluyó estiramiento activo y ejercicios de péndulo durante 1 h una vez al día durante 20 días , por un período de 4 semanas . A todos los pacientes de ambos grupos se indicó , además , un programa est and arizado de ejercicios en el hogar que constaban de movilización pasiva en todo el arco de movilidad y ejercicios de péndulo , que debían realizar todos los días . En ambos grupos se obtuvieron mejoras estadísticamente significativas en todas las medidas de los result ados , en comparación con los valores hallados al inicio del estudio . Sin embargo , el alivio del dolor , evaluado con relación al dolor en estado de reposo , con los movimientos y durante la noche , fue mayor en el grupo MPC . Además , en el grupo MPC se obtuvieron mejores puntajes para el índice de dolor en el hombro en comparación con el grupo TFC . Con el tratamiento con MPC se obtienen mejores result ados con cuanto al alivio del dolor que con el protocol o de tratamiento fisioterapéutico convencional en la fase inicial del tratamiento en los pacientes con capsulitis adhesiva . Le raidissement douloureux de l'épaule , la sensation d'avoir « l'épaule bloquée » est une cause fréquente de douleur à l'épaule et de h and icap . Le mouvement passif continu ( continuous passive motion – CPM ) est une méthode qui permet de prévenir la rigidité et de la surmonter . Un essai clinique r and omisé comparatif prospect if a été envisagé pour comparer la réponse initiale avec différentes méthodes de rééducation ( CPM ou protocol e conventionnel de traitement de physiothérapie - CPT ) de la capsulite adhésive , en tenant compte de l'efficacité clinique . Un total de 57 patients souffrant de symptômes d'épaule bloquée ont été inclus dans cette étude . Les patients ont été affectés aléatoirement à des traitements CPM quotidiens ou au protocol e CPT . Les paramètres ont été mesurés au départ , puis aux semaines 4 et 12 . Tous les patients ont été évalués en termes de douleur ( échelle visuelle analogue ) au repos , de douleur en situation de mouvement , de douleur pendant la nuit , de mesure d'amplitude de mouvement ( la flexion de l'épaule , l'abduction , la rotation interne-externe ont été évaluées ) , de score fonctionnel constant de l'épaule , douleur à l'épaule et indice d'invalidité . Le premier groupe ( n=29 ) ( groupe CPM ) a reçu des traitements CPM de 1 h une fois par jour pendant 20 jours au cours d'une période de 4 semaines . Le deuxième groupe ( n=28 ) ( groupe CPT ) a reçu quotidiennement des traitements par protocol e actif de physiothérapie , notamment des exercices d'étirements et de suspension pendant 1 h une fois par jour pendant 20 jours au cours d'une période de 4 semaines . Les patients des deux groupes ont également reçu une formation st and ard à un programme d'exercices à domicile composé d'une série d'exercices passifs de mouvement et de suspension à effectuer chaque jour . Chez les deux groupes , des améliorations statistiquement significatives ont été notées dans tous les résultats par rapport aux mesures de base . Toutefois , la réduction de douleur , évaluée en termes de douleur au repos , en mouvement et pendant la nuit , s'est avérée plus marquée chez le groupe CPM . En outre , le groupe CPM a affiché de meilleurs scores que le groupe CPT sur l'indice de douleur à l'épaule . Le traitement CPM permet d'obtenir une meilleure réponse en termes de réduction de la douleur que le protocol e conventionnel de traitement de physiothérapie dans la première phase de traitement de la capsulite adhésive Background Physiotherapy treatment of frozen shoulder is varied , but most lack specific focus on the underlying disorder , which is the adhered shoulder capsule . Although positive effects were found after physiotherapy , the recurrence and prolonged disability of a frozen shoulder are major factors to focus on to provide the appropriate treatment . Questions / purpose sWe wished to study the effectiveness of a shoulder countertraction apparatus on ROM , pain , and function in patients with a frozen shoulder and compare their results with those of control subjects who received conventional physiotherapy . Methods A total of 100 participants were r and omly assigned to an experimental group and a control group , with each group having 50 participants . The control group received physiotherapy and the experimental group received countertraction and physiotherapy . The total treatment time was 20 minutes a day for 5 days per week for 2 weeks . The outcome measures used were goniometer measurements , VAS , and the Oxford Shoulder Score . Results Improvements were seen in the scores for shoulder flexion ( 94.1 ° ± 19.79 ° at baseline increased to 161.9 ° ± 13.05 ° after intervention ) , abduction ROM ( 90.4 ° ± 21.18 ° at baseline increased to 154.8 ° ± 13.21 ° after intervention ) , and pain ( 8.00 ± 0.78 at baseline decreased to 3.48 ± 0.71 after intervention ) in the experimental group . Sixty percent of the participants ( n = 30 ) were improved to the fourth stage of satisfactory joint function according to the Oxford Shoulder Score in the experimental group compared with 18 % ( n = 9 ) in the control group ( p < 0.001 ) . Conclusions Incorporating shoulder countertraction along with physiotherapy improves shoulder function compared with physiotherapy alone for the treatment of a frozen shoulder . Additional studies are needed focusing on this concept to increase the generalizability of the counter-traction apparatus in various groups . Level of Evidence Level II , prospect i ve comparative study . See the Instructions for Authors for a complete description of levels of evidence STUDY DESIGN R and omized clinical trial . OBJECTIVE To compare the effectiveness of anterior versus posterior glide mobilization techniques for improving shoulder external rotation range of motion ( ROM ) in patients with adhesive capsulitis . BACKGROUND Physical therapists use joint mobilization techniques to treat motion impairments in patients with adhesive capsulitis . However , opinions of the value of anterior versus posterior mobilization procedures to improve external rotation ROM differ . METHODS AND MEASURES Twenty consecutive subjects with a primary diagnosis of shoulder adhesive capsulitis and exhibiting a specific external rotation ROM deficit were r and omly assigned to 1 of 2 treatment groups . All subjects received 6 therapy sessions consisting of application of therapeutic ultrasound , joint mobilization , and upper-body ergometer exercise . Treatment differed between groups in the direction of the mobilization technique performed . Shoulder external rotation ROM measured initially and after each treatment session was compared within and between groups and analyzed using a 2-way ANOVA , followed by paired and independent t tests . RESULTS There was no significant difference in shoulder external rotation ROM between groups prior to initiating the treatment program . A significant difference between groups ( P = .001 ) was present by the third treatment . The individuals in the anterior mobilization group had a mean improvement in external rotation ROM of 3.0 degrees ( SD , 10.8 degrees ; P = .40 ) , whereas the individuals in the posterior mobilization group had a mean improvement of 31.3 degrees ( SD , 7.4 degrees ; P < .001 ) . CONCLUSIONS A posteriorly directed joint mobilization technique was more effective than an anteriorly directed mobilization technique for improving external rotation ROM in subjects with adhesive capsulitis . Both groups had a significant decrease in pain |
581 | 28,570,713 | Conclusions Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection . | Objective The present study aim ed to undertake a review of available evidence assessing whether time-lapse imaging ( TLI ) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization ( IVF ) . | OBJECTIVE To determine if the addition of continuous morphokinetic data improves reproductive outcomes when all embryos are cultured in a closed system . DESIGN Prospect i ve , r and omized , controlled study . SETTING Single academic center . PATIENT(S ) A total of 235 patients undergoing fresh autologous IVF cycles with at least four embryos , cultured in the Embryoscope : 116 patients r and omized to conventional once-daily morphologic embryo screening ( CS ) and 119 to additional time-lapse kinetic monitoring ( TLM ) for selection . INTERVENTION(S ) TLM versus CS . MAIN OUTCOME MEASURE(S ) Intrauterine clinical pregnancy ( CPR ) and implantation ( IR ) rates . RESULT ( S ) CPR and IR were similar overall ( TLM vs. CS , respectively : CPR 68 % vs. 63 % ; IR 51 % vs. 45 % ) and with blastocyst transfers ( CPR 74 % vs. 67 % ; IR 56 % vs. 51 % ) . CPR with day 5 transfer was threefold higher than day 3 transfer , but group ( TLM vs. CS ) was not a significant predictor of clinical pregnancy or implantation . Significantly more multinucleation was detected when CS embryos were retrospectively review ed with the use of TLM ( 7.0 % vs. 35.3 % ) , and multinucleation was independently associated with decreased rates of implantation . Time to the start of blastulation of < 100 hours after insemination and the morphokinetic scoring system used in the TLM group were independently associated with implantation . CONCLUSION ( S ) The addition of time-lapse morphokinetic data did not significantly improve clinical reproductive outcomes in all patients and in those with blastocyst transfers . Absence of multinucleation , timing of blastulation , and morphokinetic score were found to be associated with blastocyst implantation rates . CLINICAL TRIAL REGISTRATION NUMBER NCT02081859 Background Previously manual human embryology in many in vitro fertilization ( IVF ) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging . Whether such systems perform comparably to manual embryology in different IVF patient population s has , however , never before been investigated . We , therefore , prospect ively compared embryo quality following closed system culture with time-lapse photography ( EmbryoScope ™ ) and st and ard embryology . We performed a two-part prospect ively r and omized study in IVF ( clinical trial # NCT92256309 ) . Part A involved 31 infertile poor prognosis patients prospect ively r and omized to EmbryoScope ™ and st and ard embryology . Part B involved embryos from 17 egg donor-recipient cycles result ing in large egg/embryo numbers , thus permitting prospect ively alternative embryo assignments to EmbryoScope ™ and st and ard embryology . We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo . Results Part A revealed in poor prognosis patients no differences in day-3 embryo scores , implantation and clinical pregnancy rates between EmbryoScope ™ and st and ard embryology . The EmbryoScope ™ , however , more than doubled embryology staff time ( P < 0.0001 ) . In Part B , embryos grown in the EmbyoScope ™ demonstrated significantly poorer day-3 quality ( depending on embryo parameter between P = 0.005 and P = 0.01 ) . Suspicion that conical culture dishes of the EmbryoScope ™ ( EmbryoSlide ™ ) may be the cause was disproven when st and ard culture dishes demonstrated no outcome difference in st and ard incubation . Conclusions Though due to small patient numbers preliminary , this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology . Appropriately design ed and powered prospect ively r and omized studies appear urgently needed in well-defined patient population s before the uncontrolled utilization of these instruments further exp and s . Trial registration NCT02246309 Registered September 18 , 2014 OBJECTIVE To quantify the effect on reproductive outcome of culturing and selecting embryos using a novel time-lapse monitoring system ( TMS ) . DESIGN Retrospective observational cohort study . SETTING University-affiliated private center . PATIENT(S ) Donation and autologous intracytoplasmic sperm injection ( ICSI ) cycles from ten IVF clinics using similar procedures , cultured in TMS ( n = 1,390 ) or in a st and ard incubator ( SI ; n = 5,915 ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rate confirmed by ultrasound in week 7 . RESULT ( S ) A logistic regression analysis , which included all significant confounding factors , was used to evaluate the effect of culturing and selecting embryos with the use of TMS . Comparing clinical pregnancy rates per oocyte retrieval with TMS and SI treatments gave a crude effect of odds ratio [ OR ] 1.190 ( 95 % confidence interval [ CI ] 1.058 - 1.337 ) . Oocyte source , maternal age , day of transfer , and number of retrieved oocytes were identified as significant confounding factors . After accounting for confounding factors , the effect of TMS culture was OR 1.201 ( 95 % CI 1.059 - 1.363 ) . Limiting analysis to treatments with embryo transfer and including number of transferred embryos as a confounding factor likewise gave a significant effect of TMS with OR 1.157 ( 95 % CI 1.018 - 1.315 ) . CONCLUSION ( S ) Analysis of retrospective data indicated that culturing and selecting embryos by TMS significantly improved the relative probability of clinical pregnancy ( + 20.1 % per oocyte retrieval , + 15.7 % per embryo transfer ) . The elevated clinical pregnancy rate was attributed to a combination of stable culture conditions and the use of morphokinetic parameters for embryo selection OBJECTIVE To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system ( TMS ) and selection supported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in a st and ard incubator ( SI ) embryo culture and selection based exclusively on morphology . DESIGN Prospect i ve , r and omized , double-blinded , controlled study . SETTING University-affiliated private in vitro fertilization ( IVF ) clinic . PATIENT(S ) Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection ( ICSI ) . INTERVENTION(S ) No patient intervention ; embryos cultured in SI with development evaluated only by morphology ( control group ) and embryos cultured in TMS with embryo selection was based on a multivariable model ( study group ) . MAIN OUTCOME MEASURE(S ) Rates of embryo implantation , pregnancy , ongoing pregnancy ( OPR ) , and early pregnancy loss . RESULT ( S ) Analyzing per treated cycle , the ongoing pregnancy rate was statistically significantly increased 51.4 % ( 95 % CI , 46.7 - 56.0 ) for the TMS group compared with 41.7 % ( 95 % CI , 36.9 - 46.5 ) for the SI group . For pregnancy rate , differences were not statistically significant at 61.6 % ( 95 % CI , 56.9 - 66.0 ) versus 56.3 % ( 95 % CI , 51.4 - 61.0 ) . The results per transfer were similar : statistically significant differences in ongoing pregnancy rate of 54.5 % ( 95 % CI , 49.6 - 59.2 ) versus 45.3 % ( 95 % CI , 40.3 - 50.4 ) and not statistically significant for pregnancy rate at 65.2 % ( 95 % CI , 60.6 - 69.8 ) versus 61.1 % ( 95 % CI , 56.2 - 66.1 ) . Early pregnancy loss was statistically significantly decreased for the TMS group with 16.6 % ( 95 % CI , 12.6 - 21.4 ) versus 25.8 % ( 95 % CI , 20.6 - 31.9 ) . The implantation rate was statistically significantly increased at 44.9 % ( 95 % CI , 41.4 - 48.4 ) versus 37.1 % ( 95 % CI , 33.6 - 40.7 ) . CONCLUSION ( S ) The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improves reproductive outcomes . CLINICAL TRIAL REGISTRATION NUMBER NCT01549262 Purpose To assess the effects of light from an integrated optical microscope and evaluate the safety of time-lapse observations using a built-in microscope incubator . Methods We prospect ively compared the fertilization rate and embryonic morphology after intracytoplasmic sperm injection between embryos cultured with time-lapse observations every 15 min in an incubator with an integrated optical microscope and embryos with intermittent observations ( once a day ) in conventional incubators . Results No significant differences were observed in the fertilization rate ( 57.5 % vs. 57.5 % ) or the rate of excellent-good cleavage embryos ( 36.0 % vs. 36.0 % ) . Conclusions These results suggest that time-lapse observations using an incubator with an integrated optical microscope may therefore be safely utilized in clinical practice STUDY QUESTION Does culture in a closed system result in an increased number of good quality embryos ( GQE ) on Day 2 compared with culture in a conventional system ? SUMMARY ANSWER Culture in a closed system up to 2 days after microinjection results in similar embryo development and morphological quality compared with culture in a conventional incubation system . WHAT IS KNOWN ALREADY Time-lapse imaging ( TLI ) incubators are rapidly being introduced into IVF laboratories worldwide , despite the lack of large prospect i ve r and omized trials demonstrating improvement in embryo development or pregnancy rates . STUDY DESIGN , SIZE , DURATION A r and omized controlled trial including 364 patients ( 365 cycles ) was conducted between May 2010 and February 2014 . After oocyte collection , r and omization was carried out and all of a patients ' oocytes were allocated to culture in either a conventional incubator or a closed incubator system in proportion 1:2 until embryo transfer on Day 2 . A total of 1979 oocytes were injected and cultured in the closed system , and 1000 in the st and ard incubator . The primary end-point was the number of GQE in the two groups . PARTICIPANTS / MATERIAL S , SETTING S , METHODS In total , 364 patients undergoing their first IVF cycle using ICSI , where at least one oocyte was retrieved , were r and omized in a university hospital setting . Two hundred and forty patients were r and omized for culture in a closed system and 124 patients for culture in the conventional incubator system ( control group ) . Embryo assessment s and final morphological scoring before transfer and cryopreservation were carried out at the same time points for embryos cultured in the conventional incubator and in the closed system . MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in the mean ± SD number of GQEs between groups : 2.41 ± 2.27 for the closed system group and 2.19 ± 1.82 for the control group ( P = 0.34 , difference 0.23 , 95 % confidence interval 0.69 ; -0.24 ) . No significant differences were found in the number of 4-cell embryos , implantation- , pregnancy- or ongoing pregnancy rates . A significantly higher miscarriage rate was found in the TLI group compared with the control group ( 33.3 and 10.2 % , P = 0.01 ) . LIMITATIONS , REASONS FOR CAUTION Culture media , temperature and gas levels were similar in the open and closed incubator systems , but different culture dishes were used . Culturing embryos for longer time period ( to the blastocyst stage ) may give different results . Only ICSI patients were included , which may limit the generalizability of the results . Finally , the number of GQEs on Day 2 was used as a surrogate outcome for live birth . WIDER IMPLICATION S OF THE FINDINGS The results are consistent with other , smaller r and omized trials showing no difference in embryo quality when comparing culture in a conventional incubator with that of a closed TLI incubator system BACKGROUND Time-lapse observation presents an opportunity for optimizing embryo selection based on morphological grading as well as providing novel kinetic parameters , which may further improve accurate selection of viable embryos . The objective of this retrospective study was to identify the morphokinetic parameters specific to embryos that were capable of implanting . In order to compare a large number of embryos , with minimal variation in culture conditions , we have used an automatic embryo monitoring system . METHODS Using a tri-gas IVF incubator with a built-in camera design ed to automatically acquire images at defined time points , we have simultaneously monitored up to 72 individual embryos without removing the embryos from the controlled environment . Images were acquired every 15 min in five different focal planes for at least 64 h for each embryo . We have monitored the development of transferred embryos from 285 couples undergoing their first ICSI cycle . The total number of transferred embryos was 522 , of which 247 either failed to implant or fully implanted , with full implantation meaning that all transferred embryos in a treatment implanted . RESULTS A detailed retrospective analysis of cleavage times , blastomere size and multinucleation was made for the 247 transferred embryos with either failed or full implantation . We found that several parameters were significantly correlated with subsequent implantation ( e.g. time of first and subsequent cleavages as well as the time between cleavages ) . The most predictive parameters were : ( i ) time of division to 5 cells , t5 ( 48.8 - 56.6 h after ICSI ) ; ( ii ) time between division to 3 cells and subsequent division to 4 cells , s2 ( ≤ 0.76 h ) and ( iii ) duration of cell cycle two , i.e. time between division to 2 cells and division to 3 cells , cc2 ( ≤ 11.9 h ) . We also observed aberrant behavior such as multinucleation at the 4 cell stage , uneven blastomere size at the 2 cell stage and abrupt cell division to three or more cells , which appeared to largely preclude implantation . CONCLUSIONS The image acquisition and time-lapse analysis system makes it possible to determine exact timing of embryo cleavages in a clinical setting . We propose a multivariable model based on our findings to classify embryos according to their probability of implantation . The efficacy of this classification will be evaluated in a prospect i ve r and omized study that ultimately will determine if implantation rates can be improved by time-lapse analysis STUDY QUESTION To what extent do patient- and treatment-related factors explain the variation in morphokinetic parameters proposed as embryo viability markers ? SUMMARY ANSWER Up to 31 % of the observed variation in timing of embryo development can be explained by embryo origin , but no single factor elicits a systematic influence . WHAT IS KNOWN ALREADY Several studies report that culture conditions , patient characteristics and treatment influence timing of embryo development , which have promoted the perception that each clinic must develop individual models . Most of the studies have , however , treated embryos from one patient as independent observations , and only very few studies that evaluate the influence from patient- and treatment-related factors on timing of development or time-lapse parameters as predictors of viability have controlled for confounding , which implies a high risk of overestimating the statistical significance of potential correlations . STUDY DESIGN , SIZE , DURATION Infertile patients were prospect ively recruited to a cohort study at a hospital fertility clinic from February 2011 to May 2013 . Patients aged < 38 years without endometriosis were eligible if ≥8 oocytes were retrieved . Patients were included only once . All embryos were monitored for 6 days in a time-lapse incubator . PARTICIPANTS / MATERIAL S , SETTING , METHODS A total of 1507 embryos from 243 patients were included . The influence of fertilization method , BMI , maternal age , FSH dose and number of previous cycles on timing of t2-t5 , duration of the 2- and 3-cell stage , and development of a blastocoel ( tEB ) and full blastocoel ( tFB ) was tested in multivariate , multilevel linear regression analysis . Predictive parameters for live birth were tested in a logistic regression analysis for 223 single transferred blastocysts , where time-lapse parameters were investigated along with patient and embryo characteristics . MAIN RESULTS AND THE ROLE OF CHANCE Moderate intra-class correlation coefficients ( 0.16–0.31 ) were observed for all parameters except duration of the 3-cell stage , which demonstrates that embryos from one patient elicit clustering at a patient level . No single patient- and treatment-related factor was found to systematic ally influence the timing from cleavage to blastocyst stage , which indicates that no individual patient-related factor can be identified that separately explains the clustering throughout the entire developmental stages . The blastocyst parameters were more affected by patient-related factors than cleavage stage parameters , as tEB occurred significantly later with older age ( 0.29 h/year ( 95 % confidence interval : CI 0.03 ; 0.56 ) ) , while both tEB and tFB occurred significantly later with increasing dose of FSH ( tEB : 0.12 h/100 IU FSH ( 95 % CI 0.01;0.24 ) ; tFB 0.14 h/100 IU FSH ( 95 % CI 0.03;0.27 ) ) and with more previous attempts ( tEB : 1.2 h/attempt ( 95 % CI 0.01;2.5 ) ; tFB 1.4 h/attempt ( 0.10;2.7 ) ) . Fertilization method affected timing of the first division , with ICSI embryos cleaving significantly faster than IVF embryos ( −3.6 % ( 95 % CI −6.4 ; −0.77 ) ) , whereas no difference was found in the subsequent divisions . The univariable regression analysis identified female age , cumulative FSH dose , degree of blastocyst expansion , score of the inner cell mass and timing of full blastocyst formation as predictors of live birth . The timing of full blastocyst formation ( tFB ) did not remain significant when adjusting for age , number of previous cycles and cumulative FSH dose , which were the parameters shown to influence tFB in the mixed regression model . LIMITATIONS , REASONS FOR CAUTION Only good prognosis patients were enrolled , so these results may not be generalized to all infertile women . Not all patient-related factors were investigated . WIDER IMPLICATION S OF THE FINDINGS Our findings underline the importance of treating embryos as dependent observations and suggest a high risk of patient-based confounding in retrospective studies . The impact of confounders and the embryo origin needs to be addressed in order to apply appropriate statistical models in observational studies . Furthermore , this observation emphasizes the need for RCTs for evaluating use of time-lapse parameters for embryo selection . STUDY FUNDING /COMPETING INTERESTS Funding for the cohort study was provided by the Lippert Foundation , the Toyota Foundation , the Aase og Einar Danielsen foundation and NordicInfu Care research grant . Research at the Fertility Clinic , Aarhus University Hospital is supported by an unrestricted grant from MSD and Ferring . K.K. is funded by a grant from the Danish Council for Independent Research Medical Sciences . The authors declare no competing interest OBJECTIVE To determine if an automated time-lapse test ( TL-test ) combined with traditional morphology for embryo selection and day 3 transfer results in improved clinical outcomes . DESIGN Prospect i ve concurrent-controlled pilot study . SETTING IVF clinic and laboratory . PATIENT(S ) A total of 319 female patients < 41 years old , with day 3 embryo transfer , fewer than three failed IVF cycles , and at least four zygotes ( 2-pronuclear ) on day 1 . INTERVENTION(S ) Automated time-lapse embryo assessment combined with morphologic assessment in the study ( test ) group compared with morphologic assessment only ( control group ) . MAIN OUTCOME MEASURE(S ) Embryo implantation , pregnancy , and multiple pregnancy rates . Sub analysis of implantation potential of embryos based on the TL-test ( TL-high vs. TL-low ) scores . RESULT ( S ) Implantation and clinical pregnancy rates were significantly higher in the test group compared with the control group ( implantation rates 30.2 % vs. 19.0 % , clinical pregnancy rates 46.0 % vs. 32.1 % , respectively ) . Multiple pregnancy rates were not statistically different ( 26.7 % vs. 18.3 % ) . Test group patients receiving at least one TL-high embryo had significantly higher implantation rates than patients receiving only TL-low embryos ( 36.8 % vs. 20.6 % ) . TL-high compared with TL-low embryos had significantly higher implantation rates ( 44.7 % vs. 20.5 % ) . Among morphologically good embryos , TL-high embryos were more likely to implant than TL-low embryos ( 44.1 % vs. 20.6 % ) . CONCLUSION ( S ) This is the first report demonstrating improved implantation rates in patients receiving day 3 embryo transfers based on the combined use of a TL-test along and traditional morphology . Our findings confirm that the noninvasive TL-test adds valuable information to traditional morphologic grading . CLINICAL TRIAL REGISTRATION NUMBER NCT01671657 STUDY QUESTION Do early time-lapse parameters predict which embryos will develop to high- quality blastocysts and does timing of development differ between embryos that implant and those that do not . SUMMARY ANSWER Development to high- quality blastocysts could be predicted within the first 48 h of culture , whereas time-lapse parameters could not predict pregnancy . WHAT IS KNOWN ALREADY Historical cohort studies on embryos from unselected groups of patients have suggested several putative kinetic markers of viability . Before well- design ed r and omized studies can be conducted , relevant selection models based on solid data must be developed . So far conclusions from the previous studies are ambiguous . STUDY DESIGN , SIZE , DURATION A prospect i ve cohort study conducted from February 2011 to June 2012 . A total of 571 ICSI embryos from 92 patients were included in the blastocyst development analysis and 84 single embryo transfers were included in the pregnancy outcome analysis . PARTICIPANTS / MATERIAL S , SETTING , METHODS Embryos from women aged < 38 years , with no endometriosis and ≥ 8 oocytes retrieved . University affiliated clinic . Embryos were cultured in a time-lapse incubator till Day 6 . Logistic regression analysis was performed with variables selected based on indication . MAIN RESULTS AND THE ROLE OF CHANCE Duration of the first cytokinesis , duration of the 3-cell stage and direct cleavage to 3-cells predicted development to high- quality blastocyst . We found no difference in timing between implanted and non-implanted embryos . LIMITATIONS , REASONS FOR CAUTION A larger study might detect differences in timing between implanted and non-implanted embryos . The cohort consisted of good prognosis patients only and may not be representative of the entire IVF population . WIDER IMPLICATION S OF THE FINDINGS Our results in context with the lack of consistency in previous studies and the presumed influences of different external factors indicate that a universal algorithm for optimal timing of development might not be feasible . The apparent negative significance of division patterns that differ from the expected may imply that time-lapse will facilitate de- selection of embryos . STUDY FUNDING /COMPETING INTEREST(S ) Funding for the present study was provided by Aarhus University , the Lippert Foundation , the Toyota Foundation , the Aase og Einar Danielsen foundation and by an unrestricted grant from MSD and Ferring . The authors declare no conflict of interest . TRIAL REGISTRATION NUMBER The study was registered at Clinical Trial.gov with accession number NCT01139268 OBJECTIVE To present a time-lapse de selection model involving both qualitative and quantitative parameters for assessing embryos on day 3 . DESIGN Retrospective cohort study and prospect i ve validation . SETTING Private IVF center . PATIENT(S ) A total of 270 embryos with known implantation data ( KID ) after day 3 transfer from 212 IVF/intracytoplasmic sperm injection ( ICSI ) cycles were retrospectively analyzed for building the proposed de selection model , followed by prospect i ve validation using an additional 66 KID embryos . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Morphological score on day 3 , embryo morphokinetic parameters , abnormal cleavage patterns , and known implantation results . RESULT ( S ) All included embryos were categorized either retrospectively or prospect ively into 7 grade s ( A+ , A , B , C , D , E , F ) . Qualitative de selection parameters included poor conventional day 3 morphology , abnormal cleavage patterns identified via time-lapse monitoring , and < 8 cells at 68 hours postinsemination . Quantitative parameters included time from pronuclear fading ( PNF ) to 5-cell stage and duration of 3-cell stage . KID implantation rates of embryos grade d from A+ to F were 52.9 % , 36.1 % , 25.0 % , 13.8 % , 15.6 % , 3.1 % , and 0 respectively ( area under the curve [ AUC ] = 0.762 ; 95 % confidence interval [ CI ] , 0.701 - 0.824 ) , and a similar pattern was seen in either IVF ( AUC = 0.721 ; 95 % CI , 0.622 - 0.821 ) or ICSI embryos ( AUC = 0.790 ; 95 % CI , 0.711 - 0.868 ) . Preliminary prospect i ve validation using 66 KID embryos also showed statistically significant prediction in Medicult ( AUC = 0.750 ; 95 % CI , 0.588 - 0.912 ) and Vitrolife G-Series ( AUC = 0.820 ; 95 % CI , 0.671 - 0.969 ) suites of culture media . CONCLUSION ( S ) The proposed model involving both qualitative and quantitative de selection effectively predicts day 3 embryo implantation potential and is applicable to all IVF embryos regardless of insemination method by using PNF as the reference starting time point Purpose In the current study , our aim was to demonstrate that EmbryoScope incubation conditions is comparable to st and ard laboratory incubation circumstances by comparing embryo quality , development and ongoing pregnancy rates between the EmbryoScope ( ES ) and a st and ard incubator ( SI ) . We analyzed 478 embryos from 60 couples undergoing oocyte donation were included in the study . Methods All embryos retrieved from a patient were r and omly distributed in the ES or SI . We calculated blastocyst development rate , blastocyst viability and ongoing pregnancy rate for embryo transfers from ES , SI and mixed ( one embryo from the ES and one from the SI ) . Statistical analysis was conducted by Chi square tests , considering p < 0.05 significant . Results No significant differences were found between the ES and SI from all the parameters evaluated . Conclusions Thus we concluded that time-lapse monitoring in the EmbryoScope does not impair embryo quality while allowing for morphological , spatial and temporal analysis of embryo development Objective To compare the dynamics of early development between embryos cultured in single and sequential media . Design R and omized , comparative study . Setting Private IVF centre . Patients A total of 446 metaphase II oocytes from 51 couples who underwent oocyte retrieval procedure for intracytoplasmic sperm injection . Forty-nine result ed in embryo transfer . InterventionOocytes were split between single and sequential media produced by the same manufacturer and cultured in a time-lapse incubator . Main outcome measures Morphokinetic parameters until the embryos reached the 5-cell stage ( t5 ) , utilization , clinical pregnancy and implantation rates . Results Embryos cultured in single media were advanced from the first mitosis cycle and reached 2- to 5-cell stages earlier . There was not any difference between the duration s for cell cycle two ( cc2 = t3-t2 ) and s2 ( t4-t3 ) . The utilization , clinical pregnancy and implantation rates did not differ between groups . The proportion of cryopreserved day6 embryos to two pronuclei oocytes was significantly higher in sequential than in single media . Conclusions Morphokinetics of embryo development vary between single and sequential culture media at least until the 5-cell stage . The overall clinical and embryological parameters remain similar regardless of the culture system Purpose Time-lapse monitoring allows for a flexible embryo evaluation and potentially provides new dynamic markers of embryo competence . Before introducing time-lapse monitoring in a clinical setting , the safety of the instrument must be properly documented . Accordingly , the aim of this study was to evaluate the safety of a commercially available time-lapse incubator . Methods In a two center , r and omized , controlled , clinical trial 676 oocytes from 59 patients in their 2nd or third treatment cycle , age < 38 years and ≥8 oocytes retrieved were cultured in the time-lapse incubator or in a conventional incubator . The primary outcome was proportion of 4-cell embryos on day 2 . Secondary outcomes were proportion of 7–8 cell embryos on day 3 and proportion of blastocysts on day 5 . Implantation pregnancy rates were registered based on presence of fetal heart activity visualized by ultrasound 8 weeks after embryo transfer . Results No significant difference was found between the time-lapse incubator ( TLI ) and conventional incubator ( COI ) in proportion of 4-cell embryos on day 2 irrespective of whether data was analyzed according to ITT ( RRTLI/COI : 0.81 ( 0.65 ; 1.02 ) ) or PP ( RRTLI/COI : 0.80 ( 0.63 ; 1.01 ) ) . Nor were any significant differences detected in the secondary endpoints ; i.e. proportion of 7–8-cell embryos on day three ITT ( RRTLI/COI : 0.96 ( 0.73 ; 1.26 ) ) ; PP ( RRTLI/COI : 0.95 ( 0.72 ; 1.26 ) ) and proportion of blastocysts on day five ITT ( RRTLI/COI : 1.09 ( 0.84 ; 1.41 ) ) ; PP ( RRTLI/COI : 1.09 ( 0.83 : 1.41 ) ) . We found no differences in clinical pregnancy rate or implantation rate . Conclusion Culture in the time-lapse incubator supports embryonic development equally to a conventional incubator OBJECTIVE To evaluate , using time-lapse monitoring , the temporal influence of culture in 5 % O2 or 20 % O2 on human embryonic development . DESIGN Retrospective cohort study . SETTING University-based fertility clinic . PATIENT(S ) In vitro fertilized embryos from women aged < 38 years with no endometriosis and ≥8 oocytes retrieved . INTERVENTION(S ) Culture in 20 % O2 exclusively ( group 1 ) , 20 % and 5 % O2 combined ( group 2 ) , or 5 % O2 exclusively ( group 3 ) . MAIN OUTCOME MEASURE(S ) Developmental rates and timing of developmental stages . RESULT ( S ) The timing of the third cleavage cycle was delayed for embryos cultured in 20 % O2 ( group 1 ) compared with embryos cultured in 5 % O2 ( groups 2 and 3 ) . No difference was observed in timing of the early and full blastocyst stages . More embryos in groups 2 and 3 reached the 8-cell , early blastocyst , and full blastocyst stages than in group 1 . We found that embryos in group 3 ( 5 % O2 ) reached the 8-cell stage faster than embryos in group 2 ( 5 % + 20 % O2 ) , but none of the other parameters ( i.e. , other time points , cumulative development , and embryo score ) differed between the two groups . CONCLUSION ( S ) Culture in 20 % O2 reduces developmental rates and delays completion of the third cell cycle . The delayed development after culture in atmospheric oxygen was seen in the precompaction embryo only and therefore appears to be stage specific . CLINICAL TRIAL REGISTRATION NUMBER NCT01139268 STUDY QUESTION Are the morphokinetics of growing embryos affected by the type of culture media utilized ? SUMMARY ANSWER Morphokinetic parameters used for embryo selection are not affected between the two different concept culture media analyzed . WHAT IS KNOWN ALREADY Studies on the effect of culture media on human embryos have focused on evaluating different in-house and commercially available media as well as comparing outcomes among different commercial media . Nonetheless , the evaluation of embryo development in these studies was based on static observations and very little is known from a dynamic point of view . STUDY DESIGN , SIZE , DURATION Prospect i ve cohort study , October 2010 and April 2011 . PARTICIPANTS / MATERIAL S , SETTING , METHODS University-affiliated infertility center . Patients undergoing egg donation ( n = 75 ) in which embryos were cultured with two different types of media in a time-lapse system . Embryo development was analyzed with time-lapse imaging for single step media ( Global ® ) and sequential media ( Sage ® Cleavage ) . Variables studied included the timing to two cells ( t2 ) , three cells ( t3 ) , four cells ( t4 ) and five cells ( t5 ) as well as the length of the second cell cycle ( cc2 = t3 - t2 ) and the synchrony in the division from two to four cells ( s2 = t4 - t3 ) . Implantation and clinical pregnancy rates were also analyzed . MAIN RESULTS AND THE ROLE OF CHANCE No statistically significant differences were observed between the two media for all the variables analyzed . When analyzing the percentage of embryos falling within the optimal ranges proposed for s2 , cc2 and t5 , we did not find significant differences between the two media . Pregnancy and implantation rates were similar for the three types of transfers : 48.0 % ( CI 95 % 28.4 - 67.6 ) and 42.0 % ( CI 95 % 22.5 - 61.4 ) with Global media ; 58.8 % ( CI 95 % 35.4 - 82.2 ) and 38.2 % ( CI 95 % 15.0 - 61.4 ) with Cleavage media ; and 58.1 % ( CI 95 % 40.7 - 75.4 ) and 37.1 % ( CI 95 % 22.1 - 52.1 ) with mixed transferred , respectively . Multiple implantations ( twins ) were also similar among the three groups , with 24.0 % ( CI 95 % 9.3 - 45.1 ) for transfers with embryos cultured in Global media , 17.6 % ( CI 95 % 3.7 - 43.3 ) for transfers with embryos cultured in Cleavage media and 22.5 % ( CI 95 % 9.5 - 41.0 ) with mixed transfers . LIMITATIONS , REASONS FOR CAUTION The study was not powered to test differences in pregnancy rates between the two culture media , as this was not the hypothesis tested . Results are based on observations with embryos from oocyte donors and need to be repeated with embryos from infertile patients of different ages . WIDER IMPLICATION S OF THE FINDINGS The absence of differences in morphokinetics between two different media concepts vali date s the algorithm for embryo selection in diverse culture conditions . STUDY FUNDING /COMPETING INTEREST(S ) No specific funding was obtained for this study ; it was solely funded by IVI . None of the authors have any economic affiliation with Unisense Fertilitech A/S but IVI is a minor shareholder in Unisense Fertilitech STUDY QUESTION Does prospect i ve embryo selection using the results from the Eava Test ( Early Embryo Viability Assessment ) in combination with st and ard morphology increase the pregnancy rate of IVF and ICSI patients compared to embryo selection based on morphology only ? SUMMARY ANSWER Embryo selection using the Eeva Test plus st and ard morphology on Day 3 results in comparable pregnancy rates as conventional morphological embryo selection . WHAT IS KNOWN ALREADY Time-lapse monitoring of embryo development may represent a superior way to culture and select embryos in vitro . The Eeva Test records the development of each embryo with a cell-tracking system and predicts the likelihood ( High , Medium or Low ) that an embryo will form a blastocyst based on an automated analysis of early cell division timings . STUDY DESIGN , SIZE , DURATION This trial was design ed as a prospect i ve , observational , two-center pilot study with a propensity matched control group . The analysis involved 280 of 302 enrolled patients who were included in the Eeva Test group in 2013 and 560 control patients who were treated in the years 2011 - 2013 . The majority of transfers ( 98 % ) were single embryo transfers . PARTICIPANTS / MATERIAL S , SETTING , METHODS Two academic hospitals ( VUmc Amsterdam and UZ Gent ) enrolled patients < 41 years old , with <3 previous attempts and ≥5 normally fertilized eggs . Propensity matching was used to identify a propensity matched control group from a cohort of 1777 patients based on age , cycle number , oocyte number and number of fertilized oocytes . MAIN RESULTS AND THE ROLE OF CHANCE There was no difference in patient baseline characteristics between the two groups . The ongoing pregnancy rate ( OPR ) of patients enrolled in the Eeva Test group ( 34.3 % ; 96/280 ) did not differ significantly from the OPR in the propensity matched control group ( 34.6 % , 194/560 ; P = 0.92 ) . However , significantly less top quality embryos ( eight-cell embryos with ≤25 % fragmentation ) were transferred in the Eeva Test group compared to the propensity matched control group ( 70.4 % vs. 82.3 % ; P < 0.001 ) . The transfer of Eeva High and Medium embryos result ed in a significantly higher OPR of 36.8 % ( 89/242 ) compared to 18.4 % ( 7/38 ) for Eeva Low embryos ( P = 0.02 ) . LIMITATION , REASONS FOR CAUTION This pilot study is limited by its nonr and omized design with a concurrent and historical control . WIDER IMPLICATION S OF THE FINDINGS Our pilot data did not reveal significant differences between time-lapse based and conventional embryo selection . Interestingly , the pregnancy rates were comparable in both groups even though the morphological quality of the transferred embryos was significantly lower in the Eeva Test group compared to the propensity matched control group . A sufficiently powered three-armed r and omized controlled trial ( RCT ) with a solid design should be performed to generate decisive evidence in the future . STUDY FINDING/COMPETING INTERESTS Progyny Inc. , formerly Auxogyn provided the Eeva scopes , software and technical support for this study . The funding sources did neither influence data collection , management , analysis and interpretation of the data , nor the preparation of the manuscript . TRIAL REGISTRATION NUMBER Clinical Trials.gov : NCT01671644 OBJECTIVE To assess the first computer-automated platform for time-lapse image analysis and blastocyst prediction and to determine how the screening information may assist embryologists in day 3 ( D3 ) embryo selection . DESIGN Prospect i ve , multicenter , cohort study . SETTING Five IVF clinics in the United States . PATIENT(S ) One hundred sixty women ≥ 18 years of age undergoing fresh IVF treatment with basal antral follicle count ≥ 8 , basal FSH < 10 IU/mL , and ≥ 8 normally fertilized oocytes . INTERVENTION(S ) A noninvasive test combining time-lapse image analysis with the cell-tracking software , Eeva ( Early Embryo Viability Assessment ) , was used to measure early embryo development and generate usable blastocyst predictions by D3 . MAIN OUTCOME MEASURE(S ) Improvement in the ability of experienced embryologists to select which embryos are likely to develop to usable blastocysts using D3 morphology alone , compared with morphology plus Eeva . RESULT ( S ) Experienced embryologists using Eeva in combination with D3 morphology significantly improved their ability to identify embryos that would reach the usable blastocyst stage ( specificity for each of three embryologists using morphology vs. morphology plus Eeva : 59.7 % vs. 86.3 % , 41.9 % vs. 84.0 % , 79.5 % vs. 86.6 % ) . Adjunctive use of morphology plus Eeva improved embryo selection by enabling embryologists to better discriminate which embryos would be unlikely to develop to blastocyst and was particularly beneficial for improving selection among good-morphology embryos . Adjunctive use of morphology plus Eeva also reduced interindividual variability in embryo selection . CONCLUSION ( S ) Previous studies have shown improved implantation rates for blastocyst transfer compared with cleavage-stage transfer . Addition of Eeva to the current embryo grading process may improve the success rates of cleavage-stage ETs |
582 | 20,978,445 | The meta- analysis of topotecan regimens ( TP ) was not reliable due to impending heterogeneity .
The present meta- analysis demonstrates statistically significant OS and PFS benefits of IP over EP regimens in western and eastern patients . | INTRODUCTION Superiority of camptothecin regimens over etoposide-both combined with platinum analogs-in extensive disease small cell lung cancer has been a matter of debate with contradictory findings in r and omized trials .
A systematic review was sought to eluci date this issue . | BACKGROUND Recent dose-intensity studies of small-cell lung cancer ( SCLC ) have yielded conflicting results . We carried out a phase III r and omized trial in patients with better-prognosis SCLC ( i.e. , prognostic score of 0 - 1 ) to investigate whether doubling the dose density of ifosfamide , carboplatin , and etoposide ( ICE ) chemotherapy with filgrastim and blood-progenitor-cell support improves survival , compared with st and ard ICE chemotherapy . METHODS We studied 318 patients with pathologically proven SCLC who were r and omly assigned to receive six cycles of ICE chemotherapy with a 4-week ( st and ard arm ) or 2-week ( dose-dense arm ) interval between cycles . Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6 , which was returned 24 hours after treatment . Toxicities , including hematologic toxicity and incidence of neutropenic sepsis , were monitored . Survival was calculated by the Kaplan-Meier method . All statistical tests were two-sided . RESULTS The delivered median dose intensity was 99 % ( interquartile range = 96%-100 % ) for the st and ard arm and 182 % ( interquartile range = 163%-196 % ) for the dose-dense arm . After a median follow-up of 14 months , overall response to treatment was observed in 118 ( 80 % ) of the 148 evaluable patients in the st and ard arm and in 129 ( 88 % ) of the 147 evaluable patients in the dose-dense arm , a statistically non-significant difference . Median overall survival was 13.9 months ( 95 % confidence interval [ CI ] = 12.9 to 15.8 months ) in the st and ard arm and 14.4 months ( 95 % CI = 12.7 to 16.0 ) in the dose-dense arm , and the 2-year survival was 22 % ( 95 % CI = 16 % to 29 % ) and 19 % ( 95 % CI = 14 % to 27 % ) , respectively -- neither difference being statistically significant . The median treatment free time was 286 days ( 95 % CI = 229 to 343 days ) for the st and ard arm and 367 days ( 95 % CI = 321 to 413 days ) for the dose-dense arm ( difference = 81 days ; P = .109 ) . Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the st and ard arm , but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the st and ard arm than in the dose-dense arm ( 15.3 % versus 11.6 % , respectively ; difference = 3.7 % , 95 % CI = -4.1 % to 11.5 % ; P = .03 ) . CONCLUSIONS Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did st and ard ICE but did not improve overall survival BACKGROUND The duration of , re sources required for and cost of clinical trials could be reduced if a surrogate end point was to be used in place of survival . We assessed the extent to which the objective response rate ( ORR ) is predictive of mortality , how much difference in the ORR is needed to predict an obvious survival difference and what factors could affect the association between the two parameters during the first-line treatment of extensive disease (ED)-small-cell lung cancer ( SCLC ) . METHODS We used the ORRs and median survival times ( MSTs ) from 48 phase III trials of first-line chemotherapy involving 8779 r and omised patients with ED-SCLC in a linear regression analysis . The MST difference was calculated as the difference in MST between the investigational and reference arms ; the ORR difference was similarly defined . RESULTS ORR difference between the treatment arms was modestly associated with the MST difference in the overall trials ( R(2 ) = 0.3314 ) . In contrast , the relationship was stronger among only trials in which prophylactic cranial irradiation was given to those having an objective response to the initial chemotherapy ( R(2 ) = 0.6279 ) . In this trial setting , large differences in ORR were needed to predict a survival advantage ( 1.2-day survival advantage per 2 % increase in ORR ) . CONCLUSIONS In the first-line treatment of ED-SCLC , a favourable relationship was detected between the two parameters in the selected trial setting . Large ORR differences were needed to predict a survival benefit , clearly suggesting the need for new chemotherapeutic agents PURPOSE The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in " sensitive " ( s ) and " refractory " ( r ) small-cell lung cancer ( SCLC ) patients treated previously . EXPERIMENTAL DESIGN Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study . Patients were enrolled in two separate groups : r group ( patients who failed first-line treatment <3 months from treatment discontinuation ) and s group ( patients who responded to first-line treatment and progressed > or=3 months after treatment discontinuation ) . Cisplatin was given i.v . at the dose of 60 mg/m(2 ) on day 1 , and topotecan was administered as a daily i.v . infusion at the dose of 0.75 mg/m(2 ) from day 1 to 5 , every 3 weeks . RESULTS A total of 110 eligible ( 68 s and 42 r ) patients were enrolled from 24 institutions . The main patient characteristics were as follows : median age 60 ( s ) and 55 ( r ) years , median performance status 1 for both ( s ) and ( r ) . Seventy-four percent ( s ) and 67 % ( r ) had extensive stage disease , including 22 % and 36 % , respectively , with brain metastases . A total of 398 chemotherapy courses were administered [ median 4 ( s ) and 3 ( r ) per patient ] . The most frequent and serious toxicity was myelosuppression . Grade IV neutropenia occurred in 62 % ( s ) and 49 % ( r ) of patients , with a 19 % ( s ) and 15 % ( r ) incidence of febrile neutropenia , and grade IV thrombocytopenia in 54 % ( s ) and 44 % ( r ) . Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and /or delay in the following courses . Grade III-IV nonhematological toxicity was uncommon . Five deaths possibly related to toxicity occurred among s patients only . Objective responses have been documented in 20 s patients , 19 partial responses and 1 complete response , ( 29.4 % response rate ; 95 % confidence interval , 19 - 42 ) , whereas , among r patients , 10 partial responses have been observed ( 23.8 % response rate ; 95 % confidence interval , 12 - 39 ) . Median survival for s and r was 6.4 and 6.1 months , respectively . CONCLUSIONS The combination of cisplatin and topotecan , at this dose and schedule , shows activity and promising results in patients with refractory SCLC , with reversible myelosuppression being the main side effect . Additional development of this regimen , using better-tolerated schedules , is warranted in patients with refractory SCLC BACKGROUND Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide ( TEP ) is very active and well tolerated in patients with small-cell lung cancer ( SCLC ) . In order to compare the TEP combination to cisplatin etoposide ( EP ) regimen as front-line treatment in patients with SCLC , we conducted a r and omised multicenter study . PATIENTS AND METHODS One hundred thirty-three chemotherapy-naïve patients with histologically proven limited or extensive stage SCLC were r and omised to receive either paclitaxel 175 mg/m2 i.v . three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v . on day 2 and etoposide 80 mg/m2 i.v . on days 2 - 4 with G-CSF support ( 5 mcg/kg s.c . days 5 - 15 ) or cisplatin 80 mg/m2 i.v . on day 1 and etoposide 120 mg/m2 i.v . on days 1 - 3 in cycles every twenty-eight days . RESULTS Due to excessive toxicity and mortality observed in the TEP arm , an early interim analysis was performed and the study was closed . Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age , sex , performance status , stage of disease and the presence of abnormal LDH at diagnosis . In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50 % ( 95 % confidence interval ( CI ) : 37.5%-62.4 % ) for TEP and 48 % ( 95 % ) CI : 36.2%-59.5 % ) for EP ( P = 0.8 ) . The median time to disease progression was 11 months for TEP and 9 months for EP ( P = 0.02 ) . The duration of response , one-year survival and overall survival were similar in the two arms . Similarly , in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease , there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen , eight versus six months ( P = 0.04 ) . However , there were eight toxic deaths in the TEP arm versus none in the EP arm ( P = 0.001 ) . Moreover , the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia ( P = 0.04 ) , grade 3 - 4 thrombocytopenia ( P = 0.02 ) , febrile neutropenia ( P = 0.08 ) , grade 3 - 4 diarrhea ( P = 0.01 ) , grade 3 - 4 asthenia ( P = 0.05 ) and grade 3 neurotoxicity ( P = 0.06 ) . CONCLUSIONS In this early terminated study , the TEP regimen was significantly more toxic than the EP regimen . The TEP regimen is associated with significant toxicity and mortality , and should not be used outside of a protocol setting . For future investigations , dose and schedule modifications are necessary to reduce toxicity BACKGROUND This phase II study evaluated the efficacy and safety of the irinotecan/gemcitabine combination in patients with relapsed/refractory small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Patients with measurable tumor who had received one previous chemotherapy or chemotherapy/radiation regimen were eligible . Gemcitabine 1000 mg/m(2 ) was administered i.v . over 30 min followed immediately by irinotecan 100 mg/m(2 ) i.v . over 90 min , both on days 1 and 8 every 21 days . Patients were stratified based on response to initial treatment [ i.e. primary sensitive disease with progression > or=3 months ( group A ) , or refractory disease ( group B ) ] . RESULTS Seventy-three patients were enrolled but one never received treatment and one ineligible patient did not have SCLC . Median patient ages of the remaining patients were 61 and 63 years in groups A ( n = 35 ) and B ( n = 36 ) , respectively , with performance status of 0 or 1 in 85 % of 71 patients . Primary grade 3/4 toxic effects in groups A versus B were neutropenia ( 36 % versus 43 % ) , thrombocytopenia ( 36 % versus 26 % ) , nausea ( 12 % versus 11 % ) , vomiting ( 0 versus 11 % ) , diarrhea ( 12 % versus 9 % ) , and pulmonary ( 12 % versus 12 % ) . Two patients had fatal events including pneumonitis ( n = 1 ) and acute respiratory distress syndrome ( n = 1 ) . Responses occurred in 11 group A [ two complete responses and nine partial responses ( PRs ) ] and four group B ( all PRs ) patients , for response rates of 31 % [ 95 % confidence interval ( CI ) 17 % , 49 % ) and 11 % ( 95 % CI 3 % , 26 % ) , respectively . Median survival and progression-free survival times were 7.1 ( 95 % CI 6 , 10.5 ) versus 3.5 ( 95 % CI 3.1 , 5.7 ) months , and 3.1 ( 95 % CI 1.6 , 5.3 ) versus 1.6 ( 95 % CI 1.4 , 2.8 ) months for group A versus B. CONCLUSION The irinotecan/gemcitabine combination is active and well tolerated as second-line therapy in SCLC patients . Additional studies are warranted as second-line therapy in patients who progressed 90 days or more after first-line therapy . However , the observed efficacy results in refractory SCLC patients indicate that this regimen should not be further explored in this population PURPOSE Irinotecan plus cisplatin ( IP ) improved survival over etoposide plus cisplatin ( EP ) in Japanese patients with extensive-stage small-cell lung cancer ( E-SCLC ) . To confirm those results and discern the potential role of population -related pharmacogenomics ( PG ) in outcomes , we conducted a large r and omized trial of identical design to the Japanese trial in North American patients with E-SCLC . PATIENTS AND METHODS Patients were r and omly assigned to IP ( irinotecan 60 mg/m(2 ) on days 1 , 8 , and 15 ; cisplatin 60 mg/m(2 ) day 1 , every 4 weeks ) or EP ( etoposide 100 mg/m(2 ) on days 1 through 3 ; cisplatin 80 mg/m(2 ) day 1 , every 3 weeks ) . Blood specimens for genomic DNA analysis were collected before r and om assignment in 169 patients . RESULTS Of 671 patients , 651 were eligible ( 324 and 327 patients in the IP and EP arms , respectively ) . Response rates with IP and EP were 60 % and 57 % , respectively ( P = .56 ) . Median progression-free survival for IP and EP was 5.8 and 5.2 months , respectively ( P = .07 ) . Median overall survival for IP and EP was 9.9 and 9.1 months , respectively ( P = .71 ) . Severe diarrhea was more common with IP ( 19 % v 3 % ) ; severe neutropenia and thrombocytopenia were higher with EP versus IP ( 68 % v 33 % and 15 % v 4 % , respectively ) . PG analysis showed that ABCB1 (C3435T)T/T ( membrane transport ) was associated with IP-related diarrhea ; UGT1A1 (G-3156A)A/A ( drug metabolism ) was associated with IP-related neutropenia . CONCLUSION This large North American trial failed to confirm the previously reported survival benefit observed with IP in Japanese patients . Both regimens produced comparable efficacy , with less hematologic and greater gastrointestinal toxicity with IP . These results emphasize the potential importance of PG in interpreting trials of cancer therapy We examined the safety and efficacy of the combination of irinotecan plus carboplatin in patients with refractory or relapsed small cell lung cancer ( SCLC ) . Patients with previously treated SCLC were eligible . Patients were treated every 3 weeks with carboplatin ( with a target area under the concentration versus time curve of 5 mg min/ml using the Calvert formula on day 1 ) plus irinotecan ( 50 mg/m(2 ) on days 1 and 8) . From May 2000 to January 2002 , 24 patients were eligible . None of the 22 patients achieved a complete response , but 15 achieved a partial response with an overall response rate of 68.2 % ( 95 % confidence interval , 45.1 - 86.1 % ) . In 13 patients with sensitive disease , the response rate was 92.3 % ( 95 % confidence interval , 64.0 - 99.8 % ) . The median survival time ( MST ) was 194 days ( range 27 - 605 days ) . The MST did not differ significantly between patients with sensitive disease ( 245 days ) and those with refractory disease ( 194 days , P=0.88 ) . One patient died of treatment-related sepsis . Grade 3 - 4 hematologic toxicities included leukopenia in 58 % of patients , neutropenia in 63 % , thrombocytopenia in 58 % , and anemia in 67 % . Grade 3 diarrhea developed in 21 % of patients and grade 3 - 4 infection in 13 % . No patients had grade 4 diarrhea or grade 3 - 4 nausea and vomiting . This regimen is effective and well tolerated in patients with relapsed or refractory SCLC . However , the search for even more active regimens should be continued BACKGROUND Etoposide plus cisplatin ( EP ) is a st and ard combination chemotherapy regimen for small cell lung cancer ( SCLC ) . The objective of this r and omized trial is to compare the efficacy and toxicity of combined chemotherapy regimen of irinotecan plus cisplatin ( IP ) with the EP regimen in the treatment of SCLC . METHODS A r and omized clinical trial was conducted in which the IP regimen was compared with EP regimen in the treatment of patients with SCLC . A total of 61 patients were r and omly divided into IP group ( n=30 ) and EP group ( n=31 ) . All patients were given more than two chemotherapy cycles . RESULTS (1)The overall response rate was 66.7 % in IP group and 61.3 % in EP group respectively . The complete response was 23.3 % in IP group and 16.1 % in EP group . There was no significant difference in the response rate between the two groups ( P > 0.05 ) . (2)Severe or life-threatening myelosuppressions such as leucopenia , neutropenia and thrombocytopenia were more frequent in EP group than those in IP group ( P < 0.01 ) , and severe diarrhea was more frequent in IP group than that in EP group , and there was significant statistical difference ( P=0.008 ) . CONCLUSIONS IP regimen is an effective regimen for SCLC . Compared with EP regimen , IP regimen has less hematological toxicities but higher diarrhea incidence . The diarrhea of irinotecan can be controlled by appropriate treatment PURPOSE To determine , in a r and omized comparison , whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer ( SCLC ) compared with st and ard etoposide and cisplatin and to compare the regimens ' toxicity . PATIENTS AND METHODS Eligible patients ( N=587 ) with untreated extensive SCLC were r and omly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles ( EP ) or cisplatin 80 mg/m2 on day 1 , paclitaxel 175 mg/m2 over 4 hours on day 1 , and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles ( PET ) . RESULTS Reporting of demographics , response , and survival included 565 patients , of whom 282 were r and omly assigned to receive EP and 283 were assigned to receive PET . Overall response rates were 68 % for the EP arm and 75 % for the PET arm . Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm ( P = .179 ) . Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET ( P = .169 ) . Toxic deaths occurred in 2.4 % of the patients on EP and 6.5 % of patients on PET . CONCLUSION PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity PURPOSE A Japanese r and omized trial showed superior survival for patients with extensive-disease ( ED ) small-cell lung cancer ( SCLC ) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin . The present trial evaluated the efficacy of irinotecan plus carboplatin ( IC ) compared with oral etoposide plus carboplatin ( EC ) . PATIENTS AND METHODS Patients with ED SCLC were r and omly assigned to receive either IC , which consisted of carboplatin ( area under the curve = 4 ; Chatelut formula ) and irinotecan ( 175 mg/m2 ) intravenously both on day 1 , or EC , which consisted of carboplatin as in IC and etoposide ( 120 mg/m(2)/d ) orally on days 1 through 5 . Courses were repeated every 3 weeks with four cycles planned . Doses were reduced by one third in patients with a WHO performance status ( PS ) of 3 to 4 and /or age older than 70 years . Primary end point was overall survival ( OS ) . Secondary end points were quality of life ( QOL ) and complete response ( CR ) rate . RESULTS Of 220 r and omly assigned patients , 209 were eligible for analysis ( IC , n = 105 ; EC , n = 104 ) . Thirty-five percent were older than 70 years , and 47 % had a PS of 2 to 4 . The groups were well balanced with respect to prognostic factors . OS was inferior in the EC group ( hazard ratio = 1.41 ; 95 % CI , 1.06 to 1.87 ; P = .02 ) . Median survival time was 8.5 months for IC compared with 7.1 months for EC . One-year survival rate was 34 % for IC and 24 % for EC . CR was seen in 18 IC patients compared with seven EC patients ( P = .02 ) . There were no statistically significant differences in hematologic grade 3 or 4 toxicity . Grade 3 or 4 diarrhea was more common in the IC group . QOL differences were small , with a trend toward prolonged palliation with the IC regimen . CONCLUSION IC prolongs survival in ED SCLC with slightly better scores for QOL 8029 Background : Superiority of irinotecan over etoposide in combination with cis- or carboplatin was demonstrated in a Japanese and a Sc and inavian phase III trial . However , both cisplatin-based North American phase III studies could not detect any difference in efficacy . We report the final results of the German r and omized phase III trial comparing etoposide/carboplatin ( PE ) to irinotecan/carboplatin ( IP ) in small cell lung cancer ( SCLC ) extensive disease . METHODS Chemotherapy-naïve extensive disease SCLC patients were r and omly assigned to receive carboplatin AUC 5 mg × min/mL either in combination with 50 mg/m2 of irinotecan on days 1 , 8 and 15 ( IP , Arm A ) or with etoposide 140mg/m2 days 1 - 3 ( EP ) . IP treatment was repeated every 4 weeks , EP every 3 weeks . Response assessment was performed after cycles 2 , 4 and 6 and every 3 months thereafter . Toxicity was assessed once weekly . Primary endpoint was detection of progression free survival ( PFS ) , secondary endpoints were overall survival ( OS ) , response rate , and toxicity . RESULTS A total of 216 patients from 8 centres were r and omized . No significant differences in survival or response rate could be detected . Median PFS was 6 months in both arms . Median OS was 10 months ( 95 % confidence interval ( CI ) 8.3 -11.7 ) in the IP arm and 9 months ( 95 % CI 7.6 -10.4 ) in the EP arm . 1 year survival was 37 % ( 95 % CI 25.6 - 47.6 ) and 28 % ( 95 % CI 18.2 - 37.4 ) in the IP and EP arm . 62 % of patients in the IP and 63 % in the EP arm had a confirmed complete or partial remission according to RECIST criteria . Significant differences in grade 3 and 4 toxicity were observed for thrombopenia ( 22 % IP vs 47 % EP ) and neutropenia ( 23 % IP vs 61 % PE ) without differences in the rate of febrile neutropenia . Grade 3 and 4 diarrhea was manageable and as expected significantly more frequent with IP ( 15 % ) than with EP ( 6 % ) . CONCLUSIONS Our phase III trial shows equivalent efficacy of irinotecan when compared to etoposide in combination with carboplatin . [ Table : see text ] BACKGROUND Irinotecan hydrochloride , a topoisomerase I inhibitor , is effective against small-cell lung cancer . In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer , there was a high response rate and a promising median survival time . METHODS We conducted a multicenter , r and omized , phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive ( metastatic ) small-cell lung cancer . RESULTS The planned size of the study population was 230 patients , but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin ; as a result , only 154 patients were enrolled . The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group ( P=0.002 by the unadjusted log-rank test ) . At two years , the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group . Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group , and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group . CONCLUSIONS Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer PURPOSE Etoposide and cisplatin ( EP ) has been a st and ard treatment for extensive-disease small-cell lung cancer ( SCLC ) . An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin ( IP ) versus EP . Our trial was design ed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP . PATIENTS AND METHODS The primary objective was to compare overall survival in extensive-disease SCLC patients r and omly assigned to receive IP ( n = 221 ) or EP ( n = 110 ) . Patients were r and omly assigned in 2:1 ratio to cisplatin 30 mg/m2 intravenously ( IV ) + irinotecan 65 mg/m2 IV on days 1 and 8 every 21 days , or cisplatin 60 mg/m2 IV on day 1 , and etoposide 120 mg/m2 IV on days 1 to 3 every 21 days for at least four cycles , until progressive disease , or until intolerable toxicity result ed . RESULTS Selected grade 3/4 toxicities for IP/EP were : neutropenia ( 36.2 % v 86.5 % ; P < .01 ) , febrile neutropenia ( 3.7 % v 10.4 % ; P = .06 ) , anemia ( 4.8 % v 11.5 % ; P = .02 ) , thrombocytopenia ( 4.3 % v 19.2 % ; P < .01 ) , vomiting ( 12.5 % v 3.8 % ; P = .04 ) , and diarrhea ( 21.3 % v 0 % ; P < .01 ) . There was no significant difference in response rates ( 48 % v 43.6 % ) , median time to progression ( 4.1 v 4.6 months ) , or overall survival ( median survival time , 9.3 months v 10.2 months ; P = .74 ) . CONCLUSION Treatment with this dose and schedule of IP did not result in improved survival when compared with EP . Fewer patients receiving IP had grade 3/4 anemia , thrombocytopenia , neutropenia , and febrile neutropenia compared with patients receiving EP , but more had grade 3/4 diarrhea and vomiting We design ed a phase II study of weekly irinotecan ( CPT-11 ) and carboplatin for refractory or relapsed small cell lung cancer ( SCLC ) and assessed the response rate , survival , and toxicity . Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial . The median time off chemotherapy was 3.5 months ( range : 0.8 - 12.9 ) . Patients were treated at 4-week intervals using CPT-11 ( 50 mg/m(2 ) intravenously on days 1 , 8 and 15 ) plus carboplatin ( AUC = 2 mg/ml min , intravenously on days 1 , 8 , 15 ) . All patients were assessable for toxicity and survival ; 28 patients were assessable for response . There were nine partial responses ( PRs ) . Overall response rate was 31.0 % ( 95 % CI : 15.3 - 50.8 % ) . The median time to progression was 3.5 months . Median survival time was 6.1 months . Major toxicity was myelosuppression . Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21 % of patients , respectively . Grade 3 - 4 diarrhea was observed in 7 % . There was one treatment-related death due to febrile neutropenia and sepsis . This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer PURPOSE This open-label , r and omized , multicenter phase III study compared oral topotecan/intravenous cisplatin ( TC ) with intravenous ( IV ) etoposide/cisplatin ( PE ) in patients with untreated extensive-disease small-cell lung cancer ( ED-SCLC ) . PATIENTS AND METHODS A total of 784 patients were r and omly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 ( n = 389 ) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 ( n = 395 ) every 21 days . RESULTS Overall survival ( primary end point ) was similar between groups ( P = .48 ; median : TC , 39.3 weeks v PE , 40.3 weeks ) . One-year survival was 31 % ( 95 % CI , 27 % to 36 % ) in both groups and the difference of -0.03 ( 95 % CI , -6.53 to 6.47 ) met the predefined criteria of < or = 10 % absolute difference for noninferiority of TC relative to PE . Response rates were similar between groups ( TC , 63 % v PE , 69 % ) . Time to progression was slightly but statistically longer with PE ( log-rank P = .02 ; median : TC , 24.1 weeks v PE , 25.1 weeks ) . The regimens were similarly tolerable . Grade 3/4 neutropenia occurred more frequently with PE ( 84 % v 59 % ) , whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC ( 38 % v 21 % and 38 % v 23 % , respectively ) . Lung Cancer Symptom Scale scores were statistically better with PE , but the differences were small and of debatable clinical significance . CONCLUSION Oral topotecan with cisplatin provides similar efficacy and tolerability to the st and ard ( etoposide with cisplatin ) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin PURPOSE To evaluate the activity of CPT-11 , which is a new derivative of camptothecin , against refractory or relapsed small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Sixteen patients with refractory or relapsed SCLC were entered onto a prospect i ve , non-r and omized , single-institution phase II trial . All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy . Five patients had received previous chemotherapy with cisplatin , vincristine , doxorubicin , and etoposide ( CODE ) as an induction therapy . Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray . The median time off chemotherapy was 7.3 months ( range , 1.9 to 15.1 months ) . Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous ( IV ) infusion every week with subsequent doses based on toxicity . Fifteen patients were assessable for toxicity , response , and survival . RESULTS Seven patients ( 47 % ; 95 % confidence limits for an overall response rate , 21.4 % to 71.9 % ) responded to CPT-11 with a median duration of response of 58 days . The major toxicities were myelosuppression ( predominantly leukopenia ) , diarrhea , and pulmonary toxicity . CONCLUSION CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC PURPOSE To evaluate the activity and toxicity of the combination carboplatin plus vinorelbine in extensive small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS A two-stage optimal Simon design was applied . To proceed after the first stage , responses from 8 of 11 treated patients were needed . Overall , 31 responses of 43 treated patients were required to comply with the design parameters . Inclusion criteria were cytohistologically proven SCLC ; extensive disease ; age of 70 years or less ; Eastern Cooperative Oncology group performance status ( ps ECOG ) of 2 or less ; normal cardiac , hepatic , renal , and bone marrow functions ; and no previous chemotherapy . Patients were staged by physical examination ; biochemistry ; chest radiograph ; brain , thoracic ; and abdominal computed tomographic ( CT ) scans , and bone scan . All patients received carboplatin 300 mg/m2 intravenously ( i.v . ) day 1 and vinorelbine 25 mg/m2 i.v . on days 1 and 8 every 4 weeks up to six cycles . Of 43 enrolled patients , 36 were men and 7 women , with a median age of 63 years ( range , 46 to 70 years ) . RESULTS All patients were assessable for response and toxicity . We observed 32 ( 74 % ) objective responses , with 23 % complete responses . Median time to progression was 25 weeks , and median survival was 37 weeks . The treatment was well tolerated . The reported main toxicities were leukopenia grade 3 in 21 % of patients and grade 4 in 5 % of patients , anemia grade 2 in 11 % of patients and grade 3 in 2 % of patients , and thrombocytopenia grade 3 in 7 % of patients . CONCLUSION These data show that carboplatin plus vinorelbine is an active and well-tolerated regimen in extensive SCLC . In view of the activity , low toxicity , and ease of administration , it may be a reasonable alternative to more toxic cisplatin-containing regimens BACKGROUND It is unclear whether etoposide/cisplatin ( EP ) regimen is the optimal chemotherapy regimen in the treatment patients with extensive small cell lung cancer ( SCLC ) , this study was aim ed to evaluate the efficacy and safety of patients with extensive SCLC treated with irinotecan/cisplatin ( IP ) versus EP . METHODS We search ed EMBASE , PubMed , the Cochrane Library , China journal full-text data base ( CJFD ) , Chinese scientific journal full-text data base ( CSJD ) , Chinese biomedicine literature data base ( CBM ) for r and omized controlled trials comparing IP with EP regimens . Two review ers independently assessed the quality of included studies and extracted data . We analyzed the data using Review Manager ( version 5.0 ) . RESULTS Four r and omized controlled trials totaling 1 180 patients were included . The results of meta analysis were as follows : there was no significant difference between IP regimen and EP regimens in one year survive rate ( RR=1.22 , 95%CI : 0.97 - 1.54 ) , two year survive rate ( RR=2.26 , 95%CI : 0.46 - 11.21 ) . There was significant difference between IP regimen and EP regimens in overall response rate ( RR=1.13 , 95%CI : 1.03 - 1.25 ) , grade 3/4 neutropenia ( RR=0.48 , 95%CI : 0.34 - 0.69 ) , thrombopenia ( RR=0.23 , 95%CI : 0.15 - 0.36 ) , grade 3 anemia ( RR=0.55 , 95%CI : 0.40 - 0.77 ) , grade 3/4 diarrhea ( RR=9.56 , 95%CI : 4.91 - 18.59 ) , grade 3 nausea/vomiting ( RR=1.70 , 95%CI : 1.19 - 2.43 ) . CONCLUSIONS There is no significant difference between IP group and EP group with regard to one year survive rate , two year survive rate , but IP regimen improves reponse rate . IP regimen has less hematologic & greater gastrointestinal toxicity compared with EP , EP regimen remain the main st and ard chemotherapy in the treatment extensive small cell lung cancer due to cheapness , they still need to be confirmed by r and omized controlled trials BACKGROUND Topotecan is one of active agents for relapsed small cell lung can-cer ( SCLC ) , some studies have shown that it is effective against SCLC as the first-line drug . This study is to assess the efficacy , toxicity and survival rate of topotecan plus cisplatin ( TP ) versus etoposide plus carboplatin ( CE ) in patients with previously untreated SCLC . METHODS Sixty-four patients with previously untreated SCLC were r and omly assigned to receive either TP or CE . Topotecan 0.75 mg/(m² × d ) via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/(m² × d ) on days 1 to 3 with hydration were given to patients in TP group . Carboplatin 300 mg/m² on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group . Treatment was repeated every 21 days . Responses and toxicities were evaluated in patients who received two cycles of chemotherapy . Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy . RESULTS Overall response rate was 75.0 % in TP group and 68.8 % in CE group . The median survival time was 10.5 months in TP group and 9.6 months in CE group . 1- , 2- and 3-year survival rate were 40.6 % , 18.8 % and 9.4 % in TP group and 34.4 % , 15.6 % and 9.4 % in CE group respectively . There were no significant differences in response rate , median survival time and survival rate between two groups ( P > 0.05 ) . Myelosuppression , nausea and vomiting , and alopecia were the most common toxicities , there was no significant difference in grade III and IV toxicities between two groups ( P > 0.05 ) . CONCLUSIONS TP has similar response rate and survivals with CE , and its toxicities are acceptable . TP regimen is an effective first-line treatment for SCLC A Phase II study of CPT-11 , a new camptothecin , was performed in patients with primary lung cancer . Patients with previously untreated non-small cell carcinomas ( group A ) , or previously treated non-small cell carcinomas ( group B ) , and with small cell carcinomas ( group C ) , were enrolled in this study . CPT-11 was given at a dose of 100 mg/m2 i.v . infusion once a week for three weeks or more . Out of 153 patients enrolled , 128 ( A : 67 ; B : 26 ; C : 35 ) were assessed to be evaluable for response by an extramural review committee . Response rates were 34.3 % ( 23/67 ) for A , 0 % ( 0/26 ) for B and 37.1 % ( 13/35 ) for C. The response rate was 50 % for previously untreated patients ( 4/8 ) , and 33.3 % for previously treated patients ( 9/27 ) including 2 complete responses in the group C. Major toxicities were leukopenia , nausea/vomiting , diarrhea , anorexia and alopecia . Leukopenia and diarrhea were considered to be dose limiting toxicities , but they were reversible . It was , however , suggested that some patients should be monitored carefully for severe reactions and delay in recovery . The results showed that CPT-11 was highly effective against non-small cell and small cell carcinomas of the lung BACKGROUND A combination of irinotecan ( CPT-11 ) and cisplatin ( CDDP ) was shown to be effective for extensive-disease small-cell lung cancer ( ED-SCLC ) . To take maximum advantage of the synergistic effect between CPT-11 and CDDP , we design ed a fractionated administration schedule . PATIENTS AND METHODS Between August 1995 and September 1998 , 15 previously untreated patients with ED-SCLC were enrolled . Both CPT-11 at a dose of 50 mg/m2 and CDDP at a dose of 60 mg/m2 were given on days 1 and 8 , and repeated every 4 weeks up to four cycles . RESULTS Fifteen patients were assessed for response and survival , and fourteen for toxicity . Although twelve patients ( 80.0 % ; 95 % confidence interval , 51.9 - 95.7 ) achieved an objective response , complete response ( CR ) was not obtained . The median survival time and the actual 1-year survival rate were 9.4 months and 40.0 % , respectively . Grade 3 or 4 leukopenia , neutropenia and diarrhea occurred in 71.4 % , 100 % and 14.3 % of the patients , respectively . Enrollment into this study was stopped because CR , which was the primary endpoint , was not obtained in the consecutive 15 patients and the survival appeared to be inferior to the previous multi-institutional study ( Kudoh et al , Clin Oncol 16 : 1068 - 1074 , 1998 ) . The projected dose intensity in the present study was lower in CPT-11 and higher in CDDP compared to that in the previous report . CONCLUSION These results suggest that the dose intensity of CPT-11 may have a major role on the activity of SCLC in this combination PURPOSE Single-agent intravenous ( IV ) topotecan is an effective treatment for small-cell lung cancer ( SCLC ) after failure of first-line chemotherapy . This open-label , r and omized , phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy . PATIENTS AND METHODS Patients with limited- or extensive-disease SCLC , documented complete or partial response to first-line therapy , Eastern Cooperative Oncology Group performance status < or = 2 , and measurable recurrent disease ( WHO criteria ) with a treatment-free interval of > or = 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days . Primary end point was response rate as confirmed by an external review er blinded to treatment . RESULTS A total of 309 patients were r and omly assigned . In intent-to-treat analysis , response rates were 18.3 % with oral topotecan ( n = 153 ) and 21.9 % with IV topotecan ( n = 151 ) , with a difference ( oral -IV ) of -3.6 % ( 95 % CI , -12.6 % to 5.5 % ) . Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan ; 1- and 2-year survival rates were 32.6 % and 12.4 % for oral topotecan , respectively , and 29.2 % and 7.1 % for IV topotecan , respectively . Third-line chemotherapy was similar for both groups ( 33 % for oral ; 35 % for IV ) . Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows : neutropenia in 47 % and 64 % , thrombocytopenia in 29 % and 18 % , grade 3 or 4 anemia in 23 % and 31 % , and sepsis in 3 % and 3 % , respectively . The most frequent nonhematologic adverse events ( all grade s ) included nausea ( 43 % oral ; 42 % IV ) , alopecia ( 26 % oral ; 30 % IV ) , fatigue ( 31 % oral ; 36 % IV ) , and diarrhea ( 36 % oral ; 20 % IV ) . CONCLUSION Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy |
583 | 30,339,667 | LA countries are targeting SSB consumption through a variety of mechanisms , particularly via restrictions to availability in schools and through taxes . | BACKGROUND AND OBJECTIVES Latin American ( LA ) countries have begun to adopt a variety of regulations targeting sugar-sweetened beverages ( SSBs ) for public health reasons .
Our objective was to characterize the regulatory strategies design ed to reduce SSB consumption over the last decade , and assess the available evidence on their enforcement and impact . | Background Front of pack food labels or signpost labels are currently widely discussed as means to help consumers to make informed food choices . It is hoped that more informed food choices will result in an overall healthier diet . There is only limited evidence , as to which format of a food label is best understood by consumers , helps them best to differentiate between more or less healthy food and whether these changes in perceived healthiness result in changes of food choice . Methods In a r and omised experimental study in Hamburg/Germany 420 adult subjects were exposed to one of five experimental conditions : ( 1 ) a simple " healthy choice " tick , ( 2 ) a multiple traffic light label , ( 3 ) a monochrome Guideline Daily Amount ( GDA ) label , ( 4 ) a coloured GDA label and ( 5 ) a " no label " condition . In the first task they had to identify the healthier food items in 28 pair-wise comparisons of foods from different food groups . In the second task they were asked to select food portions from a range of foods to compose a one-day 's consumption . Differences between means were analysed using ANOVAs . Results Task I : Experimental conditions differed significantly in the number of correct decisions ( p < 0.001 ) . In the condition " no label " subjects had least correct decisions ( 20.2 ± 3.2 ) , in the traffic light condition most correct decisions were made ( 24.8 ± 2.4 ) . Task II : Envisaged daily food consumption did not differ significantly between the experimental conditions . Conclusion Different food label formats differ in the underst and ing of consumers . The current study shows , that German adults profit most from the multiple traffic light labels . Perceived healthiness of foods is influenced by this label format most often . Nevertheless , such changes in perceived healthiness are unlikely to influence food choice and consumption . Attempts to establish the informed consumer with the hope that informed choices will be healthier choices are unlikely to change consumer behaviour and will not result in the desired contribution to the prevention of obesity and diet related diseases Background : Brazil is currently debating the implementation of front-of-package labels . This study tested if Warning labels ( WLs ) improved consumer underst and ing , perceptions , and purchase intentions compared to Traffic-Light labels ( TLLs ) in 1607 Brazilian adults . Methods : In this online , r and omized controlled experiment participants saw images of 10 products and answered questions twice — once in a no-label , control condition and then again in a r and omly assigned label condition . The relative differences in responses between WLs and TLLs between control and label conditions were estimated using one-way ANOVAs or Chi-square tests . Results : Presenting WLs on products compared to TLLs helped participants : ( i ) improve their underst and ing of excess nutrient content ( 27.0 % versus 8.2 % , p < 0.001 ) ; ( ii ) improve their ability to identify the healthier product ( 24.6 % versus 3.3 % , p < 0.001 ) ; ( iii ) decrease perceptions of product healthfulness ; and ( iv ) correctly identify healthier products ( 14.0 % versus 6.9 % , p < 0.001 ) , relative to the control condition . With WLs , there was also an increase in the percentage of people : ( v ) expressing an intention to purchase the relatively healthier option ( 16.1 % versus 9.8 % , p < 0.001 ) ; and ( vi ) choosing not to buy either product ( 13.0 % versus 2.9 % , p < 0.001 ) , relative to the control condition . The participants in the WL condition had significantly more favorable opinions of the labels compared to those in the TLL group . Conclusions : WLs would be more effective , compared to the TLL , at improving consumer food choices |
584 | 32,122,378 | The cost savings to the healthcare setting identified in these studies outweighed the cost of the collaborative itself .
Potential cost savings to the health care system in both acute and chronic conditions may be possible by applying QICs at scale .
Consistent identification of costs and description of the elements applied in QICs would better inform decisions for their use and may reduce perceived barriers . | In increasingly constrained healthcare budgets worldwide , efforts to improve quality and reduce costs are vital .
Quality Improvement Collaboratives ( QICs ) are often used in healthcare setting s to implement proven clinical interventions within local and national programs .
The cost of this method of implementation , however , is cited as a barrier to use .
This systematic review aims to identify and describe studies reporting on costs and cost-effectiveness of QICs when used to implement clinical guidelines in healthcare . | Objective : To investigate the lifelong health effects , costs , and cost-effectiveness of a quality improvement collaborative focusing on improving diabetes management in an integrated care setting . Study Design and Methods : Economic evaluation from a healthcare perspective with lifetime horizon alongside a nonr and omized , controlled , before-after study in the Netherl and s. Analyses were based on 1861 diabetes patients in 6 intervention and 9 control regions , representing 37 general practice s and 13 out-patient clinics . Change in the United Kingdom Prospect i ve Diabetes Study score , remaining lifetime , and costs per quality -adjusted life year gained were calculated . Probabilistic life tables were constructed using the United Kingdom Prospect i ve Diabetes Study risk engine , a vali date d diabetes model , and nonparametric bootstrapping of individual patient data . Results : Annual United Kingdom Prospect i ve Diabetes Study risk scores reduced for cardiovascular events ( hazard ratio : 0.83 and 0.98 ) and cardiovascular mortality ( hazard ratio : 0.78 and 0.88 ) for men and women , respectively . Life expectancy improved by 0.97 and 0.76 years for men and women , and quality -adjusted life years by 0.44 and 0.37 , respectively . Higher life expectancy in the intervention group increased lifelong costs by & OV0556;860 for men and & OV0556;645 for women . Initial program costs were about & OV0556;22 per patient . The incremental costs per quality -adjusted life year were & OV0556;1937 for men and & OV0556;1751 for women compared with usual care costs . There is a probability > 95 % that the collaborative is cost-effective , using a threshold of & OV0556;20,000 per quality -adjusted life year . Conclusion : Optimizing integrated and patient-centered diabetes care through a quality -improvement collaborative is cost-effective compared with usual care Background Quality improvement collaboratives ( QIC ) have proliferated internationally , but there is little empirical evidence for their effectiveness . Method We search ed Medline , Embase , CINAHL , PsycINFO and the Cochrane Library data bases from January 1995 to December 2014 . Studies were included if they met the criteria for a QIC intervention and the Cochrane Effective Practice and Organisation of Care ( EPOC ) minimum study design characteristics for inclusion in a review . We assessed study bias using the EPOC checklist and the quality of the reported intervention using a subset of SQUIRE 1.0 st and ards . Results Of the 220 studies meeting QIC criteria , 64 met EPOC study design st and ards for inclusion . There were 10 cluster r and omised controlled trials , 24 controlled before-after studies and 30 interrupted time series studies . QICs encompassed a broad range of clinical setting s , topics and population s ranging from neonates to the elderly . Few reports fully described QIC implementation and methods , intensity of activities , degree of site engagement and important context ual factors . By care setting , an improvement was reported for one or more of the study ’s primary effect measures in 83 % of the studies ( 32/39 ( 82 % ) hospital based , 17/20 ( 85 % ) ambulatory care , 3/4 nursing home and a sole ambulance QIC ) . Eight studies described persistence of the intervention effect 6 months to 2 years after the end of the collaborative . Collaboratives reporting success generally addressed relatively straightforward aspects of care , had a strong evidence base and noted a clear evidence - practice gap in an accepted clinical pathway or guideline . Conclusions QICs have been adopted widely as an approach to shared learning and improvement in healthcare . Overall , the QICs included in this review reported significant improvements in targeted clinical processes and patient outcomes . These reports are encouraging , but most be interpreted cautiously since fewer than a third met established quality and reporting criteria , and publication bias is likely AIMS Improvement collaboratives consisting of various components are used throughout health care to improve quality , but no study has identified which components work best . This study tested the effectiveness of different components in addiction treatment services , hypothesizing that a combination of all components would be most effective . DESIGN An unblinded cluster-r and omized trial assigned clinics to one of four groups : interest circle calls ( group teleconferences ) , clinic-level coaching , learning sessions ( large face-to-face meetings ) and a combination of all three . Interest circle calls functioned as a minimal intervention comparison group . SETTING Out-patient addiction treatment clinics in the United States . PARTICIPANTS Two hundred and one clinics in five states . MEASUREMENTS Clinic data managers su bmi tted data on three primary outcomes : waiting-time ( mean days between first contact and first treatment ) , retention ( percentage of patients retained from first to fourth treatment session ) and annual number of new patients . State and group costs were collected for a cost-effectiveness analysis . FINDINGS Waiting-time declined significantly for three groups : coaching ( an average of 4.6 days/clinic , P = 0.001 ) , learning sessions ( 3.5 days/clinic , P = 0.012 ) and the combination ( 4.7 days/clinic , P = 0.001 ) . The coaching and combination groups increased significantly the number of new patients ( 19.5 % , P = 0.028 ; 8.9 % , P = 0.029 ; respectively ) . Interest circle calls showed no significant effect on outcomes . None of the groups improved retention significantly . The estimated cost per clinic was $ 2878 for coaching versus $ 7930 for the combination . Coaching and the combination of collaborative components were about equally effective in achieving study aims , but coaching was substantially more cost-effective . CONCLUSIONS When trying to improve the effectiveness of addiction treatment services , clinic-level coaching appears to help improve waiting-time and number of new patients while other components of improvement collaboratives ( interest circles calls and learning sessions ) do not seem to add further value OBJECTIVE To estimate the incremental cost-effectiveness of improving diabetes care with the Health Disparities Collaborative ( HDC ) , a national collaborative quality improvement ( QI ) program conducted in community health centers ( HCs ) . DATA SOURCES / STUDY SETTING Data regarding the impact of the Diabetes HDC program came from a serial cross-sectional follow-up study ( 1998 , 2000 , 2002 ) of the program in 17 Midwestern HCs . Data inputs for the simulation model of diabetes came from the latest clinical trials and epidemiological studies . STUDY DESIGN We conducted a societal cost-effectiveness analysis , incorporating data from QI program evaluation into a Monte Carlo simulation model of diabetes . DATA COLLECTION / EXTRACTION METHODS Data on diabetes care processes and risk factor levels were extracted from medical charts of r and omly selected patients . PRINCIPAL FINDINGS From 1998 to 2002 , multiple processes of care ( e.g. , glycosylated hemoglobin testing [ HbA1C ] [ 71 - ->92 percent ] and ACE inhibitor prescribing [ 33 - ->55 percent ] ) and risk factor levels ( e.g. , 1998 mean HbA1C 8.53 percent , mean difference 0.45 percent [ 95 percent confidence intervals -0.72 , -0.17 ] ) improved significantly . With these improvements , the HDC was estimated to reduce the lifetime incidence of blindness ( 17 - ->15 percent ) , end-stage renal disease ( 18 - ->15 percent ) , and coronary artery disease ( 28 - ->24 percent ) . The average improvement in quality -adjusted life year ( QALY ) was 0.35 and the incremental cost-effectiveness ratio was $ 33,386/QALY . CONCLUSIONS During the first 4 years of the HDC , multiple improvements in diabetes care were observed . If these improvements are maintained or enhanced over the lifetime of patients , the HDC program will be cost-effective for society based on traditionally accepted thresholds OBJECTIVE To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model . DESIGN Interventional study . Data on treatment costs were collected for infants with birth weight 501 to 1500 g for the period of January 1 , 1994 to December 31 , 1997 . Data on re sources expended by hospitals to conduct this project were collected in a survey for the period January 1 , 1995 to December 31 , 1996 . SETTING Ten self-selected neonatal intensive care units ( NICUs ) received the intervention . They formed 2 subgroups ( 6 NICUs working on infection , 4 NICUs working on chronic lung disease ) . Nine other NICUs served as a contemporaneous comparison group . PATIENTS Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group ( N = 2993 ) and the 9 comparison NICUs ( N = 2203 ) ; infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group ( N = 663 ) and the 9 comparison NICUs ( N = 1007 ) . INTERVENTIONS NICUs formed multidisciplinary teams which worked together to undertake a collaborative quality improvement effort between January 1995 and December 1996 . They received instruction in quality improvement , review ed performance data , identified common improvement goals , and implemented " potentially better practice s " developed through analysis of the processes of care , literature review , and site visits . MAIN OUTCOME MEASURES Treatment cost per infant is the primary economic outcome measure . In addition , the re sources spent by hospitals in undertaking the collaborative quality improvement effort were determined . RESULTS Between 1994 and 1996 , the median treatment cost per infant with birth weight 501 to 1500 g at the 6 project NICUs in the infection group decreased from $ 57 606 to $ 46 674 ( a statistical decline ) ; at the 4 chronic lung disease hospitals , for infants with birth weights 501 to 1000 g , it decreased from $ 85 959 to $ 77 250 . Treatment costs at hospitals in the control group rose over the same period . There was heterogeneity in the effects among the NICUs in both project groups . Cost savings were maintained in the year following the intervention . On average , hospitals spent $ 68 206 in re sources to undertake the collaborative quality improvement effort between 1995 and 1996 . Two thirds of these costs were incurred in the first year , with the remaining third in the second year . The average savings per hospital in patient care costs for very low birth weight infants in the infection group was $ 2.3 million in the post-intervention year ( 1996 ) . There was considerable heterogeneity in the cost savings across hospitals associated with participation in the collaborative quality improvement project . CONCLUSION Cost savings may be achieved as a result of collaborative quality improvement efforts and when they occur , they appear to be sustainable , at least in the short run . In high-cost patient population s , such as infants with very low birth weights , cost savings can quickly offset institutional expenditures for quality improvement efforts |
585 | 32,275,176 | Discussion : Most of the studies did not show significantly improved overall survival or progression-free survival .
Therefore , there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing . | Introduction : Metronomic dosing is used to give continuous chemotherapy at low doses .
The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease . | BACKGROUND It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer ( NSCLC ) . The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC . METHODS This was a r and omised , controlled , phase 3 trial by the Japan Clinical Oncology Group ( JCOG0301 ) . Patients older than 70 years with unresectable stage III NSCLC were r and omly assigned to chemoradiotherapy ( 60 Gy plus concurrent low-dose carboplatin [ 30 mg/m(2 ) per day , 5 days a week for 20 days ] ) or radiotherapy alone , using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group ( ECOG ) performance status ( 0 vs 1 vs 2 ) , stage ( IIIA vs IIIB ) , and institution . The primary endpoint was overall survival , which was analysed for the eligible population and stratified by ECOG performance status , stage , and institution . The trial was stopped early as a result of the second planned interim analysis . This study is registered with UMIN Clinical Trials Registry , number C000000060 , and Clinical Trials.gov , number NCT00132665 . FINDINGS 200 patients were enrolled from Sept 1 , 2003 to May 27 , 2010 : 100 in the chemoradiotherapy group and 100 in the radiotherapy group . The second planned interim analysis was done 10 months after completion of patient accrual . At this time , median follow-up for censored cases was 19·4 months ( IQR 10·3 - 33·5 ) . In accordance with the prespecified stopping rule , the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group . Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22·4 months ( 95 % CI 16·5 - 33·6 ) and 16·9 months ( 13·4 - 20·3 ) , respectively ( hazard ratio 0·68 , 95·4 % CI 0·47 - 0·98 , stratified log-rank test one-sided p value=0·0179 ) . More patients had grade 3 - 4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group , including leucopenia ( 61 [ 63·5 % ] vs none ) , neutropenia ( 55 [ 57·3 % ] vs none ) , and thrombocytopenia ( 28 [ 29·2 % ] vs two [ 2·0 % ] ) . Grade 3 infection was more common with chemoradiotherapy ( 12 patients [ 12·5 % ] ) than with radiotherapy ( four patients [ 4·1 % ] ) . Incidences of grade 3 - 4 pneumonitis and late lung toxicity were similar between groups . There were seven treatment-related deaths : three of 100 patients ( 3·0 % ) in the chemoradiotherapy group and four of 100 ( 4·0 % ) in the radiotherapy group . INTERPRETATION For a select group of elderly patients with locally advanced NSCLC , combination chemoradiotherapy provides a clinical ly significant benefit over radiotherapy alone , and should be considered for this population . FUNDING Ministry of Health , Labour , and Welfare of Japan Docetaxel plus prednisone is currently the st and ard first‐line treatment in metastatic castration‐resistant prostate cancer ( mCRPC ) . The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients This phase 1 study evaluated the safety and tolerability of antiangiogenic therapy using v and etanib and metronomic cyclophosphamide and methotrexate in metastatic breast cancer . Eligible patients had metastatic breast cancer with 0–4 prior chemotherapy regimens . All received cyclophosphamide 50 mg daily , methotrexate 2.5 mg days 1–2 weekly , and v and etanib daily in 3 dose-escalation cohorts : 100 mg ( C1 ) , 200 mg ( C2 ) , and 300 mg ( C3 ) . The primary endpoint was safety and tolerability ; secondary endpoints included response rate and evaluation of platelet-associated proteins . Twenty three patients were treated and evaluable for toxicity . Common mild toxicities included nausea , vomiting , LFTs abnormalities , fatigue , and rash . Three episodes of dose-limiting toxicity occurred in C3 . In all cohorts , 1/3 of patients required v and etanib dose reduction , and 22 % ended therapy for toxicity . Of the 20 response-evaluable patients , 10 % demonstrated partial response and 15 % stable disease ≥24 weeks . Proteomic analyses demonstrated changes in platelet content of angiogenesis regulators , including vascular endothelial growth factor and platelet factor 4 , with exposure to therapy . This regimen was tolerable at a maximum v and etanib dose of 200 mg ; modest clinical activity was observed in this heavily pretreated population . Changes in the platelet proteome may serve as pharmacodynamic markers of angiogenesis inhibition . Metronomic chemotherapy is an attractive partner with biologics and deserves further study in metastatic breast cancer Background Metronomic oral vinorelbine could be a safe option for elderly patients with advanced non small cell lung cancer ( NSCLC ) . Metronomic administration of chemotherapy leads to a cytostatic action shifting treatment target from cancer cell to tumor angiogenesis . Methods 43 chemotherapy naive elderly ( ≥70 yrs ) PS 0 - 2 patients with stage IIIB-IV NSCLC were prospect ively recruited . Median age was 80 yrs ( M/F 36/7 ) with predominantly squamous histology . PS distribution was 0 - 1(16)/2(27 ) with a median of 3 serious co-morbid illnesses . Study treatment consisted of oral vinorelbine 50 mg three times weekly ( Monday-Wednesday-Friday ) continuously until disease progression , unacceptable toxicity or patient refusal . Primary endpoints were overall response rate ( ORR ) , clinical benefit ( CB – disease response plus disease stabilization > 12 weeks ) and safety . Health-related QoL ( HRQoL ) was also assessed with FACT-L V4 scoring question naire . We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 ( TSP1 ) serum levels in a subgroup of patients . Results Patients received a median of 5 ( range 1 - 21 ) cycles with a total of 272 cycles delivered . ORR was 18.6 % with 7 partial and 1 complete responses ; 17/43 experienced stable disease lasting more than 12 weeks leading to an overall CB of 58.1 % . Median time to progression was 5 ( range 2 - 21 ) and median overall survival 9 ( range 3 - 29 ) months . Treatment was well tolerated with rare serious toxicity . Regardless of severity main toxicities observed were anemia in 44 % , fatigue in 32.4 % , and diarrhoea 10.5 % . FACT-L v4 scores did not significantly vary during treatment . Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change . Conclusions Metronomic oral vinorelbine is safe in elderly patients with advanced NSCLC with an interesting activity mainly consisting in long-term disease stabilization coupled with an optimal patient compliance ( Eudra-CT 2010 - 018762 - 23 , AIFA OSS on 26 February 2010 ) Importance Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors , a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed . Skepticism abounds because of the lack of level 1 evidence . Objectives To compare the effect of metronomic chemotherapy on progression-free survival ( PFS ) with that of placebo in pediatric patients with primary extracranial , nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy . Design , Setting , and Participants A double-blinded , placebo-controlled r and omized clinical trial was conducted from October 1 , 2013 , through December 31 , 2015 , at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial , nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options . Interventions One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide , whereas the other arm received placebo . Disease status was assessed at baseline , 9 weeks , 18 weeks , and 27 weeks or at clinical progression . Main Outcomes and Measures The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months , and PFS duration and overall survival ( OS ) were secondary end points . Results A total of 108 of the 123 patients screened were enrolled , with 52 r and omized to the placebo group ( median age , 15 years ; 40 male [ 76.9 % ] ) and 56 to the metronomic chemotherapy group ( median age , 13 years ; 42 male [ 75.0 % ] ) . At a median follow-up of 2.9 months , 100 % of the patients had disease progression by 6 months in the placebo group vs 96.4 % in the metronomic chemotherapy group ( P = .24 ) . Median PFS and OS in the 2 groups was similar ( hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.47 - 1.03 [ P = .07 ] for PFS ; and HR , 0.74 ; 95 % CI , 0.50 - 1.09 [ P = .13 ] for OS ) . In post hoc subgroup analysis , cohorts receiving more than 3 cycles ( HR for PFS , 0.46 ; 95 % CI , 0.23 - 0.93 ; P = .03 ) and those without a bone sarcoma ( ie , neither primitive neuroectodermal tumor nor osteosarcoma ) ( HR for PFS , 0.39 ; 95 % CI , 0.18 - 0.81 ; P = .01 ) appeared to benefit from metronomic chemotherapy . Conclusions and Relevance Metronomic chemotherapy does not improve 6-month PFS , compared with placebo , among pediatric patients with extracranial progressive solid malignant tumors . However , patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles ( 9 weeks ) benefit . Trial Registration clinical trials.gov Identifier : NCT01858571 Prognosis of recurrent glioblastoma ( GBM ) is poor with 6-month progression-free survival ( PFS6 ) ranging from 9 to 48 % depending on the treatment regimen and use of anti-angiogenic therapies . We sought to study vorinostat ( VOR ) , a histone deacetylase inhibitor , in combination with bevacizumab ( BEV ) and daily metronomic temozolomide ( TMZ ) in a Phase I/II trial in recurrent high- grade gliomas ( HGGs ) . This was a Phase I/II open-label , single-arm study in recurrent HGG patients . Phase I primary endpoint was to determine the maximum tolerated dose ( MTD ) of VOR with BEV and daily TMZ . Phase II primary endpoint was PFS6 . Regimen was BEV 10 mg/kg iv every 2 weeks , TMZ 50 mg/m2 po daily , and VOR 200 or 400 mg po alternating 7 days on then 7 days off throughout a 28-day cycle . Phase I portion enrolled nine subjects with three receiving VOR 200 mg and 6 receiving VOR 400 mg . With no dose-limiting toxicities ( DLTs ) at 200 mg and one DLT ( thrombocytopenia , Grade 3 ) at 400 mg , the MTD was 400 mg . Phase II portion enrolled 39 GBM subjects , and PFS6 was 53.8 % ( 95 % CI 37.2–67.9 % ) . Of note , 14 subjects had received prior BEV and all had received prior 5-day TMZ . Combination therapy with VOR , BEV , and daily TMZ was well tolerated and safe . While PFS6 was not statistically improved beyond historical controls , it is important to note that this was a heavily pretreated GBM population and further consideration is warranted in a less pretreated group INTRODUCTION The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy , a novel anti-angiogenic treatment strategy , in combination with bevacizumab in patients with advanced non-small cell lung cancer ( NSCLC ) . METHODS Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80mg/m2 and gemcitabine 300mg/m2 weekly for three weeks , plus bevacizumab 10mg/kg every two weeks . Radiologic assessment s were performed every 8 weeks . The primary endpoint was progression free survival ( PFS ) . An exploratory objective was to correlate plasma levels of angiogenic biomarkers with treatment response . RESULTS Thirty-nine subjects were included in the intent to treat ( ITT ) analysis . The objective response rate ( ORR ) was 56 % , the median PFS was 8.5 months , and median overall survival ( OS ) was 25.5 months . The PFS rate at 6 , 12 , and 24 months was 61 % , 21 % , and 11 % respectively . The OS rate at 12 and 24 months was 74 % and 53 % respectively . Treatment was well tolerated , without significant myelosuppressive , gastrointestinal , or neurologic events . Subjects with less than median baseline values of angiopoietin-2 and IL-8 experienced significantly longer PFS . Longer OS was associated with subjects with less than the median baseline values for PLGF and angiopoietin-2 . There were statistically significant differences in median values of several biomarkers between cycles 1 and 3 in subjects with objective responses . CONCLUSIONS The combination of paclitaxel and gemcitabine , delivered in a metronomic schedule , in combination with bevacizumab , appears to be an effective and tolerable treatment strategy in patients with advanced NSCLC Abstract Background . Relapsed or refractory ( R/R ) classical Hodgkin lymphoma ( cHL ) after autologous stem cell transplantation ( ASCT ) remains a challenge . For these patients treatments with different mechanisms of action rather than classical chemotherapy are needed . Patients and methods . Patients with R/R cHL after ASCT were recruited in a phase II trial ( EUDRA CT : 2009 - 016588 - 12 ) . Lenalidomide was administered at 20 mg/day for 21 days and cyclophosphamide at 50 mg/day for 28 days ( cycles every 28 days ) . Dose escalation for lenalidomide was permitted . In 2009 we considered that this treatment would be promising if response rate were over 60 % and a Simon two-stage binomial design was used to calculate the sample size . A total of 46 patients were planned but the trial would be stopped if less than seven responses after four cycles were obtained in the first 16 patients . Results . The trial was closed early because only five responses were observed after four cycles in the first 16 patients included . Median age was 34 years ( 18–77 ) . The median number of previous lines was five ( 2–6 ) . At inclusion , 10 patients were primary refractory and 11 refractory to the last therapy . A total of 110 cycles were administered , with grade ≥ 3 toxicity in 43 cycles ( 39 % ) . One non-neutropenic patient developed septic shock result ing in death . An ORR of 38 % ( 1 CR and 5 PR ) was observed and a total of 10 patients ( 62 % ) achieved clinical benefit . Median progression free survival and overall survival were seven and 19 months , respectively . With a median follow-up of 19 months ( 3–38 + ) , three-year progression-free and overall survival were 6 % and 31 % , respectively . Conclusion . The optimistic assumptions of this trial led to an early closure . However , the promising clinical benefit observed with the oral combination of lenalidomide and metronomic cyclophosphamide may justify its use for outpatient palliative treatment Purpose The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients . The VICTOR-2 study was design ed to confirm these results . Methods Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day , continuously . The primary endpoint was the clinical benefit rate ( CBR ) ; secondary endpoints were toxicity , objective response rate ( ORR ) , and progression-free survival ( PFS ) . Results Eighty patients were evaluable for the primary efficacy analysis . Median age was 65.3 years ; most patients had HR-positive tumors ( 65 % ) . The CBR was 45.7 % ( 95 % CI 28.8–63.4 ) and 51.1 % ( 95 % CI 35.8–66.3 ) in first- and ≥ second-line therapy , respectively . The ORR was 35.5 % in first-line ( 95 % CI 19.2–54.6 ) and 25.6 % in ≥second-line ( 95 % CI 13.5–41.2 ) . The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 % , respectively . In triple-negative breast cancer patients ( N = 28 , 35 % ) a lower , but clinical ly relevant CBR ( 35.7 , 95 % CI 18.6–55.9 ) was observed . The main toxicities per cycle were non-febrile neutropenia ( 1.1 % ) , h and -foot syndrome ( 1.0 % ) , nausea and vomiting ( 1.0 % ) , leucopenia ( 0.8 % ) , fatigue ( 0.7 % ) , and diarrhea ( 0.4 % ) . Conclusion The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients , suggesting that the easy schedule of administration , which requires monthly blood tests and limits patients ’ dependence on hospitals , and the low cost of the drugs are valuable elements , even for countries with limited access to innovative or expensive drugs Background Adding bevacizumab to chemotherapy improves response rates and progression-free survival ( PFS ) in metastatic breast cancer ( mBC ) . We aim ed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab . Methods This multicenter , r and omized phase III trial compared bevacizumab with either paclitaxel ( arm A ) or daily oral capecitabine-cyclophosphamide ( arm B ) as first-line treatment in patients with HER2-negative advanced breast cancer . The primary endpoint was the incidence of selected grade 3–5 adverse events ( AE ) including : febrile neutropenia , infection , sensory/motor neuropathy , and mucositis . Secondary endpoints included objective response rate , disease control rate , PFS , overall survival ( OS ) , quality of life ( QoL ) , and pharmacoeconomics . The study was registered prospect ively with Clinical Trials.gov , number NCT01131195 on May 25 , 2010 . Results Between September 2010 and December 2012 , 147 patients were included at 22 centers . The incidence of primary endpoint-defining AEs was similar in arm A ( 25 % [ 18/71 ] ; 95 % CI 15–35 % ) and arm B ( 24 % [ 16/68 ] ; 95 % CI 13–34 % ; P = 0.96 ) . Objective response rates were 58 % ( 42/73 ; 95 % CI 0.46–0.69 ) and 50 % ( 37/74 ; 95 % CI 0.39–0.61 ) in arms A and B , respectively ( P = 0.45 ) . Median PFS was 10.3 months ( 95 % CI 8.7–11.3 ) in arm A and 8.5 months ( 95 % CI 6.5–11.9 ) in arm B ( P = 0.90 ) . Other secondary efficacy endpoints were not significantly different between study arms . The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent . Conclusion This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3–5 AEs with metronomic bevacizumab , cyclophosphamide and capecitabine Purpose This study aim ed to evaluate the safety , tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional ( CSV ) and metronomic ( MSV ) dosing schedules in patients with advanced non-small cell lung cancer ( NSCLC ) . Methods This was an open-label , multiple dose-escalation phase I study . An alternating 3 + 3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level . Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group ( N = 16 ) and at 100 mg/week in the MSV group ( N = 14 ) . Erlotinib was administered orally daily . Results The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group . Grade 3/4 toxicities included neutropenia ( N = 2 ; 13 % ) and hyponatremia ( N = 1 ; 6 % ) in the CSV group , and neutropenia ( N = 5 ; 36 % ) in the MSV group . Objective response was achieved in 38 % and 29 % in the CSV and MSV groups respectively . Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose . However , at steady-state , significantly higher Cmax , higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group . Significantly higher steady-state Cmin , Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group . Conclusions Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups . Trial Registration Clinical Trials.gov Metronomic , low dose chemotherapy may have anti-angiogenic effects and augment the effects of lenalidomide in MDS and CMML . We evaluated the clinical efficacy , tolerability and anti-angiogenic effects of melphalan 2 mg and lenalidomide 10 mg for 21 days/28 in CMML ( n=12 ) and higher risk MDS ( n=8 ) patients in a prospect i ve phase II study . The primary endpoint was overall response and secondary endpoints included survival , progression-free survival , toxicity and biomarkers of angiogenesis . The median age was 73 years , 55 % were pretreated and transfusion dependent . The overall response rate was 3(15 % ) of 19 evaluable patients but 25 % in CMML and 33 % in pCMML . Dose reductions and /or delays were common due to myelosuppression . Transient spikes in circulating endothelial cells that declined below baseline were seen in responders and patients with CMML , suggesting anti-angiogenic activity . In conclusion , lenalidomide and metronomic low dose melphalan demonstrate signals of clinical and possible anti-angiogenic activity in patients with pCMML that require future validation . This trial was registered at clinical trial.gov under # NCT00744536 INTRODUCTION Recently the combination of the mammalian target of rapamycin ( mTOR ) inhibitor everolimus and the aromatase inhibitor exemestane has been shown to double the progression-free survival rate in advanced breast cancer . However , the effect of the interrelated pathways of hypoxia-inducible factor-1α ( HIF-1α ) and mTOR signaling , both of which are associated with a more aggressive breast cancer phenotype and endocrine resistance , on response in the neoadjuvant setting is unknown . We , therefore , have investigated the influence of these pathways with the aim of better defining those patients most likely to benefit from an endocrine-based therapy associated with/without mTOR inhibitors . PATIENTS AND METHODS A total of 107 women with T2 - 4 N0 - 1 and estrogen receptor-positive breast cancer were r and omly assigned to 6 months of primary letrozole ( 2.5 mg/daily ) ( LET ) or LET plus oral " metronomic " cyclophosphamide ( 50mg/daily ) ( LET-CYC ) . Phospo-mTOR and HIF-1α were evaluated in tumor specimens collected before and after treatment using a tissue microarray format . RESULTS LET-based therapy induced a downregulation of phospho-mTOR and HIF-1α expression ( P = .0001 and P < .004 , respectively ) . The reduction of HIF-1α expression observed was positively correlated with phospho-mTOR reduction ( P < .03 ) ; however , no treatment interaction between the two proteins was detected . HIF-1α expression was significantly modulated by the treatment ( P < .004 ) with a reduction both in the LET arm ( 45 % , n = 36/80 ) ( P = .05 ) and LET-CYC arm ( 55 % , n = 44/80 ) ( P = .04 ) . HIF-1α reduction showed a relationship with clinical response confined in LET arm only ( P < .03 ) . CONCLUSIONS In this neoadjuvant population , LET was able to modulate the phospho-mTOR and HIF-1α pathways and may define a sub population of nonresponders who may be most likely to benefit from mTOR inhibitors AIM To determine the maximum tolerated dose of hypofractionated radiotherapy ( HFRT ) plus concurrent metronomic chemotherapy in patients with hormone-refractory prostate cancer ( HRPC ) . PATIENTS AND METHODS A Phase I clinical trial was performed with cohorts of three to six patients per group . Eligible patients had HRPC without distant metastases . The radiotherapy dose was escalated in a stepwise fashion as follows : 60 , 65 , and 70 Gy at levels 1 , 2 , and 3 , respectively ( 25 fractions : levels 1 - 2 , and 26 fractions : level 3 ) . RESULTS Nine patients were enrolled . The radiotherapy dose was escalated from 60 to 70 Gy without any dose-limiting toxicity . The most common grade 1/2 toxicities were hematuria , dysuria , diarrhea and rectal-perirectal pain . The overall objective response rate was 9/9 ( 100 % ) ( 95 % CI=66.4%-100 % ) . The median time-to-progression was 19 months . CONCLUSION In the challenging setting of HRPC , HFRT up to 70 Gy with concurrent metronomic chemotherapy was well-tolerated and yielded encouraging disease control Purpose To evaluate the safety and efficacy of metronomic vinorelbine in combination with cisplatin as first-line treatment in patients with advanced non-small cell lung cancer ( NSCLC ) . Patients and methods A total of 41 patients with inoperable stage IIIb or stage IV NSCLC ( 14 with adenocarcinomas , 19 with squamous cell carcinoma and eight with other types ) , PS = 0–2 , were treated with cisplatin ( 80 mg/m2 ) in combination with oral metronomic vinorelbine ( 60 mg total dose , every other day ) in cycles of 21 days . Results A total of 35 patients who received at least one cycle of chemotherapy were evaluable for toxicity and response . Partial response was achieved in 13 patients ( ORR 37.1 % ; CI 21.1–53.1 % ) and stable disease in 10 ( 28.6 % ) . After a median follow-up period of 26.2 months ( range 0.5–33.4 months ) , the median progression-free survival was 4.2 months and the median overall survival 12.0 months . The 1-year survival rate was 52.6 % . Myelosuppression was the main adverse event with grade 3 and 4 neutropenia occurring in five ( 14.3 % ) and six ( 17.1 % ) patients , respectively . Three of these patients presented with febrile neutropenia and there was one death due to sepsis . Non-hematologic toxicities were mild . Conclusion Cisplatin in combination with metronomic vinorelbine is an active , although myelotoxic , therapeutic option in the first-line setting for the treatment of patients with locally advanced and metastatic non-small cell lung cancer , which merits further evaluation in r and omized trials Background : This phase 1 clinical trial was conducted to determine the safety , maximum-tolerated dose ( MTD ) , and pharmacokinetics of imatinib , bevacizumab , and metronomic cyclophosphamide in patients with advanced colorectal cancer ( CRC ) . Methods : Patients with refractory stage IV CRC were treated with bevacizumab 5 mg kg−1 i.v . every 2 weeks ( fixed dose ) plus oral cyclophosphamide q.d . and imatinib q.d . or b.i.d . in 28-day cycles with 3 + 3 dose escalation . Response was assessed every two cycles . Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour , endothelial , and immune cell subsets were measured . Results : Thirty-five patients were enrolled . Maximum-tolerated doses were cyclophosphamide 50 mg q.d . , imatinib 400 mg q.d . , and bevacizumab 5 mg kg−1 i.v . every 2 weeks . Dose-limiting toxicities ( DLTs ) included nausea/vomiting , neutropaenia , hyponatraemia , fistula , and haematuria . The DLT window required expansion to 42 days ( 1.5 cycles ) to capture delayed toxicities . Imatinib exposure increased insignificantly after adding cyclophosphamide . Seven patients ( 20 % ) experienced stable disease for > 6 months . Circulating tumour , endothelial , or immune cells were not associated with progression-free survival . Conclusion : The combination of metronomic cyclophosphamide , imatinib , and bevacizumab is safe and tolerable without significant drug interactions . A subset of patients experienced prolonged stable disease independent of dose level Background Pre clinical models show that an antiangiogenic regimen at low-dose daily ( metronomic ) dosing may be effective against chemotherapy-resistant tumors . We undertook a prospect i ve , open-label , single-arm , multi-institutional phase II study to evaluate the efficacy of a “ 5-drug ” oral regimen in children with recurrent or progressive cancer . Procedure Patients ≤21 years old with recurrent or progressive tumors were eligible . Treatment consisted of continuous oral celecoxib , thalidomide , and fenofibrate , with alternating 21-day cycles of low-dose cyclophosphamide and etoposide . Primary endpoint was to assess , within eight disease strata , activity of the 5-drug regimen over 27 weeks . Blood and urine angiogenesis markers were assessed . Results One hundred one patients were enrolled ; 97 began treatment . Median age was 10 years ( range : 191 days–21 years ) ; 47 ( 49 % ) were female . Disease strata included high- grade glioma ( HGG , 21 patients ) , ependymoma ( 19 ) , low- grade glioma ( LGG , 12 ) , bone tumors ( 12 ) , medulloblastoma/primitive neuroectodermal tumor ( PNET , 8) , leukemia ( 4 ) , neuroblastoma ( 3 ) , and miscellaneous tumors ( 18 ) . Treatment was generally well tolerated ; most common toxicities were hematologic . Twenty-four ( 25 % ) patients completed 27 weeks therapy without progression , including HGG : 1 ( 5 % ) , ependymoma : 7 ( 37 % ) , LGG : 7 ( 58 % ) , medulloblastoma/PNET : 1 , neuroblastoma : 1 , and miscellaneous tumors : 7 ( 39 % ) . Best response was complete response ( one patient with medulloblastoma ) , partial response ( 12 ) , stable disease ( 36 ) , progressive disease ( 47 ) , and inevaluable ( 1 ) . Baseline serum thrombospondin levels were significantly higher in patients successfully completing therapy than in those who progressed ( P = 0.009 ) . Conclusion The 5-drug regimen was well tolerated . Clinical activity was demonstrated in some but not all tumor strata . Pediatric Blood Cancer 2014;61:636–642 . © 2013 The Authors Pediatric Blood & Cancer Published by Wiley Periodicals , Background : Pre clinical findings suggest that imatinib mesylate ( IM ) and metronomic cyclophosphamide ( MC ) combination provides synergistic antiangiogenic activity on both pericytes and endothelial cells . Methods : We have design ed a 3 + 3 dose-escalating phase I trial with a fixed dose of MC ( 50 mg two times daily ) plus IM ( 400 mg per day ; 300 and 400 mg two times daily ) . Enrolled patients had IM- and sutininib-refractory advanced gastrointestinal stromal tumours ( GIST ) ( n=17 ) , chordoma ( n=7 ) and mucosal melanoma ( n=2 ) . Dose-limiting toxicities were monitored for the first 6 weeks . Progression-free survival ( PFS ) and response assessment are based on RECIST 1.0 guidelines . Pharmacokinetics of IM were measured before and after exposure to MC . Results : No dose-limiting toxicity was observed . Fourteen patients of the exp and ed cohort received 400 mg two times daily of IM with MC . Apart from a case of possibly related acute leukaemia occurring after 4 years of treatment , we did not see unexpected toxicity . No drug – drug pharmacokinetic interaction was observed . There was no objective response . We have observed long-lasting stable disease in chordoma patients ( median PFS=10.2 months ; range , 4.2–18 + ) and short-term stable disease in heavily GIST pretreated patients ( median PFS=2.3 months ; range , 2.1–6.6 ) . Conclusion : This combination is feasible and may warrant further exploration in refractory GIST or chordoma patients BACKGROUND The present monocentric and prospect i ve phase 1 study evaluated the safety of a metronomic chemotherapy in refractory tumors . PATIENTS AND METHODS Patients with advanced solid cancer refractory to st and ard therapy received a combination of low-dose vinorelbine , cyclophosphamide and interferon-alpha . A dose escalation model with 3 levels was planned . The primary end-point was safety and tolerability , secondary end-points were treatment continuation rate at 4 months , progression-free survival ( PFS ) , overall survival ( OS ) , radiological assessment ( MRI ) of anti-angiogenic effect . RESULTS Thirty patients were enrolled . No dose-limiting toxicity was observed . All but two adverse events were toxicities of grade 1 - 2 . Treatment continuation rate at 4 months was 6.67 % ( 2 out of 30 patients ) . Median PFS and OS were 1.6 and 6.1 months . Exploratory MRI analyses related to anti-angiogenic effect did not show any relevant modification . CONCLUSION This combination of metronomic chemotherapy is well-tolerated and deserves to be deeply explored in refractory solid tumors BACKGROUND Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning . Since off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach , metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low-income countries . OBJECTIVE The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease . MATERIAL S AND METHODS This prospect i ve , single-center study evaluated the use of a metronomics protocol , consisting of a first cycle of weekly vincristine 1.5 mg/m2 ( days : 1 , 8 , 15 and 22 ) , daily cyclophosphamide 25 mg/m2 ( days : 1 - 21 ) , twice weekly methotrexate 15 mg/m² ( days : 21 - 42 ) and daily valproic acid ( 30 mg/kg/d ) followed by a 1-week break . For the following cycles , vincristine was administrated only at week 1 and 5 of the cycle . This treatment was proposed to children with refractory disease and patients who were not eligible for the protocol s available in the hospital . Adverse events were determined through laboratory analyses and investigator observations . RESULTS From January 2010 to January 2011 , 7 children ( mean age : 5.4 ± 3 years old ) were treated . Most frequent diagnosis was retinoblastoma . Two partial responses were observed in patients with neuroblastoma and retinoblastoma . These two patients are alive with stable disease at last follow-up ( 6 and 26 months , respectively ) after stopping treatment . CONCLUSION Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low-income countries . The potential of metronomics in children and young adults living in middle- and low-income countries warrants further larger studies Purpose To determine the maximum tolerated dose ( MTD ) , toxicities , and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population . Material s and Methods Patients who were 1 to 30 years of age with relapsed/refractory solid tumors ( including CNS ) were eligible . Patients received daily oral sirolimus and cyclophosphamide ( 25 - 50 mg/m2/dose ) on days 1 - 21 and oral topotecan ( 0.8 mg/m2/dose ) on days 1 - 14 in 28-day cycles . Sirolimus steady-state plasma trough concentrations of 3 - 7.9 ng/mL and 8 - 12.0 ng/mL were evaluated , with dose escalation based on a 3 + 3 phase 1 design . Biomarkers of angiogenesis were also evaluated . Results Twenty-one patients were treated ( median age 18 years ; range 9 - 30 ) . Dose-limiting toxicities included myelosuppression , ALT elevation , stomatitis , and hypertriglyceridemia . The MTD was sirolimus with trough goal of 8 - 12.0 ng/mL ; cyclophosphamide 25 mg/m2/dose ; and topotecan 0.8 mg/m2/dose . No objective responses were observed . Four patients had prolonged stable disease > 4 cycles ( range 4 - 12 ) . Correlative biomarker analyses demonstrated reductions in thrombospondin-1 ( p=0.043 ) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline . Conclusions The combination of oral sirolimus , topotecan , and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen Introduction Using mathematical modelling allows to select a treatment 's regimen across infinite possibilities . Here , we report the phase I assessment of a new schedule for metronomic vinorelbine in treating refractory advanced NSCLC and mesothelioma patients . Results Overall , 13 patients were screened and 12 were treated ( 50 % male , median age : 68yrs ) , including 9 NSCLC patients . All patients received at least one week ( 3 doses ) of treatment . At data cut-off , the median length of treatment was 6.5 weeks ( 1–32 + ) . All the patients presented with at least one adverse event ( AE ) and six patients with a severe AE ( SAE ) . One partial response and 5 stable diseases were observed . The median OS was 6.4 months ( 95 % CI , 4.8 to 12 months ) . The median and mean vinorelbine 's AUC were 122 ng/ml*h and 159 ng/ml*h , respectively , with the higher plasmatic vinorelbine exposure associated with the best ORR ( difference of AUC comparison between responders and non-responders , p-value 0.017 ) . Material s and Methods The mathematical modelling determined the administration of vinorelbine , 60 mg on Day 1 , 30 mg on Day 2 and 60 mg on Day 4 weekly until progression , as the best schedule . Advanced NSCLC or mesothelioma patients progressing after st and ard treatment were eligible for the trial . NCT02555007 . Conclusions Responses with acceptable safety profile were observed in heavily pretreated NSCLC and mesothelioma patients using oral vinorelbine at this metronomic dosage based on a mathematic modeling . This study demonstrates the feasibility of this new type of approach , as mathematical modeling may help to rationally decide the better regimen to be clinical ly tested across infinite possibilities Studies have shown that cancer requires two conditions for tumor progression : cancer cell proliferation and an environment permissive to and conditioned by malignancy . Chemotherapy aims to control the number and proliferation of cancer cells , but it does not effectively control the two best-known conditions of the tumor-permissive environment : neoangiogenesis and tolerogenic immunity . Many malignant diseases exhibit poor outcomes after treatment with chemotherapy . Therefore , we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease . In a prospect i ve , r and omized trial , we included patients with advanced , unresectable pancreatic adenocarcinomas , non-small cell lung cancer , or prostate cancer . Two groups of each primary condition were compared : group 1 ( G1 ) , n = 30 , was treated with the st and ard chemotherapy and used as a control , and group 2 ( G2 ) , n = 30 , was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity . This induction regimen included a low dose of metronomic cyclophosphamide , a high dose of Cox-2 inhibitor , granulocyte colony-stimulating factor , a sulfhydryl ( SH ) donor , and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood . After treatment , the G2 group demonstrated significantly longer survival , lower blood level of neoangiogenesis and immune-tolerance mediators , and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group . Toxicity and quality of life were not significantly different between the groups . In conclusion , in several advanced malignancies of different primary localizations , an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to st and ard chemotherapy Background The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects . Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective . Methods This phase I study was performed using metronomic temozolomide ( mTMZ ) at 25 or 50 mg/m2/day continuously in 42-day cycles . Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow , analysis of matrix metalloproteinase-2 ( MMP-2 ) and MMP-9 activities in the cerebrospinal fluid ( CSF ) as surrogates for tumor angiogenesis and invasion , as well as determination of CSF soluble interleukin-2 receptor alpha ( sIL-2Rα ) levels as a marker of immune modulation . Results Nine subjects were enrolled and toxicity consisted of primarily grade 1 or 2 hematological and gastrointestinal side effects ; only one patient had a grade 3 elevated liver enzyme level that was reversible . Tumor blood flow was variable across subjects and time , with two experiencing a transient increase before a decrease to below baseline level while one exhibited a gradual drop in blood flow over time . MMP-2 activity correlated with overall survival but not with progression free survival , while MMP-9 activity did not correlate with either outcome parameters . Baseline CSF sIL-2Rα level was inversely correlated with time from initial diagnosis to first progression , suggesting that subjects with higher sIL-2Rα may have more aggressive disease . But they lived longer when treated with mTMZ , probably due to drug-related changes in T-cell constituency . Conclusions mTMZ possesses efficacy against recurrent malignant gliomas by altering blood flow , slowing invasion and modulating antitumor immune function Abstract The aim of the study was to retrospectively assess the efficacy and safety of low-dose metronomic oral capecitabine in pretreated or frail patients with recurrent colorectal cancer . Patients with recurrent colorectal cancer and prior treatment with fluoropyrimidines , oxaliplatin , and irinotecan or unable to receive st and ard chemotherapy because of toxicity concerns were included . Treatment consisted of oral capecitabine 1,500 mg daily until disease progression or unacceptable toxicity . Response rates were determined according to RECIST criteria . The end points were disease control rate [ ( DCR ) consisting of complete response , partial response ( PR ) , and stable disease ( SD ) ] , overall survival ( OS ) , and safety . Sixty-eight patients , median age 72.5 years , were treated . The median number of previous treatments was 2 ( range 0–5 ) . Sixty-two percent of patients had received ≥2 previous lines of treatment . The overall DCR was 26 % , PR in 2 ( 3 % ) and SD in 14 ( 23 % ) . Nineteen percent of patients were progression free for at least 6 months . In an exploratory analysis , there was a significant relation of performance status with DCR ( HR = 3.3 ; P = 0.05 ) . The median OS was 8 months . DCR was associated with a longer survival ( HR = 0.4 ; P < 0.01 ) . Grade 3 toxicities included anemia ( 1 ) , diarrhea ( 1 ) , and h and -foot syndrome ( 1 ) . There were no cases of grade 4 toxicity or treatment-related deaths . Metronomic capecitabine was moderately active and well-tolerated in pretreated or frail patients with recurrent colorectal cancer Background Elderly patients with metastatic breast cancer ( MBC ) have more problems receiving chemotherapy than younger patients , especially with the presence of multiple comorbidities , adverse drug events and functional decline . Low-dose oral administration of cytotoxic agents such as vinorelbine , a semisynthetic vinca alkaloid that interferes with microtubule assembly , leading to arrest of cell division , is usually effective and well tolerated . Methods From February 2010 to February 2014 , 32 patients with MBC , median age 76 years ( range 69 - 83 ) were treated with oral vinorelbine 30 mg ( total dose ) , one day on and one day off , until disease progression or unacceptable toxicity levels were reported . Toxicity , quality of life and clinical benefit were evaluated . Matched t-tests were conducted to discern whether quality -of-life indicator ( p<0.05 was considered significant ) differed before and 6 months after treatment . Statistical analysis was performed using Graph Pad Prism 5.0 ( GraphPad Software Inc. , San Diego , CA , USA ) . Results No grade 3 and 4 adverse events were reported . A clinical benefit of 50 % was found in our cohort . On and off metronomic vinorelbine oral administration result ed in good tolerability and safe profile in our selected elderly population , and improved patient adherence to therapy . Conclusions The present study demonstrated that metronomic vinorelbine might be a potential treatment in elderly patients by reducing adverse effects and increasing quality of life , setting the stage for future extensive clinical trials The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells . In addition , it has been reported to drive proliferation and promote invasion and metastasis . Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs . Moreover , early clinical data have supported the role of proton pump inhibitors in anticancer treatments . Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer . The present study ( EudraCT Number : 2013 - 001096 - 20 ) was aim ed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to st and ard treatment . A total of 66 patients will be r and omized 1:1 to receive capecitabine 1500 mg/daily , continuously with or without rabeprazole 1.5 mg/kg twice a day , 3 days a week until disease progression , undue toxicity , or withdrawal of informed consent . The primary endpoint is progression-free survival . The secondary endpoints are clinical benefit , which reflects the proportion of patients with complete response , partial response , and stable disease , and overall survival . Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05 . Other assessment s will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety , and the pharmacokinetics of capecitabine . The results are expected in 2016 Systemic therapy for advanced hepatocellular carcinoma ( HCC ) is still challenging . A biomodulatory therapy approach targeting the communicative infrastructure of HCC , including metronomic low-dose chemotherapy with capecitabine , pioglitazone and rofecoxib , has been evaluated in patients with non-curative HCC . Altogether 38 patients were evaluable in this one-arm , multicenter phase II trial . The primary endpoint , median progression-free survival was 2.7 months ( 95 % CI : 1.6–3.79 ) for all evaluable patients and 8.4 months ( 95 % CI : 0–18.13 ) for patients ≥ 6 weeks on protocol . Median overall survival ( OS ) was 6.7 months ( 95 % CI : 4.08–9.31 ) and 9.4 months ( 95 % CI : 4.82–13.97 ) , respectively . Most common adverse events were edemas grade 3 , which were commonly related to the advanced stage , with 66 % of the patients suffering from liver cirrhosis . Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS , 9.8 months ( 95 % CI : 4.24–15.35 ) versus 2.7 months ( 95 % CI : 1.03–4.36 ; P = 0.002 ) , and 9.8 months ( 95 % CI : 3.23–16.37 ) versus 4.4 months ( 95 % CI : 3.14–5.66 ; P = 0.009 ) , respectively . Preceding tumor surgery had significant beneficial impact on survival , as well as maximal tumor diameter of < 5 cm . The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control . Biomodulatory therapy in advanced HCC may be a low toxic , efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC Summary Background In tumors carrying BRCA mutations , DNA damage caused by st and ard cytotoxic chemotherapy can be potentiated by poly [ ADP-ribose ] polymerase ( PARP ) inhibitors , leading to increased cell death through synthetic lethality . Individuals carrying mutations in BRCA have an increased incidence of triple negative breast cancer ( TNBC ) . In order to assess the role of PARP inhibition in the treatment of TNBC , we conducted a r and omized phase II trial of the combination of veliparib , a small molecule PARP inhibitor , with the cytotoxic agent cyclophosphamide versus cyclophosphamide alone in patients with refractory TNBC . Methods Adult patients with TNBC were r and omized to receive oral cyclophosphamide 50 mg once daily with or without oral veliparib at 60 mg daily in 21-day cycles . Patients on the cyclophosphamide arm could crossover to the combination arm at disease progression . Results Forty-five patients were enrolled ; 18 received cyclophosphamide alone and 21 received the combination as their initial treatment regimen . Lymphopenia was the most common grade 3/4 toxicity noted in both arms . One patient in the cyclophosphamide alone arm , and 2 in the combination arm had objective responses . Response rates and median progression free survival did not significantly differ between both treatment arms . Conclusion The addition of veliparib to cyclophosphamide , at the dose and schedule evaluated , did not improve the response rate over cyclophosphamide treatment alone in patients with heavily pre-treated triple-negative breast cancer PURPOSE The aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by st and ard adjuvant chemotherapy in triple-negative breast cancer ( TNBC ) patients . METHODS Between June 2010 and February 2012 , 19 women with pathologically proven operable TNBC , who had received st and ard adjuvant chemotherapy before were enrolled . Patients received 1 year of oral capecitabine metronomic therapy ( 650 mg/m2 , twice every day ) , after st and ard adjuvant chemotherapy and radiotherapy if indicated . The primary endpoints of this study were disease-free survival rates ( DFS ) and safety profile . Secondary end point was overall survival ( OS ) . RESULTS The maximal follow-up was 46.6 months with a median of 30.1 months±11.525 ( 95 % CI ; 28.5 - 33.5 months ) . The median DFS was 41.7 months±2.7 ( 95 % CI ; 36.5 - 46.9 ) . No one developed locoregional recurrence . The actuarial rate of DFS was 88.8 % and 82.05 % at 2 and 3 years , respectively . At the time of the analyses , no patients had died and the median OS was not reached . Treatment-related adverse events were manageable with only 1 patient ( 5.3 % ) suffering from Grade 3/4 h and -foot syndrome and another 1 patient ( 5.3 % ) suffering from Grade 3 diarrhea . No Grade 3/4 hematologic toxicity was recorded . All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients . CONCLUSION One year of capecitabine metronomic therapy preceded by st and ard adjuvant chemotherapy , is active and well-tolerated in TNBC patients previously treated with st and ard adjuvant chemotherapy Purpose Better treatments for triple-negative breast cancer ( TNBC ) are needed . To address this need , we studied the effects of preoperative metronomic paclitaxel/cyclophosphamide/capecitabine ( mPCX ) followed by 5-fluorouracil (FU)/epirubicin/cyclophosphamide ( FEC ) as preoperative chemotherapy in TNBC patients . Methods Forty primary TNBC patients received four cycles of metronomic paclitaxel ( 80 mg/m2 on Days 1 , 8 , and 15 ) , cyclophosphamide ( 50 mg/body daily ) , and capecitabine ( 1,200 mg/m2 daily ) , followed by four cycles of 5-FU ( 500 mg/m2 ) , epirubicin ( 100 mg/m2 ) , and cyclophosphamide ( 500 mg/m2 ) every 3 weeks . The primary end point was the pathological complete response ( pCR ) rate . Results Forty patients formed the intent-to-treat population . The median dose intensities of paclitaxel , cyclophosphamide , and capecitabine were 89.7 , 92.1 , and 89.8 % , respectively . Five patients discontinued mPCX and two discontinued FEC , primarily because of adverse events , result ing in a per- protocol population ( PPS ) of 33 patients . The pCR ( ypT0/Tis ypN0 ) rate was 47.5 % ( 19/40 ) in the intent-to-treat population and 54.5 % ( 18/33 ) in the PPS . The clinical response rates were 36/40 ( 90.0 % ) and 31/33 ( 93.9 % ) in the intent-to-treat and PPS , respectively . The breast conservation rate was 72.7 % ( 24/33 ) , and 5/13 patients underwent partial resection instead of pre-planned total mastectomy . Grade 3–4 adverse events included neutropenia ( 35 % ) , leukopenia ( 25 % ) , and h and -foot syndrome ( 8 % ) . Conclusions Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients . Further studies of this regimen in larger numbers of patients are warranted BACKGROUND Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme ( GBM ) . Pre- clinical and clinical investigations also showed that continuous low-dose temozolomide has some antiangiogenic activity . Based on this evidence , a phase II trial was design ed to investigate an oral regimen of sorafenib , an oral multikinase inhibitor , and metronomic temozolomide for relapsed GBM . PATIENTS AND METHODS Forty-three patients ( median age=60.0 years ) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression . RESULTS Toxicity , mostly grade 1 - 2 , was manageable . Grade 3 - 4 toxicities were h and -foot syndrome ( n=4 ) , hypertension ( n=2 ) , and fatigue ( n=3 ) . Five patients ( 12 % ) achieved partial response , 18 ( 43 % ) stable disease , 20 ( 48 % ) showed progression . The median time-to-progression was 3.2 months , 6-month progression-free survival was 26 % , and median overall survival was 7.4 months . CONCLUSION This combination of sorafenib and temozolomide was feasible and safe , showing some activity in patients with relapsed GBM Metronomic chemotherapy ( MCT ) , the chronic administration , at regular intervals , of low doses of chemotherapeutic drugs without extended rest periods , allows chronic treatment with therapeutic efficacy and low toxicity . Our pre clinical results suggested that combined MCT with cyclophosphamide and celecoxib could inhibit breast cancer growth . The aim of this study was to determine the toxicity , safety and efficacy of oral MCT with cyclophosphamide 50 mg per orem daily and celecoxib 400 mg ( 200 mg per orem two-times a day ) in advanced breast cancer patients . During the first stage of the study , the therapeutic response consisted of prolonged stable disease for ≥24 weeks in six out of 15 ( 40 % ) patients with a median duration of 37.5 weeks and a partial response in one out of 15 ( response rate : 6.7 % ) patients lasting 6 weeks . The overall clinical benefit rate was 46.7 % . The median time to progression was 14 weeks . Progression-free survival at 24 weeks was 40 % and the 1-year overall survival rate was 46.7 % . The adverse events were mild ( gastric , grade 1 ; and hematologic , grade 1 or 2 ) . No grade 3 or 4 toxicities were associated with the treatment . Evaluation of patients ' quality of life showed no changes during the response period . MCT with cyclophosphamide plus celecoxib is safe and shows a therapeutic effect in advanced breast cancer patients Newly diagnosed glioblastoma multiforme with unmethylated MGMT promoter has a poor prognosis , with a median survival of 12 months . This phase II study investigated the efficacy and safety of combining the selective integrin inhibitor cilengitide with a combination of metronomic temozolomide and procarbazine for these patients . Eligible patients ( newly diagnosed , histologically confirmed supratentorial glioblastoma with unmethylated MGMT promoter ) were entered into this multicentre study . Cilengitide ( 2000 mg IV twice weekly ) was commenced 1 week prior to radiotherapy combined with daily temozolomide ( 60 mg/m2 ) and procarbazine ( 50 or 100 mg ) and , after 4 weeks ’ break , followed by six adjuvant cycles of temozolomide ( 50–60 mg/m2 ) and procarbazine ( 50 or 100 mg ) on days 1–20 , every 28 days . Cilengitide was continued for up to 12 months or until disease progression or unacceptable toxicity . The primary endpoint for efficacy was a 12-month overall survival rate of 65 % . Twenty-nine patients completed study treatment . Sixteen patients survived for 12 months or more , an overall survival rate of 55 % . The median overall survival was 14.5 months ( 95 % CI 11.1–19.6 ) and the median progression-free survival was 7.4 months ( 95 % CI 6.1–8 ) . Cilengitide combined with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated glioblastoma did not improve survival compared with historical data and does not warrant further investigation Summary The aim of the present study was to evaluate clinical activity , and the pharmacodynamic and pharmacokinetic profiles , of oral metronomic vinorelbine ( VNR ) plus dexamethasone ( DEX ) in metastatic castration-resistant prostate cancer ( mCRPC ) patients . Fourty-one patients ( 92 % chemotherapy-resistant ) received 30 mg/day VNR p.o . thrice a week plus 1 mg/day DEX p.o . until disease progression . Plasma soluble B cell antigen 7 homolog 3 ( sB7-H3 ) , vascular endothelial growth factor ( VEGF ) , and thrombospondin-1 ( TSP-1 ) , were measured by ELISA . Plasma VNR was detected using a LC-MS-MS system . The fraction of patients free of progression , defined by criteria of the Prostate Cancer Clinical Trials Working Group 2 , at 3 months was 61 % . PSA decrease ≥50 % from baseline was observed in 35 % of patients . Median PFS and OS were 4 months ( 95 % CI , 2.8–6.9 ) and 17.5 months ( 95 % CI , 10.8–24.5 ) , respectively . Toxicity was mild , and no grade 4 toxicities were found . The mean plasma VNR Cmax ranged from 1 to 2.7 ng/ml ( Tmax 1.1 h ) and no evidence of drug accumulation was found . A moderate relationship was found between plasma sB7-H3 and PSA values ( r = 0.565 ; P = 0.0094 ) at the baseline . Increased PFS ( 11.3 vs. 2.8 months ; P = 0.0298 ) was observed in patients with sB7-H3 levels < 30.25 ng/mL. Plasma VEGF AUC0 - 24day increased in non-responders ( P < 0.0001 ) , whereas responders maintained higher plasma TSP-1 AUC0 - 24day ( P = 0.0063 ) . In conclusion , metronomic VNR plus DEX showed favourable activity , and a low toxicity profile , in mCRPC patients . Plasma sB7-H3 , VEGF and TSP-1 levels are potential pharmacodynamic markers at the reached low plasma concentrations of vinorelbine metronomically administered PURPOSE The prognosis is poor for patients with recurrent , platinum-resistant epithelial ovarian cancer ( EOC ) . Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC . A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent , previously treated EOC . PATIENTS AND METHODS This study was design ed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent , platinum-resistant , previously treated ovarian , peritoneal , or fallopian tube cancer . Here , 50 mg cyclophosphamide were combined with 400 to 800 mg pazopanib daily . RESULTS Sixteen patients were treated ; mean age was 66years . At dose levels ( DL ) I and II , one instance of dose-limiting toxicity ( DLT ) was seen in one of 6 patients . At DL III , two of four patients showed a DLT , leading to a maximum tolerated dose ( MTD ) of 600 mg pazopanib daily . Median number of administered cycles was 6 ( 2 - 13 ) , with three patients being treated for at least 13months . Median progression-free survival ( PFS ) and overall survival ( OS ) were 8.35months and 24.95months , respectively . 155 adverse events ( AE ) occurred , most frequently elevation of liver enzymes , leukopenia , diarrhea and fatigue . Altogether , five serious adverse events ( SAE ) developed in four patients . CONCLUSION Pazopanib 600 mg daily p.o . and metronomic cyclophosphamide 50 mg daily p.o . is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population . TRIAL REGISTRATION Clin.trial.gov registry no. : NCT01238770 OBJECT Locoregional chemotherapy with carmustine wafers , positioned at surgery and followed by radiation therapy , has been shown to prolong survival in patients with newly diagnosed glioblastoma , as has concomitant radiochemotherapy with temozolomide . A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies . METHODS In a single-institution prospect i ve study , the authors assessed 12-month progression-free survival ( PFS ) , toxicity , and overall survival in patients with glioblastoma treated with surgery , carmustine wafers , radiotherapy , and 6-month metronomic temozolomide chemotherapy . Thirty-five patients with de novo glioblastoma , between the ages of 18 and 70 years , and with Karnofsky Performance Scale scores of at least 70 , were included in the study . Patients were followed monthly and assessed using MRI every 2 months . RESULTS After a median follow-up of 15 months , the median time to tumor progression was 12.5 months and median survival was 17.8 months . Due to toxicity ( mostly hematological ) , 7 patients had to prematurely stop temozolomide treatment . Twenty-two patients developed Grade 3 CD4(+ ) lymphocytopenia . Three patients developed oral-esophageal c and idiasis , 2 developed pneumonia , and 1 developed a dorsolumbar zoster . Early intracranial hypertension was observed in 1 patient , and 1 was treated empirically for suspected brain abscess . One patient died of Legionella pneumonia soon after repeat surgery . CONCLUSIONS Overall , this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen . However , the gain in median survival using this schedule was less clear . Only prospect i ve comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile BACKGROUND / AIM The optimal therapeutic use of metronomic vinorelbine has not yet been defined . We aim ed to assess the safety of metronomic oral vinorelbine in first-line treatment of elderly patients with advanced lung cancer who were unfit for polychemotherapy . Progression-free survival , response rate and overall survival were secondary end-points . PATIENTS AND METHODS Seventy-six patients received 50 mg of oral vinorelbine three times per week , until disease progression , patient refusal or unacceptable toxicity . Patients were evaluated for response and toxicity after one cycle of chemotherapy . The treatment was considered feasible with a grade 3/4 toxicity rate lower than 20 % . RESULTS Clinical benefit was observed in 50 % of patients . Median overall survival was 8.0 months . Grade 1/2 toxicity was observed in 53 patients ( 69.7 % ) , grade 3 toxicity in eight patients ( 10.5 % ) . One patient had grade 4 diarrhea . CONCLUSION Metronomic oral vinorelbine is safe in elderly patients , allowing for long-term disease stabilization with optimal patient compliance PURPOSE High interest in triple-negative breast cancers is not surprising as this category of patients benefits neither from hormonal therapies nor from anti HER2 treatments . Blockade of angiogenesis by metronomic chemotherapy as well as other antiangiogenics might improve outcomes in this group of patients . This study aims to evaluate the tolerability and efficacy of metronomic capecitabine as extended adjuvant treatment for women with triple-negative breast cancer . METHODS This is a prospect i ve phase II study that included 41 patients diagnosed with triple-negative breast cancer and who were indicated for adjuvant chemotherapy . They received capecitabine 500 mg PO twice daily and continuously for six months after finishing six cycles of adjuvant FEC100±postoperative radiotherapy . RESULTS Forty-one patients were enrolled in this study between June 2010 and December 2013 . Median age was 50years ranging from 27 to 67years . Treatment was well tolerated . Adverse effects were grade 1 palmar-plantar erythrodysesthesia in 13 patients ( 31.7 % ) ; grade 1 diarrhea in five patients ( 12.2 % ) ; and grade 1 vomiting in two patients ( 4.9 % ) . Estimated median follow-up duration was 34 months . Estimated mean disease-free survival ( DFS ) was 42.4months ( 95 % CI , 39.02 - 45.79 ) , while median DFS was not reached . Estimated mean overall survival was 44.34months ( 95 % CI 41.9 - 46.9 ) . CONCLUSION Extended adjuvant metronomic capecitabine is well tolerated with patient compliance . These results need to be compared in a study with control arm , larger sample , as well as longer follow-up Abstract Purpose : Anti-angiogenic agents have shown promise for treating advanced hepatocellular carcinoma ( HCC ) , and the primary mechanism of low-dose metronomic chemotherapy using traditional cytotoxic drugs is anti-angiogenic . This study evaluated the efficacy of metronomic capecitabine and thalidomide after cool-tip radiofrequency ablation ( RFA ) , relative to RFA alone , for treating patients with HCC . Methods and material s : Patients with HCC were r and omly apportioned to a test group ( n = 22 ) receiving metronomic chemotherapy with capecitabine and thalidomide after RFA , or a control group ( n = 28 ) receiving RFA only . Serum circulating endothelial cells ( CECs ) and vascular endothelial growth factor ( VEGF ) were measured in all patients before and 1 month after RFA treatment . Enhanced computed tomography or ultrasound imaging was performed to evaluate efficacy during 12 months of follow-up . The treatment groups were further stratified as HCC within or outside the Milan criteria for transplantation . Results : One month post-treatment , the tumour response rate ( TRR ) , including complete response and partial response rate , of the test and control groups was statistically similar . At 12 months , the TRR of the test group ( 68.2 % ) was significantly higher than that of the control group ( 35.7 % ) . In the test group , the TRR of patients whose tumour burdens were outside the Milan criteria was significantly higher than that of the control group . One month post-treatment , CECs and VEGF levels of the test group were significantly lower than baseline , while those of the control group were significantly higher . At the end of the 12-month follow-up , there was a progression-free survival ( PFS ) benefit of 2 months in the test group . Conclusion : Metronomic capecitabine and thalidomide after RFA significantly reduced recurrence of HCC and extended PFS , especially for HCC outside the Milan criteria , perhaps via reduction of serum CECs and VEGF levels and inhibition of tumour angiogenesis PURPOSE This multicenter , r and omized , open-label , phase III trial compared the efficacy and safety of decitabine with treatment choice ( TC ) in older patients with newly diagnosed acute myeloid leukemia ( AML ) and poor- or intermediate-risk cytogenetics . PATIENTS AND METHODS Patients ( N = 485 ) age ≥ 65 years were r and omly assigned 1:1 to receive decitabine 20 mg/m(2 ) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC ( supportive care or cytarabine 20 mg/m(2 ) per day as a subcutaneous injection for 10 consecutive days every 4 weeks ) . The primary end point was overall survival ( OS ) ; the secondary end point was the complete remission ( CR ) rate plus the CR rate without platelet recovery ( CRp ) . Adverse events ( AEs ) were recorded . RESULTS The primary analysis with 396 deaths ( 81.6 % ) showed a nonsignificant increase in median OS with decitabine ( 7.7 months ; 95 % CI , 6.2 to 9.2 ) versus TC ( 5.0 months ; 95 % CI , 4.3 to 6.3 ; P = .108 ; hazard ratio [ HR ] , 0.85 ; 95 % CI , 0.69 to 1.04 ) . An unplanned analysis with 446 deaths ( 92 % ) indicated the same median OS ( HR , 0.82 ; 95 % CI , 0.68 to 0.99 ; nominal P = .037 ) . The CR rate plus CRp was 17.8 % with decitabine versus 7.8 % with TC ( odds ratio , 2.5 ; 95 % CI , 1.4 to 4.8 ; P = .001 ) . AEs were similar for decitabine and cytarabine , although patients received a median of four cycles of decitabine versus two cycles of TC . The most common drug-related AEs with decitabine were thrombocytopenia ( 27 % ) and neutropenia ( 24 % ) . CONCLUSION In older patients with AML , decitabine improved response rates compared with st and ard therapies without major differences in safety . An unplanned survival analysis showed a benefit for decitabine , which was not observed at the time of the primary analysis UNLABELLED Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma ( HCC ) . This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC . METHODS This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib . The treatment schedule was capecitabine 500 mg twice daily until progression of disease , unacceptable toxicity level , or withdrawal of informed consent . Progression-free survival ( PFS ) was chosen as the primary endpoint . RESULTS A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled . The first cohort achieved a median PFS of 6.03 months and an overall survival ( OS ) of 14.47 months . Two patients achieved a complete response , 1 patient achieved partial response , and in 30 patients , stable disease was the best outcome . The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months . No complete or partial responses were observed , but 10 patients had stable disease . An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer ( ITA.LI.CA ) data base was performed . One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients . The median OS for these 50 capecitabine-treated patients was 15.6 months , compared with a median OS of 8.0 months for the matched untreated patients ( p = .043 ) . CONCLUSION Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib The average survival time for patients with recurrent glioblastoma is between 5 and 9 months . Phase I and II trials have shown a modest survival benefit with combination temozolomide and other chemotherapeutics . We conducted a phase I trial of dose-escalating temozolomide with bevacizumab and the proteasome inhibitor bortezomib for patients with recurrent disease . Three groups of three patients were scheduled to receive daily doses of temozolomide at 25 , 50 , and 75 mg/m2 . Fixed doses of bortezomib and bevacizumab were given at st and ard intervals . Patients were monitored for dose-limiting toxicities ( DLT ) to determine the maximum-tolerated dose ( MTD ) of temozolomide with this regimen . No DLT were seen in the first two groups ( 25 and 50 mg/m2 temozolomide ) . One patient in the 75 mg/m2 group experienced a grade 4 elevation of ALT and three more patients were accrued for a total of six patients at that dose level . No other DLT occurred , thus making 75 mg/m2 the MTD . Progression-free survival was 3.27 months for all patients and mean overall survival was 20.75 months . The MTD of temozolomide was 75 mg/m2 in combination with bevacizumab and bortezomib for recurrent glioblastoma . Only one patient experienced a severe ( Grade 4 ) elevation of ALT . This study will provide the framework for further studies to elicit effectiveness and better determine a safety profile for this drug combination This phase II study was conducted to determine the efficacy and safety of metronomic temozolomide ( TMZ ) in combination with irinotecan in glioblastoma ( GB ) at first relapse . Patients with GB at first relapse received TMZ 50 mg/m2/day divided into three doses , except for a single 100 mg/m2 dose , administered between 3 and 6 h before every irinotecan infusion . Irinotecan was given intravenously at the previously established dose of 100 mg/m2 on days 8 and 22 of 28-day cycles . Treatment was given for a maximum of nine cycles or until progression or unacceptable toxicity occurred . Vascular endothelial growth factor and its soluble receptor 1 , thrombospondin-1 , microparticles , and microparticle-dependent procoagulant activity were measured in blood before treatment . The primary objective was 6-month progression-free survival ( PFS ) . Twenty-seven evaluable patients were enrolled . Six-month PFS was 20.8 % . Median PFS was 11.6 weeks ( 95 % confidence interval : 7.5–15.7 ) . Stable disease was the best response for nine ( 37.5 % ) patients , with a median duration of 11.2 weeks ( 4.2–35.85 weeks ) . No differences in PFS or response were observed among patients who relapsed during or after completion of adjuvant TMZ . Grade 3/4 adverse events included lymphopenia ( 15 % ) , fatigue , diarrhea and febrile neutropenia ( 3.7 % each ) , lymphopenia , neutropenia , and nausea/vomiting ( 11.1 % each ) . One patient died from pneumonia and one patient died from pulmonary thromboembolism . Pretreatment levels of angiogenesis biomarkers , microparticles , and microparticle-related procoagulant activity were elevated in patients compared with healthy volunteers . This regimen is feasible , but failed to improve the results obtained with other second-line therapies in recurrent GB There is no optimal treatment for breast cancers lacking estrogen ( ER ) and progesterone ( PgR ) receptors in elderly women with co-morbidities that prevent use of " st and ard chemotherapy regimens " such as AC or CMF . The CASA trial studied pegylated liposomal doxorubicin ( PLD ) and low dose , metronomic cyclophosphamide + methotrexate ( CM ) for older ( > 65 ) , vulnerable women with operable , ER and PgR-negative breast cancer . After two years the trial closed early , due to slow and inadequate accrual , with 77 patients ( 38:PLD , 36:CM , 3:nil ) . Sixty-eight percent completed PLD ; 83 % completed CM ( both 16 weeks ) . Patients on PLD reported worse quality of life , cognitive and physical functioning than non-PLD regimens ( primarily CM ) . At a median follow-up of 42 months , 81 % of r and omized patients remained free of any breast cancer recurrence . Based on our limited experience , PLD and CM may be reasonable options for further study for elderly vulnerable patients with endocrine nonresponsive breast cancer PURPOSE To evaluate the benefit of low-dose cyclophosphamide and methotrexate ( CM ) maintenance , which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer , in early breast cancer . PATIENTS AND METHODS International Breast Cancer Study Group ( IBCSG ) Trial 22 - 00 , a r and omized phase III clinical trial , enrolled 1,086 women ( 1,081 intent-to-treat ) from November 2000 to December 2012 . Women with estrogen receptor- and progesterone receptor-negative ( < 10 % positive cells by immunohistochemistry ) early breast cancer any nodal and human epidermal growth factor receptor 2 status , were r and omly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance ( cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year ) or to no CM . The primary end point was disease-free survival ( DFS ) , which included invasive recurrences , second ( breast and nonbreast ) malignancies , and deaths . RESULTS After a median of 6.9 years of follow-up , DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM , both overall ( hazard ratio [ HR ] , 0.84 ; 95 % CI , 0.66 to 1.06;P = .14 ) and in triple-negative ( TN ) disease ( n = 814 ; HR , 0.80 ; 95 % CI , 0.60 to 1.06 ) . Patients with TN , node-positive disease had a nonstatistically significant reduced HR ( n = 340 ; HR , 0.72 ; 95 % CI , 0.49 to 1.05 ) . Seventy-one ( 13 % ) of 542 patients assigned to CM maintenance did not start CM . Of 473 patients who received at least one CM maintenance dose ( including two patients assigned to no CM ) , 64 ( 14 % ) experienced a grade 3 or 4 treatment-related adverse event ; elevated serum transaminases was the most frequently reported ( 7 % ) , followed by leukopenia ( 2 % ) . CONCLUSION CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer . The trend toward benefit observed in the TN , node-positive subgroup supports additional exploration of this strategy in the TN , higher-risk population This phase III , open-label , r and omized , controlled study aim ed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma . Patients were r and omized 1:1 to receive up to eight 3-week cycles of bortezomib ( 1.3 mg/m2 ) and dexamethasone ( 20 mg ; VD ; n = 48 ) or bortezomib-dexamethasone plus oral cyclophosphamide ( 50 mg ; VCD ; n = 48 ) . Median time to progression ( primary endpoint ) was slightly longer in the VD versus VCD group ( 12.6 vs 9.9 months , P = 0.192 ) , and the hazard ratio for disease progression was in favor of VD ( hazard ratio = 0.71 , 95 % confidence interval = 0.43–1.19 , P = 0.196 ) . The overall response rate was 74 % with VD and 70 % with VCD . Most adverse events were similar in frequency between arms ; however , grade ≥ 3 peripheral neuropathy was more frequent in the VCD versus VD arm ( 15 vs 4 % ) . Infection rate was higher in the VCD arm ( 64 vs 52 % ) ; however , grade ≥3 infection rates were comparable ( 19 vs 17 % ) . Further trials are needed to determine whether addition of cyclophosphamide to VD at a different dose/schedule confers clinical benefit . This study was terminated prematurely , with insufficient sample size to adequately compare the arms ; the results should , therefore , be considered descriptive . This trial is registered : EudraCT Number 2008 - 003213 - 27 ; Clinical Trials.gov NCT00813150 BACKGROUND In this phase II trial , we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas ( MGs ) . METHODS Eligible patients received daily temozolomide ( 50 mg/m2 ) continuously until progression . The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort ( N = 37 ) . In an exploratory analysis , 10 additional recurrent grade III MG patients were enrolled . Correlative studies included evaluation of 76 frequent mutations in glioblastoma ( iPLEX assay , Sequenom ) aim ing at establishing the frequency of potentially " drugable " mutations in patients entering recurrent MG clinical trials . RESULTS Among glioblastoma patients , median age was 56 y ; median Karnofsky performance score ( KPS ) was 80 ; 62 % of patients had been treated for ≥2 recurrences , including 49 % of patients having failed bevacizumab . Treatment was well tolerated ; clinical benefit ( complete response + partial response + stable disease ) was seen in 10 ( 36 % ) patients . Progression-free survival rate at 6 months was 19 % and median overall survival was 7 months . Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients ( median overall survival : 4.3 mo vs 13 mo ; hazard ratio = 3.2 ; P = .001 ) , but those patients had lower KPS ( P = .04 ) and higher number of recurrences ( P < .0001 ) . Mutations were found in 13 of the 38 MGs tested , including mutations of EGFR ( N = 10 ) , IDH1 ( N = 5 ) , and ERBB2 ( N = 1 ) . CONCLUSIONS In spite of a heavily pretreated population , including nearly half of patients having failed bevacizumab , the primary endpoint was met , suggesting that this regimen deserves further investigation . Results in bevacizumab-naive patients seemed particularly favorable , while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG . Clinical trials.gov identifier NCT00498927 ( available at http:// clinical trials.gov/ct2/show/NCT00498927 ) Fulvestrant is effective in postmenopausal women with estrogen receptor-positive advanced breast cancer ( ABC ) . So far , no published data exist on fulvestrant combined with chemotherapy . We retrospectively assessed the role of combining oral metronomic cyclophosphamide and methotrexate ( CM ) to fulvestrant in two cohorts ( A and B ) of heavily pre-treated estrogen receptor-positive advanced ABC patients . From October 2006 to September 2009 , 33 postmenopausal patients received fulvestrant 250 mg via i.m . injection q28 days . In A , 20 patients added metronomic cyclophosphamide ( 50 mg p.o . daily ) and methotrexate ( 2.5 mg p.o . twice daily on day 1 and day 4 weekly ) after disease progression , continuing fulvestrant at the same dose . In B , 13 patients started fulvestrant plus metronomic CM upfront . Thirty-two patients were evaluable for response . Clinical benefit ( partial response + stable disease > 24 months ) for A + B was 56 % ( 95 % CI 38 - 74 % ) . The addition of metronomic CM did not determine relevant toxicities . Treatment with fulvestrant plus metronomic CM was effective in advanced ABC and was minimally toxic providing long-term disease control in a high proportion of patients . The prolonged clinical benefit , often desirable in such patients , supports this regimen as an additional and useful therapeutic tool BACKGROUND The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers . PATIENTS AND METHODS We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF ( epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses ) followed by paclitaxel ( 90 mg/m(2 ) ) on day 1 , 8 , and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer ( T2-T4a-d , N0 - 3 , M0 ) with estrogen receptor and progesterone receptor < 10 % . RESULTS We enrolled 34 patients from June 2009 to May 2013 . All were considered evaluable on an intention-to treat basis . The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41 % ( 95 % confidence interval [ CI ] , 30 - 51 ; P < .0001 ) for the entire population , and 22 % ( 95 % CI , 7 - 38 ; P = .0097 ) in patients who did not achieve pathological complete response ( pCR ) . Responses to the treatment were obtained in 31 patients [ 91 % ] of the patients , and 19 patients ( 56 % ; 95 % CI , 35 - 70 ) had a pCR . Stable disease was observed in 3 patients and none had progressive disease . Grade ≥ 3 hematologic adverse events included leukopenia in 9 % ( 3 of 34 ) , neutropenia in 38 % ( 13 of 34 ) , and anemia in 3 % ( 1 of 34 ) of patients . Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient . CONCLUSION A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective , with high pCR rates , reduction of Ki-67 , and it was associated with a low toxicity profile Aim : To explore the feasibility and activity of oral metronomic vinorelbine patients with advanced NSCLC not eligible to st and ard chemotherapy because of old age ( ≥70 years ) , and /or poor Eastern Cooperative Oncology Group performance status ( ≥2 ) , and /or extensive brain or bone disease , and /or active comorbidities ( ≥2 ) requiring for pharmacological treatment . Patients and Methods : In a prospect i ve phase II not r and omized study , patients with stage IV NSCLC unfit to chemotherapy were treated with oral metronomic vinorelbine at 30 mg fixed dose three times a week until disease progression . Results : Fifty patients were treated , 19 ( 38 % ) in the first-line setting . Five patients ( 11 % ) experienced a grade 3 toxicity ; no grade 4 toxicity occurred . Overall disease control rate was 32 % , 44 % and 26 % in first and subsequent lines , respectively ( p=0.39 ) . Median OS and PFS were 7.3 months ( 95 % confidence interval [CI]=4.7 - 10.0 ) and 2.7 months ( 95%CI=2.0 - 3.4 ) , respectively . Conclusion : These data support the activity and safety of metronomic vinorelbine in a relevant proportion of patients usually excluded from any specific treatment ABSTRACT The metronomic therapy concept uses low doses of continuously applied chemotherapeutic , anti-angiogenetic , and immunomodulating drugs . Twenty patients with recurrent and 3 with refractory high-risk neuroblastoma were treated by the metronomic concept using celecoxib , cyclophosphamide , vinblastine , and etoposide for up to 24 months . The outcome was compared to 274 matched patients with a first recurrence from stage 4 neuroblastoma using the variables time from diagnosis to first recurrence , number of organs involved , and MYCN amplification . All were treated with dose-intensive conventional chemotherapy . The study patients experienced 1–3 recurrences and had 1–3 sites involved ( osteomedullary , primary tumor , central nervous system , lymph nodes , liver , lungs ) before the metronomic therapy started . Two patients in complete remission and three with active refractory disease following recurrence treatment were excluded from the outcome analysis . The curves for secondary event-free and overall survival demonstrated no significant differences . The toxicity was minimal except for ≥3 grade thrombocytopenia and leukopenia ( all heavily pretreated ) . The treatment was realized in an outpatient setting . The metronomic approach is similarly effective as st and ard treatment in recurrent high-risk neuroblastoma , has low toxicity , and is applicable in an outpatient setting . A prospect i ve study including propranolol as a fifth drug is underway Background The primary aim of this trial was to determine the recommended phase II dose ( RP2D ) of weekly paclitaxel ( wP ) administered in combination with oral metronomic cyclophosphamide ( OMC ) . Methods Patients ≥ 18 years of age with refractory metastatic cancers were eligible if no st and ard curative measures existed . Paclitaxel was administered IV weekly ( D1 , D8 , D15 ; D1 = D28 ) in combination with a fixed dose of OMC ( 50 mg twice a day ) . A 3 + 3 design was used for dose escalation of wP ( 40 to 75 mg/m2 ) followed by an expansion cohort at RP2D . Dose-limiting toxicity ( DLT ) was defined over the first 28-day cycle as grade ≥ 3 non-hematological or grade 4 hematological toxicity ( NCI-CTCAE v4.0 ) or any toxicity leading to a dose reduction . Results In total , 28 pts . ( 18 in dose-escalation phase and 10 in expansion cohort ) were included , and 16/18 pts . enrolled in the dose-escalation phase were evaluable for DLT . DLT occurred in 0/3 , 1/6 ( neuropathy ) , 0/3 and 2/4 pts . ( hematological toxicity ) at doses of 40 , 60 , 70 and 75 mg/m2 of wP , respectively . The RP2D of wP was 70 mg/m2 ; 1/10 patients in the expansion phase had a hematological DLT . At RP2D ( n = 14 ) , the maximal grade of drug-related adverse event was Gr1 in three patients , Gr2 in six patients , Gr3 in one patient and Gr4 in one patient ( no AE in three patients ) . At RP2D , a partial response was observed in one patient with lung adenocarcinoma . Conclusion The combination of OMC and wP result ed in an acceptable safety profile , warranting further clinical evaluation . Trial registration TRN : NCT01374620 ; date of registration : 16 June 2011 Abstract Introduction : Frequent administration of low doses of cytotoxic drugs ( metronomic chemotherapy ) has been suggested to suppress tumour growth possibly by inhibiting angiogenesis . We evaluated a metronomic regimen of oral vinorelbine in pre-treated patients with advanced non-small cell lung cancer ( NSCLC ) . Methods : Forty-six pre-treated NSCLC patients received oral vinorelbine at a fixed dose of 50 mg three times a week . Results : Treatment was administered as second-line in 12 ( 26·1 % ) patients and as third- or further-line in 34 ( 73·9 % ) . Grade 3–4 neutropenia was observed in 23·9 % and febrile neutropenia in 10·9 % . Grade 3 fatigue was the most common severe non-hematologic toxicity ( 10·9 % ) . Response rate was 10·9 % ; 19·6 % achieved disease stabilization . Median tumour progression ( TTP ) was 2·2 months , median overall survival 9·4 months and the 1-year survival rate was 30·1 % . Conclusion : The administration of metronomic oral vinorelbine is feasible and results in acceptable clinical efficacy associated with manageable toxicity in a population consisting mostly of heavily pre-treated NSCLC patients |
586 | 24,589,465 | This study demonstrates that CRP may have a critical prognostic value in patients with prostatic cancer | Several studies have reported that C-reactive protein ( CRP ) , an inflammation biomarker , may be associated with the prognosis of prostate cancer ( PCa ) .
The objective of this systematic review is to summarize the predictive role of CRP for survival in PCa as reported in previous studies . | Interleukin‐6 ( IL‐6 ) and C‐reactive protein ( CRP ) are elevated in prostate cancer patients , but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear . We undertook a large , prospect i ve case‐control study to evaluate the relation between prediagnostic levels of IL‐6 and CRP and prostate cancer incidence and mortality . We also investigated the role of the IL‐6 ( −174 G/C ) polymorphism in relation to circulating levels of IL‐6 and CRP , as well as cancer risk and mortality . We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk . For analyses of prostate cancer mortality , we conducted survival analyses in cases . Because of the strong link between inflammatory markers and body mass index ( BMI ) , we assessed interactions between BMI and plasma levels on prostate cancer outcomes . Neither IL‐6 nor CRP plasma levels varied significantly by IL‐6 genotype . Genotype was not associated with prostate cancer risk or survival . Though neither IL‐6 nor CRP was associated with prostate cancer incidence overall , we observed a statistically significant interaction between IL‐6 and BMI on prostate cancer incidence ( pinteraction < 0.01 ) . Increasing IL‐6 levels were positively associated with risk in healthy weight men , but inversely associated with risk in overweight men . Further , prediagnostic IL‐6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases ( ptrend = 0.02 ) . Adjusted hazard ratios were 1.73 ( 95 % CI : 0.86 , 3.51 ) comparing the highest to lowest IL‐6 level . Our study suggests that IL‐6 may potentially be involved in the development or progression of prostate cancer . © 2008 Wiley‐Liss , |
587 | 28,742,235 | There were no statistically significant differences in infection rates and surgical procedures between nanocrystalline silver , silver-impregnated hydrofiber dressing , and silver-impregnated foam dressing ; however , nanocrystalline silver was found to be the most beneficial for all the outcomes , including infection rates and surgical procedures , according to the Monte Carlo simulation method .
In conclusion , current evidence from the published literature suggests that where the clinical and microbiological priority is to get in control of infection quickly it would seem prudent to use the most potent silver delivery system , which is nanocrystalline silver .
Nanocrystalline silver may offer both clinical and economic benefits compared to alternative treatments in the management of patients with mixed burns that are at high risk of infection | Silver-containing products play an important role in the management of burn wound infections .
We sought to compare the efficacy of commonly used silver delivery approaches including nanocrystalline silver , silver-impregnated hydrofiber dressing , and silver-impregnated foam dressing as the main products in the management of partial thickness burns . | Background . Infections are the major life-threatening complication of burn injury and occur with the greatest frequency in children . Knowledge of their occurrence and management , however , is extrapolated from studies in adults . We performed a prospect i ve study of infectious complications in burned children . Objective . To delineate epidemiology , risk factors and microbiology of infections in burned children where burn care and surgical interventions are optimal . Methods . Children hospitalized for burns were entered into prospect i ve study . Characteristics of the burn injury were assessed , and active surveillance for infections was performed . Results . Seventy patients were entered [ mean age , 42 months ; mean total body surface area ( TBSA ) , burn 15 % ] . Twenty-seven percent of patients developed 39 infections : 13 involved the burn wound ( burn wound sepsis , 6 ; graft loss , 5 ; and cellulitis , 2 ) ; 13 were catheter-associated septicemia ; 13 involved other sites ( i.e. pneumonia , 4 ; urinary tract infection , 3 ; bacteremia , 2 ; endocarditis , 1 ; myocardial abscess , 1 ; toxin-mediated syndrome , 1 ; and otitis media , 1 ) . Twenty-three infections were caused by a single organism , 9 infections by more than 1 organism and in 7 infections defined by CDC criteria no organism was recovered . Organisms causing infection were : Staphylococcus aureus , 19;C and ida albicans , 4;Pseudomonas aeruginosa , 4 ; coagulase-negative Staphylococcus , 4;Enterococcus sp. , 3;Escherichia coli , 1;Klebsiella oxytoca , 1;Serratia marcescens , 1;Streptococcus pneumoniae , 1;Streptococcus pyogenes , 1;Aspergillus fumigatus , 1 ; and C and ida parapsilosis , 1 . Burn mechanism ( flame and inhalation ) , extent ( TBSA > 30 % ) and depth ( full thickness ) were risk factors for infection ; young age and site of burn were not . Conclusion . The most common infections occurring in burn children are burn wound infections and catheter-associated septicemia . Characteristics of burn injury predict risk of infection . Children with flame and inhalation injury , TBSA burned > 30 % and full thickness burns are at high risk of infectious complications This prospect i ve , r and omized study compared protocol s of care using either AQUACEL ® Ag Hydrofiber ® ( ConvaTec , a Bristol-Myers Squibb company , Skillman , NJ ) dressing with silver ( n = 42 ) or silver sulfadiazine ( n = 42 ) for up to 21 days in the management of partial-thickness burns covering 5 % to 40 % body surface area ( BSA ) . AQUACEL ® Ag dressing was associated with less pain and anxiety during dressing changes , less burning and stinging during wear , fewer dressing changes , less nursing time , and fewer procedural medications . Silver sulfadiazine was associated with greater flexibility and ease of movement . Adverse events , including infection , were comparable between treatment groups . The AQUACEL ® Ag dressing protocol tended to have lower total treatment costs ( $ 1040 vs. $ 1180 ) and a greater rate of re-epithelialization ( 73.8 % vs 60.0 % ) , result ing in cost-effectiveness per burn healed of $ 1,409.06 for AQUACEL ® Ag dressing and $ 1,967.95 for silver sulfadiazine . A protocol of care with AQUACEL ® Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns OBJECTIVE To investigate and evaluate the clinical efficacy and safety of Acticoat with nanocrystalline silver for external use on the management of the residual wounds post-burn . METHODS One hundred and sixty-six wounds of 98 burn patients were enrolled and divided into Acticoat group and silver sulfadiazine group in the multi-center r and omized clinical trial . Acticoat was used as the treated group for those who have redness , swelling , and excessive secretion ( " heavy " exu date s ) in the wound , Acticoat was changed once a day . When there is not much secretion in the wound , or redness and swelling were not obvious , the dressings were changed once every 3 days . Silver sulfadiazine ( SD-Ag ) was used as control group , which was treated under the usual clinical routine . Healing time was observed up to 20 days . Healing percentage on the 15th day after treatment was determined . RESULTS Healing time was 12.42+/-5.40 days after the application of Acticoat . This was significantly shorter than that of control wounds . The wounds of the trial group healed nearly 3.35 days earlier than the control ones . Healing percentage at 15 days in the trial wounds was 97.37 % , which was higher than the control , but there was no significant difference between them . The bacterial clearance rate of the Acticoat group on the 6th and 12th day post-treatment was 16.67 and 26.67 % , respectively , which was significantly higher than the control . CONCLUSIONS Acticoat with nanocrystalline silver promotes the healing process of residual wounds post-burn effectively . No adverse reaction of Acticoat was found during the study Silver sulfadiazine has been used as a topical burn wound treatment for many years . Pain associated with dressing changes is a common problem in burn wounds . Aquacel Ag , a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity . The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns . This prospect i ve r and omized study was conducted in 70 patients who had partial thickness burns less than 15 % of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006-February 2008 . Patients were divided into two groups : Aquacel Ag-treated group with dressing changes every 3 days ( 35 patients ) and 1 % silver sulfadiazine-treated group , with daily dressing changes ( 35 patients ) . There was no difference in demographic data including age , gender , burn percentage between groups . Time-to-wound healing pain score during dressing change and cost of treatment were compared between both groups . Time-to-wound closure was significantly shorter in the Aquacel Ag-treated group ( 10 + /- 3 versus 13.7 + /- 4 days , P < 0.02 ) as well as pain scores at days 1 , 3 and 7 ( 4.1 + /- 2.1 , 2.1 + /- 1.8 , 0.9 + /- 1.4 versus 6.1 + /- 2.3 , 5.2 + /- 2.1 , 3.3 + /- 1.9 , respectively , P < 0.02 ) . Total cost of treatment was 52 + /- 29 US dollars for the Aquacel Ag-treated group versus 93 + /- 36 US dollars for the silver sulfadiazine-treated group . This study showed that Aquacel Ag increased time to healing , decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost . This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The very first rigorously design ed , r and omized controlled trial ( RCT ) in the history of modern medicine was published in 1948 . The study , design ed and carried out by the Streptomycin in Tuberculosis Trials Committee of the Medical Research Council , demonstrated the efficacy of streptomycin in treating pulmonary tuberculosis on top of bed rest , which was the best available treatment at that time.1 In the field of hypertension treatment and cardiovascular prevention , the history of event-based RCTs began in 1967 , when the cardiovascular benefits and risks of antihypertensive drug treatment were evaluated in the setting of the Veterans Administration Cooperative Study in Hypertension.2 In that trial , 143 patients with severe hypertension were r and omized to receive blood pressure (BP)–lowering drug treatment or matched placebo for 11 months . A major morbid or fatal event was observed in 26 of 70 patients who received placebo ( 37 % ) and in only 1 of 73 patients under active treatment ( 1 % ) . The amazing results of this l and mark trial established beyond any doubt the striking cardiovascular benefits of antihypertensive drug treatment of hypertension at a time when controversy still persisted regarding the supposedly deleterious effects of BP reduction on organ perfusion.3 Ever since , RCTs have represented a formidable tool for evaluating risks and benefits of hypertension treatment . Over the past 50 years , the remarkable progress in treatment and control of high BP , one of the most outst and ing achievements of modern medicine , has been driven by the results of many large , event-based RCTs . The influential position of RCTs in clinical and therapeutic research as opposed to real-world observational studies ( surveys , registries , and retrospective analyses of existing data bases ) originates from their high internal validity ( ie , the power to address clinical questions with a low level of internal bias ) . A list of strengths and weaknesses of RCTs and observational studies is BACKGROUND Partial-thickness burns are among the most frequently encountered types of burns , and numerous dressing material s are available for their treatment . A multicenter , open , r and omized , and parallel study was undertaken to determine the efficacy and tolerability of silver sulfadiazine ( SSD ) compared with an absorbent foam silver dressing , Mepilex Ag , on patients aged between 5 years and 65 years with deep partial-thickness thermal burn injuries ( 2.5–25 % total body surface area ) . METHODS Patients were r and omly assigned to either SSD ( n = 82 ) applied daily or a Mepilex Ag dressing ( n = 71 ) applied every 5 days to 7 days . The treatment period was up to 4 weeks . RESULTS There was no significant difference between the two treatment groups with respect to the primary end point of time to healing , which occurred in 56 ( 79 % ) of 71 patients after a median follow-up time of 15 days in the Mepilex Ag group compared with 65 ( 79 % ) of 82 patients after a median follow-up time of 16 days in the SSD group ( p = 0.74 ) . There was also no significant difference in the percentage of study burn healed . Patients in the Mepilex Ag group had 87.1 % of their study burn healed ( out of the total burn area ) compared with 85.2 % of patients in the SSD group . However , the mean total number of dressings used was significantly more in the SSD group ( 14.0 ) compared with the Mepilex Ag group ( 3.06 , p < 0.0001 ) . There was no significant difference in the time until skin graft was performed between the two study groups . CONCLUSION There was no difference in healing rates between Mepilex Ag and SSD , with both products well tolerated . The longer wear time of Mepilex Ag promotes undisturbed healing and makes it easier for patients to continue with their normal lives sooner . LEVEL OF EVIDENCE Therapeutic study , level III A new silver-coating technology was developed to prevent wound adhesion , limit nosocomial infection , control bacterial growth , and facilitate burn wound care through a silver-coated dressing material . For the purpose s of this article , Acticoat ( West aim Biomedical Inc , Fort Saskatchawan , Alberta , Canada ) silver-coated dressing was used . After in vitro and in vivo studies , a r and omized , prospect i ve clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution 's st and ard burn wound care . Thirty burn patients with symmetric wounds were r and omized to be treated with either 0.5 % silver nitrate solution or Acticoat silver-coated dressing . The dressing was evaluated on the basis of overall patient comfort , ease of use for the wound care provider , and level of antimicrobial effectiveness . Wound pain was rated by the patient using a visual analog scale during dressing removal , application , and 2 hours after application . Ease of use was rated by the nurse providing wound care . Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment . Patients found dressing removal less painful with Acticoat than with silver nitrate , but they found the pain to be comparable during application and 2 hours after application . According to the nurses , there was no statistically significant difference in the ease of use . The frequency of burn wound sepsis ( > 10(5 ) organisms per gram of tissue ) was less in Acticoat-treated wounds than in those treated with silver nitrate ( 5 vs 16 ) . Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds ( 1 vs 5 ) . Acticoat dressing offers a new form of dressing for the burn wound , but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care INTRODUCTION Studies comparing contemporary silver dressings in burns are scarce . METHODS In a prospect i ve , r and omized , controlled study , counting 50 patients / research group , we compared two frequently used silver dressings , Acticoat ™ and Aquacel ( ® ) Ag , in the management of partial thickness burns with a predicted healing time between 7 and 21 days as assessed by laser Doppler imaging between 48 and 72h after burn . Variables investigated were related to baseline research group characteristics , wound healing , bacteriology , economics , nurse , and patient experience . RESULTS Both research groups were comparably composed taking into account gender , age and burn characteristics . Similar results were obtained as to healing time and bacterial control with both silver dressings . A statistically significant difference in favor of the Aquacel ( ® ) Ag dressing was found for average ease of use ( p<0.001 ) , average ease of application ( p=0.001 ) , patient pain ( p<0.001 ) , patient comfort with the dressing ( p=0.017 ) , silver staining ( p<0.001 ) , and cost effectiveness ( p<0.001 ) . CONCLUSION Both silver dressings result ed in comparable healing times and bacterial control but the Aquacel ( ® ) Ag dressing significantly increased comfort for patients as well as nurses and was significantly more cost-effective than the Acticoat ™ dressing for the given indication OBJECTIVE : The purpose of this investigation was to determine the effectiveness of silver sulfadiazine as compared with Aquacel Ag in patients with superficial partial-thickness burns . METHODS : Twenty-four subjects who sustained superficial partial-thickness burns who were between the ages of 19 and 53 years with time of injury from 0 to 4 days were r and omly assigned into a control group ( silver sulfadiazine ) and experimental group ( Aquacel Ag ; ConvaTec , Skillman , New Jersey ) . Wound measurements were assessed at the time of the initial examination and every 4 days afterward until the area was re-epithelialized 100 % . To ensure objectivity , the burn area was measured digitally with the software program by Aspyra ( Aspyra LLC ; Blue Springs , Missouri ) to prevent discrepancies in wound measurements . RESULTS : Significant differences between the silver sulfadiazine and Aquacel Ag group were noted in pain ( silver sulfadiazine : 4.70 ± 2.22 , Aquacel Ag : 2.92 ± 1.12 ) and the number of treatments ( silver sulfadiazine : 10.27 ± 7.46 , Aquacel Ag : 4.10 ± 1.38 ) . CONCLUSIONS : Utilization of Aquacel Ag in superficial-partial thickness burns could lead to a decrease in the number of treatments required to re-epithelialize burns 100 % with less pain as compared with silver sulfadiazine 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 Despite recent improvements in analgesia , pain control during dressing changes continues to be a major challenge in patients with burns . We investigated two different dressing modalities to compare how much pain the patient experienced during and after the dressing change . Patients with partial-thickness burns that required only topical wound care were assigned r and omly to treatment with Acticoat ( Smith and Nephew USA , Largo , FL ) or silver sulfadiazine ( AgSD ) . The outcome variable was pain during wound care , which was measured using visual analog pain scores . The mean visual analog pain scores for the wounds treated with Acticoat or AgSD wounds were 3.2 and 7.9 , respectively ( P < .0001 ; paired Student 's t-test ) . In 41 of the 47 paired pain score observations , the pain in the wound treated with AgSD was perceived as greater than in the wound treated with Acticoat . Burn wound care with Acticoat is less painful than burn wound care with AgSD in patients with selected partial-thickness burns AIM / PURPOSE The aim of this study was to compare clinical outcome of children with scald burns treated with a hydrofiber dressing ( Aquacel ( ® ) , Convatec Inc. ) with the former st and ard of care with silver sulfadiazine ( Flammazine ( ® ) ; Solvay Pharmaceuticals ) , considering surgical intervention and length of stay ( LOS ) . METHODS A retrospective study of all consecutive children from zero to four years with primary scald burns up to 10 % admitted to the Burn Centre of the Maasstad Hospital Rotterdam between January 1987 and January 2010 were review ed . For data collection a prospect i ve computerized data base was used . For comparison the study period was divided into two periods representing the period before and after the introduction of the hydrofiber dressing ( HFD ) , respectively 1987 - 1999 ( period 1 ) and 1999 - 2010 ( period 2 ) . RESULTS Over the whole study period 27.3 % of 502 patients treated with silver sulfadiazine ( Ag-SD ) underwent surgery , while before the introduction of HFD 30.5 % of 338 Ag-SD treated patients were operated upon . After the introduction of the HFD 20.7 % of 164 patients treated with Ag-SD eventually underwent skin grafting , a significant difference with the 11.6 % of 302 patients whose wounds were dressed with HFD ( p<0.01 ) . CONCLUSIONS Compared to silver sulfadiazine treatment a reduced number of surgical interventions was observed in mixed partial thickness scald burns up to 10 % TBSA burned in children aged 0 - 4 years after the introduction of hydrofiber dressings . The mode of treatment with this wound dressing also limited hospital length of stay |
588 | 27,382,306 | Subgroup analyses suggested that neurotoxicity was associated with GSTM1 polymorphism in the Asian population , neutropenia was associated with GSTM1 polymorphism in palliative chemotherapy and older patients ( mean age > 60 years ) , and tumor response was associated with GSTT1 polymorphism in gastric cancer and responders defined by complete and partial responses . | Background Gastric and colorectal cancers remain the major causes of cancer-related death .
Although chemotherapy improves the prognosis of the patients with gastrointestinal cancers , some patients do not benefit from therapy and are exposed to the adverse effects .
The polymorphisms in genes including GSTM1 and GSTT1 have been explored to predict therapeutic efficacy ; however , the results were inconsistent and inconclusive . | Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy . Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI The discovery of pharmacogenomic markers in colorectal cancer ( CRC ) could be setting -specific . FOLFOX4 is employed in the adjuvant and metastatic setting in CRC . This prospect i ve study is aim ed to vali date in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting ( that is , GSTP1-rs947894 , and -rs1138272 ; GSTM1-null genotype ; AGXT-rs4426527 , -rs34116584 and del-74 bp ) , and to discover additional markers . CRC patients ( n=144 ) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes . Grade ⩾2 neurotoxicity was associated ( false discovery rate-adjusted q-value < 0.1 ) with single-nucleotide polymorphisms in ABCC1 ( rs2074087 : odds ratio=0.43(0.22–0.86 ) ) , and ABCC2 ( rs3740066 : 2.99(1.16–7.70 ) ; rs1885301 : 3.06(1.35–6.92 ) ; rs4148396 : 4.69(1.60–13.74 ) ; rs717620 : 14.39(1.63–127.02 ) ) . hMSH6-rs3136228 was associated with grade 3–4 neutropenia ( 3.23(1.38–7.57 ) , q-value=0.0937 ) . XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity ( 8.90(2.48–31.97 ) , q-value=0.0150 ) . The markers previously identified in metastatic CRC were not vali date d. We have identified new markers of toxicity in genes of transport and DNA repair . If vali date d in other studies , they could help to identify patients at risk of toxicity Purpose The aim of this study was to assess whether genetic polymorphisms in p53 , glutathione S-transferase P1 ( GSTP1 ) , GSTM1 , excision repair cross complementing group 1 ( ERCC1 ) and X-ray repair cross-complementing group 1 ( XRCC1 ) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy . Methods The genetic polymorphisms in p53 , GSTP1,GSTM1 ( null ) , ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method . Results Among the five studied polymorphisms , p53 codon 72 Pro/Pro , GSTP1 codon 105 Ile/Ile , and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival ( P < 0.05 ) ; and the prognostic effect was retained in the Cox multivariate analysis . Combination analysis with the three polymorphisms using the Kaplan – Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes ( P < 0.05 ) . No significant association was found between the GSTM1 ( null ) or the ERCC1 codon 118 genotypes and the clinical outcome ( P > 0.05 ) . Conclusion Testing for p53 Arg72Pro , GSTP1 Ile105Val , and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy . Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospect i ve studies Purpose : To explore the effect of dihydropyrimidine dehydrogenase ( DPD ) single nucleotide polymorphisms ( SNP ) and haplotypes on outcome of capecitabine . Experimental Design : Germline DNA was available from 568 previously untreated patients with advanced colorectal cancer participating in the CAIRO2 trial , assigned to capecitabine , oxaliplatin , and bevacizumab ± cetuximab . The coding region of dihydropyrimidine dehydrogenase gene ( DPYD ) was sequenced in 45 cases with grade 3 or more capecitabine-related toxicity and in 100 r and omly selected controls ( cohort ) . Most discriminating ( P < 0.1 ) or frequently occurring ( > 1 % ) nonsynonymous SNPs were analyzed in all 568 patients . SNPs and haplotypes were associated with toxicity , capecitabine dose modifications , and survival . Results : A total of 29 SNPs were detected in the case – cohort analysis , of which 8 were analyzed in all 568 patients . Of the patients polymorphic for DPYD IVS14 + 1G > A , 2846A > T , and 1236G > A , 71 % ( 5 of 7 ) , 63 % ( 5 of 8) , and 50 % ( 14 of 28 ) developed grade 3 to 4 diarrhea , respectively , compared with 24 % in the overall population . All patients polymorphic for IVS14 + 1G > A developed any grade 3 to 4 toxicity , including one possibly capecitabine-related death . Because of toxicity , a mean capecitabine dose reduction of 50 % was applied in IVS14 + 1G > A and 25 % in 2846A > T variant allele carriers . Patients were categorized into six haplotype groups : one predicted for reduced ( 10 % ) , and two for increased risks ( 41 % and 33 % ) for severe diarrhea . Individual SNPs were not associated with overall survival , whereas one haplotype was associated with overall survival [ HR ( 95 % CI ) = 0.57 ( 0.35–0.95 ) ] . Conclusions : DPYD IVS14 + 1G > A and 2846A > T predict for severe toxicity to capecitabine , for which patients require dose reductions . Haplotypes assist in selecting patients at risk for toxicity to capecitabine . Clin Cancer Res ; 17(10 ) ; 3455–68 . © 2011 AACR PURPOSE The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin , folinic acid , and fluorouracil palliative chemotherapy . MATERIAL S AND METHODS Consecutive patients were prospect ively enrolled onto medical oncology units in Central Italy . Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion . Peripheral blood sample s were used for genotyping 12 polymorphisms in thymidylate synthase , methylenetetrahydrofolate reductase , xeroderma pigmentosum group D ( XPD ) , excision repair cross complementing group 1 ( ERCC1 ) , x-ray cross complementing group 1 , x-ray cross complementing protein 3 , glutathione S-transferases ( GSTs ) genes . The primary end point of the study was to investigate the association between genotypes and progression-free survival ( PFS ) . RESULTS In 166 patients , ERCC1 - 118 T/T , XPD-751 A/C , and XPD-751 C/C genotypes were independently associated with adverse PFS . The presence of two risk genotypes ( ERCC1 - 118 T/T combined with either XPD-751 A/C or XPD-751 C/C ) occurred in 50 patients ( 31 % ) . This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84 % and 95 % CI of 1.47 to 5.45 ( P = .002 ) . Neurotoxicity was significantly associated with GSTP1 - 105 A/G. Carriers of the GSTP1 - 105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1 - 105 A/G and GSTP1 - 105 A/A genotypes . CONCLUSION A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer . These findings deserve confirmation in additional prospect i ve studies PURPOSE To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Peripheral blood sample s from 175 prospect ively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes ( TS , MTHFR , XPD , ERCC1 , XRCC1 , XRCC3 , GSTPI , GSTTI , GSTMI ) . Genotypes were correlated to response and survival . RESULTS The overall response rate was 41 % , the median progression-free survival ( PFS ) was 24 weeks ( range , 4 to 50 weeks ) , and the median overall survival ( OS ) was 39 weeks ( range , 8 to 72 + weeks ) . Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype ( 2R/3 G , 3C/3 G , 3G/3 G ) and GSTP1 105 A/A homozygous genotype . Sixty-one patients ( 35 % ) did not show any of these risk genotypes ( group 0 ) , 57 patients ( 32.5 % ) showed one of the two risk genotypes ( group 1 ) , and 57 patients ( 32.5 % ) showed both risk genotypes ( group 2 ) . Median PFS and OS in group 0 patients were 32 weeks ( range , 8 to 50 weeks ) and 49 weeks ( range , 18 to 72 + weeks ) , respectively . Group 1 and group 2 patients showed significantly worse PFS ( median , 26 weeks [ range , 6 to 44 weeks ] and 14 weeks [ range , 4 to 38 weeks ] , respectively ) and worse OS ( median , 39 weeks [ range , 10 to 58 weeks ] and 28 weeks [ range , 8 to 56 weeks ] ) , respectively , than group 0 patients . This adverse effect was retained in multivariate analysis . CONCLUSION Specific polymorphisms may influence clinical outcomes of AGC patients . Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospect i ve studies We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene ( DPYD ) variants to predict severe early-onset fluoropyrimidine ( FP ) toxicity , in particular of a recently discovered haplotype hapB3 and a linked deep intronic splice site mutation c.1129 - 5923C > G. Selected regions of DPYD were sequenced in prospect ively collected germline DNA of 500 patients receiving FP-based chemotherapy . Associations of DPYD variants and haplotypes with hematologic , gastrointestinal , infectious , and dermatologic toxicity in therapy cycles 1 - 2 and result ing FP-dose interventions ( dose reduction , therapy delay or cessation ) were analyzed accounting for clinical and demographic covariates . Fifteen additional cases with toxicity-related therapy delay or cessation were retrospectively examined for risk variants . The association of c.1129 - 5923C > G/hapB3 ( 4.6 % carrier frequency ) with severe toxicity was replicated in an independent prospect i ve cohort . Overall , c.1129 - 5923G/hapB3 carriers showed a relative risk of 3.74 ( RR , 95 % CI = 2.30 - 6.09 , p = 2 × 10(-5 ) ) for severe toxicity ( grade s 3 - 5 ) . Of 31 risk variant carriers ( c.1129 - 5923C > G/hapB3 , c.1679T > G , c.1905 + 1G > A or c.2846A > T ) , 11 ( all with c.1129 - 5923C > G/hapB3 ) experienced severe toxicity ( 15 % of 72 cases , RR = 2.73 , 95 % CI = 1.61 - 4.63 , p = 5 × 10(-6 ) ) , and 16 carriers ( 55 % ) required FP-dose interventions . Seven of the 15 ( 47 % ) retrospective cases carried a risk variant . The c.1129 - 5923C > G/hapB3 variant is a major contributor to severe early-onset FP toxicity in Caucasian patients . This variant may substantially improve the identification of patients at risk of FP toxicity compared to established DPYD risk variants ( c.1905 + 1G > A , c.1679T > G and c.2846A > T ) . Pre-therapeutic DPYD testing may prevent 20 - 30 % of life-threatening or lethal episodes of FP toxicity in Caucasian patients |
589 | 20,544,152 | Strong evidence for predicting outcome at 6 months was found for the Glasgow Coma Scale ( GCS ) , GCS admission , motor score , midline shift on computed tomography scan , subdural haematoma and pulsatility index .
Strong evidence of no association was found for gender and intraventricular haemorrhage .
For other determinants , inconclusive or no evidence was found .
GCS , GCS on admission , motor score , midline shift , subdural haematoma and pulsatility index predicted outcome 6 months after traumatic brain injury .
Gender and intraventricular haemorrhage did not have predictive value | OBJECTIVE To systematic ally review which determinants , assessed within the first month after a moderate to severe traumatic brain injury , predict 6-month functional outcome . | BACKGROUND Interleukin ( IL ) 1 is a proinflammatory cytokine that has been identified as an important mediator of neurodegeneration induced by ischemia or traumatic brain injury . Accumulating evidence to date has suggested that the major cytokine contributing to neurodegeneration after head injury is IL-1beta rather than IL-1alpha ; however , there is no sufficient data regarding IL-1alpha in literature , and there may be an association between IL1A gene polymorphism and outcome after head injury . METHODS We performed a prospect i ve clinical study and included a recruited series of 71 patients who had head injury and were admitted to our neurosurgical unit . Severity of initial injury was assessed by the Glasgow Coma Scale . Outcome at 6 months after injury was assessed by means of the Glasgow Outcome Score . Interleukin 1alpha genotypes were determined from blood sample s by st and ard methods . RESULTS Of 40 patients with IL1A*2 , 18 ( 45 % ) had an unfavorable outcome ( dead , vegetative state , or severe disability ) compared with 7 ( 22.5 % ) of 31 without IL1A*2 ( P = .08 ) . CONCLUSION Our findings show that there is no genetic association between IL1A gene polymorphism and outcome after head injury . Further clinical studies should be design ed to confirm and further evaluate these findings BACKGROUND Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter , corpus callosum , and brainstem . OBJECTIVE To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome . DESIGN Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome . SETTING Inpatient traumatic brain injury unit . PATIENTS From 2005 to 2006 , magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age- and sex-matched controls . MAIN OUTCOME MEASURES Six fiber variables of the corpus callosum , fornix , and peduncular projections were obtained . Glasgow Outcome Scale-Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients . RESULTS At least 1 fiber variable of each region showed diffuse axonal injury-associated alterations . At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale-Extended scores . The predicted outcome scores correlated significantly with actual scores in a mixed-effects model . CONCLUSION Diffusion tensor tractography-based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome Numerous studies addressing different methods of head injury prognostication have been published . Unfortunately , these studies often incorporate different head injury prognostication models and study population s , thus making direct comparison difficult , if not impossible . Furthermore , newer artificial intelligence tools such as machine learning methods have evolved in the field of data analysis , alongside more traditional methods of analysis . This study targets the development of a set of integrated prognostication model combining different classes of outcome and prognostic factors . Method ologies such as discriminant analysis , logistic regression , decision tree , Bayesian network , and neural network were employed in the study . Several prognostication models were developed using prospect ively collected data from 513 severe closed head-injured patients admitted to the Neurocritical Unit at National Neuroscience Institute of Singapore , from April 1999 to February 2003 . The correlation between prognostic factors at admission and outcome at 6 months following injury was studied . Overfitting error , which may falsely distinguish different outcomes , was compared graphically . Tenfold cross-validation technique , which reduces overfitting error , was used to vali date outcome prediction accuracy . The overall prediction accuracy achieved ranged from 49.79 % to 81.49 % . Consistently high outcome prediction accuracy was seen with logistic regression and decision tree . Combining both logistic regression and decision tree models , a hybrid prediction model was then developed . This hybrid model would more accurately predict the 6-month post-severe head injury outcome using baseline admission parameters Background : Subjects with moderate head injury are a particular challenge for the emergency physician . They represent a heterogeneous population of subjects with large variability in injury severity , clinical course and outcome . We aim ed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department ( ED ) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre . Patients and methods : We review ed , prospect ively , 12 675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury . A total of 309 cases ( 2.4 % ) with an admission Glasgow Coma Scale ( GCS ) 9–13 were identified as having moderate head injury . The main outcome measure was an unfavourable outcome at 6 months after injury . The predictive value of a model based on main entry variables was evaluated by logistic regression analysis . Findings : 64.7 % of subjects had a computed tomographic scan that was positive for intracranial injury , 16.5 % needed a neurosurgical intervention , 14.6 % had an unfavourable outcome at 6 months ( death , permanent vegetative state , permanent severe disability ) . Six variables ( basal skull fracture , subarachnoid haemorrhage , coagulopathy , subdural haematoma , modified Marshall category and GCS ) predicted an unfavourable outcome at 6 months . This combination of variables predicts the 6-month outcome with high sensitivity ( 95.6 % ) and specificity ( 86.0 % ) . Interpretation : A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months , when applied to subjects admitted to an ED of a General Hospital with moderate head injury OBJECTIVES To identify the demographic and clinical variables related to the duration of posttraumatic amnesia after severe closed head injury ; to evaluate the usefulness of posttraumatic amnesia duration in predicting outcome at the time of hospital discharge and at 6 months after injury . SETTING Four clinical centers located in primary care hospitals . PATIENTS Three hundred fourteen severely injured subjects aged 16 years or older who did not have trauma as a result of a penetrating injury and came out of coma before hospital discharge . INTERVENTIONS Approximately half of the subjects were administered phenytoin sodium for some period after termination of coma ; 17 % were administered dexamethasone and 41 % morphine sulfate . MAIN OUTCOME MEASURES Galveston Orientation and Amnesia Test scores defined the duration of posttraumatic amnesia . The Glasgow Outcome Scale was used to grade outcome at the time of hospital discharge and at 6 months . RESULTS Older age , low initial Glasgow Coma Scale score , nonreactive pupil(s ) , coma duration , and use of phenytoin were associated with a longer duration of posttraumatic amnesia . Poor pupillary response , time in coma , and duration of posttraumatic amnesia and use of phenytoin was predictive of the 6-month outcome . CONCLUSIONS The results support the prognostic usefulness of prospect ively measuring duration of posttraumatic amnesia after termination of coma . Pending replication , our findings suggest that posttraumatic amnesia duration may be a useful surrogate outcome measure for clinical trials involving interventions for acute head injury The early prediction of outcome after traumatic brain injury ( TBI ) is important for several purpose s , but no prognostic models have yet been developed with proven generalizability across different setting s. The objective of this study was to develop and vali date prognostic models that use information available at admission to estimate 6-month outcome after severe or moderate TBI . To this end , this study evaluated mortality and unfavorable outcome , that is , death , and vegetative or severe disability on the Glasgow Outcome Scale ( GOS ) , at 6 months post-injury . Prospect ively collected data on 2269 patients from two multi-center clinical trials were used to develop prognostic models for each outcome with logistic regression analysis . We included seven predictive characteristics-age , motor score , pupillary reactivity , hypoxia , hypotension , computed tomography classification , and traumatic subarachnoid hemorrhage . The models were vali date d internally with bootstrapping techniques . External validity was determined in prospect ively collected data from two relatively unselected surveys in Europe ( n = 796 ) and in North America ( n = 746 ) . We evaluated the discriminative ability , that is , the ability to distinguish patients with different outcomes , with the area under the receiver operating characteristic curve ( AUC ) . Further , we determined calibration , that is , agreement between predicted and observed outcome , with the Hosmer-Lemeshow goodness-of-fit test . The models discriminated well in the development population ( AUC 0.78 - 0.80 ) . External validity was even better ( AUC 0.83 - 0.89 ) . Calibration was less satisfactory , with poor external validity in the North American survey ( p < 0.001 ) . Especially , observed risks were higher than predicted for poor prognosis patients . A score chart was derived from the regression models to facilitate clinical application . Relatively simple prognostic models using baseline characteristics can accurately predict 6-month outcome in patients with severe or moderate TBI . The high discriminative ability indicates the potential of this model for classifying patients according to prognostic risk The objective of this report is to describe the design and content of the International Mission for Prognosis And Clinical Trial ( IMPACT ) data base of traumatic brain injury which contains the complete data set from most clinical trials and organized epidemiologic studies conducted over the past 20 years . This effort , funded by the U.S. National Institutes of Health , has led to the accumulation thus far of data from 9205 patients with severe and moderate brain injuries from eight r and omized placebo controlled trials and three observational studies . Data relevant to the design and analysis of pragmatic Phase III clinical trials , including pre-hospital , admission , and post-resuscitation assessment s , information on the acute management , and short- and long-term outcome were merged into a top priority data set ( TPDS ) . The major emphasis during the first phase of study is on information from time of injury to post-resuscitation and outcome at 6 months thereby providing a unique re source for prognostic analysis and for studies aim ed at optimizing the design and analysis of Phase III trials in traumatic brain injury OBJECTIVE To investigate the value of transcranial Doppler ( TCD ) ultrasonography in evaluating the outcome of severe traumatic brain injury and to correlate the TCD values with intracranial pressure ( ICP ) and cerebral perfusion pressure ( CPP ) monitoring . METHODS A prospect i ve study was conducted to evaluate the contribution of TCD ultrasonography to neurological outcome in a series of 96 severe traumatic brain injury patients . The quantitative variables of TCD ultrasonography included the mean blood flow velocity of the middle cerebral artery ( MCA ) and pulsatility index within the first 24 hours of admission . The ICP and CPP values were a lso recorded . Outcome in 6 months postinjury was evaluated using the Glasgow Outcome Scale ( GOS 4 - 5 was considered as " good " and GOS 1 - 3 as " poor " ) . RESULTS The mean blood flow velocity of the MCA was larger than 40 cm/s in 30 ( 51 % ) patients with good outcome whereas it was less than 40 cm/s in 27 ( 73 % ) patients with poor outcome ( P<0.025 ) . The mean PI in cases of good outcome ( 34 patients , 57 % ) was lower than 1.5 whereas in poor outcome ( 30 patients , 83 % ) was higher than 1.5 ( P<0.001 ) . The correlations of ICP and CPP to pulsatility index were statistically significant ( P<0.01 ) . CONCLUSIONS TCD ultrasonography is valid in predicting the patient 's outcome of 6 months and correlates significantly with ICP and CPP values when it is performed in the first 24 hours of severe traumatic brain injury The authors conducted a study to determine the value of transcranial Doppler ( TCD ) ultrasonography in evaluating the outcome of severely head injured patients and to correlate the TCD values with those obtained from intracranial pressure ( ICP ) and cerebral perfusion pressure ( CPP ) monitoring . The authors conducted a prospect i ve study of 125 patients with severe head injury ( Glascow Coma Scale scores of less than 9 ) who underwent TCD ultrasonography according to the st and ard technique of insonating the middle cerebral artery ( MCA ) and measuring the mean blood flow velocity and pulsatility index within the first 24 hours of admission . The ICP and CPP values , as well as other clinical , analytical , and neuroimaging data , were also recorded . After 6 months , outcome was evaluated using the Glasgow Outcome Scale . Moderate disability and complete recovery were considered " good " outcome ; death , vegetative state , and severe disability were considered " poor . " In 67 patients ( 54 % ) good outcome was demonstrated whereas in 58 ( 46 % ) it was poor . The mean blood flow velocity of the MCA in patients with good outcome was 44 cm/second ; in those with poor outcomes it was 36 cm/second ( p < 0.003 ) . The mean PI in cases of good outcome was 1 whereas in poor outcome was 1.56 ( p < 0.0001 ) . The correlations of ICP and CPP to PI were statistically significant ( r2 = 0.6 ; p < 0.0001 ) . When performed in the first 24 hours of severe head injury , TCD ultrasonography is valid in predicting the patient 's outcome at 6 months and correlates significantly with ICP and CPP values Proton magnetic resonance spectroscopy ( MRS ) is being used to evaluate individuals with acute traumatic brain injury and several studies have shown that changes in certain brain metabolites ( N-acetylaspartate , choline ) are associated with poor neurologic outcomes . The majority of previous MRS studies have been obtained relatively late after injury and none have examined the role of glutamate/ glutamine ( Glx ) . We conducted a prospect i ve MRS study of 42 severely injured adults to measure quantitative metabolite changes early ( 7 days ) after injury in normal appearing brain . We used these findings to predict long-term neurologic outcome and to determine if MRS data alone or in combination with clinical outcome variables provided better prediction of long-term outcomes . We found that glutamate/glutamine ( Glx ) and choline ( Cho ) were significantly elevated in occipital gray and parietal white matter early after injury in patients with poor long-term ( 6 - 12-month ) outcomes . Glx and Cho ratios predicted long-term outcome with 94 % accuracy and when combined with the motor Glasgow Coma Scale score provided the highest predictive accuracy ( 97 % ) . Somatosensory evoked potentials were not as accurate as MRS data in predicting outcome . Elevated Glx and Cho are more sensitive indicators of injury and predictors of poor outcome when spectroscopy is done early after injury . This may be a reflection of early excitotoxic injury ( i.e. , elevated Glx ) and of injury associated with membrane disruption ( i.e. , increased Cho ) secondary to diffuse axonal injury OBJECTIVE To evaluate the effect of severe head injury on both the secretion of basal pituitary hormones and the response to exogenous synthetic hypothalamic releasing factors administration . DESIGN Prospect i ve , clinical study . SETTING General intensive care unit in a university teaching hospital , Italy . PATIENTS Comatose , head-injured patients ( n = 22 ) , all intubated and mechanically ventilated , invasively monitored without previous endocrinologic problems and substitutive therapies . INTERVENTIONS Routine neuroemergency procedures ; administration of exogenous , synthetic hypothalamic releasing hormones . MEASUREMENTS AND MAIN RESULTS Determinations of basal concentrations of growth hormone ( GH ) , prolactin ( PRL ) , thyroid-stimulating hormone ( TSH ) , triiodothyronine , and thyroxine were performed daily in the first week and on days 15 and 16 after the trauma . Plasma insulin-like growth factor-I and cortisol were also determined on days 2 , 7 , and 15 . We carried out a thyrotropin-releasing hormone ( TRH ) test for the evaluation of the PRL , TSH , and GH responses on days 1 and 16 after the trauma and a growth hormone-releasing hormone ( GHRH ) test for the evaluation of GH and PRL responses on days 2 , 7 , and 15 after the trauma . Outcome was evaluated at 6 mos with the GOS . Triiodothyronine showed low values , even if in the normal range ; thyroxine remained in the normal range . Significant increases in insulin-like growth factor-I concentrations were observed on both days 7 and 15 compared with day 2 ( p = .024 and p = .034 , respectively ) . The GH response to GHRH was significantly greater on days 7 and 15 than in the very acute phase ( p < .01 comparing days 7 and 15 vs. day 2 ) . We found a higher GH response to GHRH on day 7 in group 1 vs. group 2 ( as both peak and area under the curve , p = .018 and p = .015 , respectively ) . No difference in GH response was detected on days 2 and 15 . A " paradoxical " response of GH to TRH was observed on the day after the head trauma ( basal vs. peak , p = .002 ) but not on day 16 . The GH peak response to TRH was greater on day 1 in those patients with an unfavorable course ( group 1 vs. group 2 , p < .05 ) . The TSH response to TRH was not significantly correlated to the severity of trauma , but it was significantly ( p < .04 ) higher in group 1 than in group 2 . Finally , a " paradoxical " PRL response to GHRH administration was present on day 2 ( basal vs. peak , p=.0003 ) , day 7 ( basal vs. peak , p = .01 ) , and on day 15 after the trauma ( basal vs. peak , p = .04 ) . CONCLUSIONS Some of the responses to provocative tests have been identified as " paradoxical " and seem to have a great importance in the definition of prognosis in severe head-injured patients , specifically the GH response to TRH and the PRL response to GHRH that are significantly correlated with outcome OBJECT Decision tree analysis highlights patient subgroups and critical values in variables assessed . Importantly , the results are visually informative and often present clear clinical interpretation about risk factors faced by patients in these subgroups . The aim of this prospect i ve study was to compare results of logistic regression with those of decision tree analysis of an observational , head-injury data set , including a wide range of secondary insults and 12-month outcomes . METHODS One hundred twenty-four adult head-injured patients were studied during their stay in an intensive care unit by using a computerized data collection system . Verified values falling outside threshold limits were analyzed according to insult grade and duration with the aid of logistic regression . A decision tree was automatically produced from root node to target classes ( Glasgow Outcome Scale [ GOS ] score ) . Among 69 patients , in whom eight insult categories could be assessed , outcome at 12 months was analyzed using logistic regression to determine the relative influence of patient age , admission Glasgow Coma Scale score , Injury Severity Score ( ISS ) , pupillary response on admission , and insult duration . The most significant predictors of mortality in this patient set were duration of hypotensive , pyrexic , and hypoxemic insults . When good and poor outcomes were compared , hypotensive insults and pupillary response on admission were significant . Using decision tree analysis , the authors found that hypotension and low cerebral perfusion pressure ( CPP ) are the best predictors of death , with a 9.2 % improvement in predictive accuracy ( PA ) over that obtained by simply predicting the largest outcome category as the outcome for each patient . Hypotension was a significant predictor of poor outcome ( GOS Score 1 - 3 ) . Low CPP , patient age , hypocarbia , and pupillary response were also good predictors of outcome ( good/poor ) , with a 5.1 % improvement in PA . In certain subgroups of patients pyrexia was a predictor of good outcome . CONCLUSIONS Decision tree analysis confirmed some of the results of logistic regression and challenged others . This investigation shows that there is knowledge to be gained from analyzing observational data with the aid of decision tree analysis Outcome following traumatic brain injury ( TBI ) is not only dependent on the nature and severity of injury and subsequent treatment , but also on constituent characteristics of injured individuals . We aim ed to describe and quantify the relationship between demographic characteristics and six month outcome assessed by the Glasgow Outcome Scale ( GOS ) after TBI . Individual patient data on age ( n = 8719 ) , gender ( n = 8720 ) , race ( n = 5320 ) , and education ( n = 2201 ) were extracted from eight therapeutic Phase III r and omized clinical trials and three surveys in moderate or severe TBI , contained in the IMPACT data base . The strength of prognostic effects was analyzed with binary and proportional odds regression analysis and expressed as an odds ratio . Age was analyzed as a continuous variable with spline functions , and the odds ratio calculated over the difference between the 75 th and 25 th percentiles . Associations with other predictors were explored . Increasing age was strongly related to poorer outcome ( OR 2.14 ; 95 % CI 2.00 - 2.28 ) in a continuous fashion that could be approximated by a linear function . No gender differences in outcome were found ( OR : 1.01 ; CI 0.92 - 1.11 ) , and exploratory analysis failed to show any gender/age interaction . The studies included predominantly Caucasians ( 83 % ) ; outcome in black patients was poorer relative to this group ( OR 1.30 ; CI 1.09 - 1.56 ) . This relationship was sustained on adjusted analyses , and requires further study into mediating factors . Higher levels of education were weakly related to a better outcome ( OR : 0.70 ; CI 0.52 - 0.94 ) . On multivariable analysis adjusting for age , motor score , and pupils , the prognostic effect of race and education were sustained . We conclude that outcome following TBI is dependent on age , race , to a lesser extent on education , but not on gender We determined the relationship between secondary insults ( hypoxia , hypotension , and hypothermia ) occurring prior to or on admission to hospital and 6-month outcome after traumatic brain injury ( TBI ) . A meta- analysis of individual patient data , from seven Phase III r and omized clinical trials ( RCT ) in moderate or severe TBI and three TBI population -based series , was performed to model outcome as measured by the Glasgow Outcome Scale ( GOS ) . Proportional odds modeling was used to relate the probability of a poor outcome to hypoxia ( N = 5661 ) , hypotension ( N = 6629 ) , and hypothermia ( N = 4195 ) separately . We additionally analyzed the combined effects of hypoxia and hypotension and performed exploratory analysis of associations with computerized tomography ( CT ) classification and month of injury . Having a pre-enrollment insult of hypoxia , hypotension or hypothermia is strongly associated with a poorer outcome ( odds ratios of 2.1 95 % CI [ 1.7 - 2.6 ] , 2.7 95 % CI [ 2.1 - 3.4 ] , and 2.2 95 % CI [ 1.6 - 3.2 ] , respectively ) . Patients with both hypoxia and hypotension had poorer outcomes than those with either insult alone . Radiological signs of raised intracranial pressure ( CT class III or IV ) were more frequent in patients who had sustained hypoxia or hypotension . A significant association was observed between month of injury and hypothermia . The occurrence of secondary insults prior to or on admission to hospital in TBI patients is strongly related to poorer outcome and should therefore be a priority for emergency department personnel Objective To introduce the electroencephalogram silence-ratio ( ESR ) as a variable derived from mathematically processed electroencephalogram for early outcome prognosis in patients with severe head trauma and to comparatively assess sensitivity , specificity and predictive value vs. somatosensory evoked potentials and brainstem auditory evoked potentials . Design Prospect i ve , interventional study . Setting Intensive care unit of a university hospital . Patients A total of 32 adults with severe acute head trauma ( Glasgow Coma Scale score ≤8 ) . Methods and Main Results In all patients , electroencephalographic recording was continuously performed by frontomastoid electrode montage for 24–96 hrs after admission to the ICU . The data were subsequently computed by fast Fourier analysis and the ESR ( intervals of suppression as periods > 240 msecs during which the electroencephalographic voltage did not exceed 5 & mgr;V ) was displayed and recorded on a computer for further evaluation . Somatosensory evoked potentials and brainstem auditory evoked potentials were elicited during the first 2 days after admission . Outcome evaluation was performed 6 months after trauma using the Glasgow Outcome Scale and the Rappaport Disability Rating Scale . After careful artifact exclusion , the ESR depicted the highest sensitivity , specificity , and positive predictive value compared with evoked potentials . Even a highly significant correlation between outcome and ESR was found ( p < .0001 ) . Conclusion The ESR is a valuable variable showing a high reliability with respect to outcome prediction in severe head trauma with a higher predictive value than short latency somatosensory evoked potentials . Evidence exists that the ESR provides at least partial information regarding adequate cerebral oxygen delivery We aim ed to describe and quantify the relationship between cause of injury and final outcome following traumatic brain injury ( TBI ) . Individual patient data ( N = 8708 ) from eight therapeutic Phase III r and omized clinical trials in moderate or severe TBI , and three TBI surveys were used to investigate the relationship between cause of injury and outcome , as assessed by the Glasgow Outcome Scale ( GOS ) at 6 months . Proportional odds methodology was applied to quantify the strength of the association and expressed as an odds ratio in a meta- analysis . Heterogeneity across studies was assessed and associations with other predictive factors explored . In a univariate analysis , a strong association between the cause of injury and long-term outcome in moderate to severe TBI patients was observed , with consistent results across the studies . Road traffic accidents ( OR 0.66 , 95 % CI 0.60 - 0.73 ) , assaults ( OR 0.66 , 95 % CI 0.52 - 0.84 ) , and injuries sustained during sporting or recreational activities ( OR 0.45 , 95 % CI 0.28 - 0.71 ) were all associated with better outcomes than the reference category of falls . Falls were found to be associated with an older age and with a higher incidence of mass lesions . Following adjustment for age in the analysis , the relationship between cause of injury and outcome was lost Jugular bulb oxygen monitoring can be used to estimate the adequacy of cerebral blood flow to support cerebral metabolism after severe head injury . In the present study , the authors studied the cerebral arteriovenous oxygen difference ( AVDO[2 ] ) before and after treatment in 32 head-injured patients ( Glasgow Coma Scale scores < or = 8) to examine the relationships among AVDO and cerebral perfusion pressure ( CPP ) , delayed cerebral infa rct ion , and outcome . Fifteen patients ( Group A ) underwent craniotomy for hematoma evacuation and 17 ( Group B ) received mannitol for sustained intracranial hypertension ( intracranial pressure > 20 mm Hg , > 10 minutes ) . Radiographic evidence of delayed cerebral infa rct ion was observed in 14 patients . Overall , 17 patients died or were severely disabled . Cerebral AVDO(2 ) was elevated before craniotomy or mannitol administration ; the mean AVDO(2 ) for all patients before treatment was 8.6 + /- 1.8 vol% . Following craniotomy or mannitol administration , the AVDO(2 ) decreased in 27 patients and increased in five patients ( mean AVDO(2 ) 6.2 + /- 2.1 vol% in all patients ; 6 + /- 1.9 vol% in Group A ; and 6.4 + /- 2.4 vol% in Group B ) . The mean CPP was 75 + /- 9.8 mm Hg and no relationship with AVDO(2 ) was demonstrated . Before treatment , the AVDO(2 ) was not associated with delayed cerebral infa rct ion or outcome . By contrast , a limited improvement in elevated AVDO(2 ) after craniotomy or mannitol administration was significantly associated with delayed cerebral infa rct ion ( Group A : p < 0.001 ; Group B : p < 0.01 ) . Similarly , a limited improvement in elevated AVDO(2 ) after treatment was significantly associated with an unfavorable outcome ( Group A : p < 0.01 ; Group B : p < 0.001 ) . In conclusion , these findings strongly indicate that , despite adequate cerebral perfusion , limited improvement in elevated cerebral AVDO(2 ) after treatment consisting of either craniotomy or mannitol administration may be used to help predict delayed cerebral infa rct ion and poor outcome after traumatic brain injury Using a structured outcome interview , this study addressed the validity and sensitivity to change of the Glasgow Outcome Scale ( GOS ) and the Extended GOS ( GOSE ) in a prospect i ve study of patients who sustained mild ( n = 30 ) to moderate ( n = 13 ) traumatic brain injury ( TBI ) or general trauma ( n = 44 ) . The patients were recruited from the emergency center or inpatient units of Ben Taub General Hospital and invited to participate in follow-up examinations at 3 and 6 months . Using a series of functional outcome measures , assessment of affective status , and neuropsychological tests as criteria , the validity of the GOSE generally exceeded the GOS . Analysis of the outcome data for the patients who completed both the 3-month and 6-month assessment s disclosed that the GOSE was more sensitive to change than the GOS . Comparison of the 3-month outcome data disclosed that the GOSE and GOS scores did not differ for the TBI and general trauma groups . These findings lend further support for utilization of the GOSE in clinical trials when it is based on a structured interview OBJECTIVE To evaluate the course and identify determinants of community integration for up to 3 years following moderate to severe traumatic brain injury . DESIGN Prospect i ve cohort study . PATIENTS A total of 119 moderate to severe traumatic brain injury patients aged 16 - 67 years . METHODS The Community Integration Question naire was completed at 3 , 6 , 12 , 18 , 24 and 36 months post-injury . Repeated measures analysis of variance was performed to determine changes over time in the Community Integration Question naire and its subscales . Bivariate and multivariate regression analyses were used to identify determinants of community integration 36 months post-injury . RESULTS Compared with pre-injury , mean home integration , social integration , productivity , and total question naire scores decreased 3 months post-injury . Patient scores showed maximal improvement during the first year post -- injury . Mean home integration , productivity , and total scores increased to a lesser extent during years 1 - 3 post-injury . Age , Barthel Index scores , hospital discharge destination , and pre-injury community integration scores were the major determinants of community integration 36 months post-injury ( R2 = 60 % ) . CONCLUSION After an initial decline , mean community integration scores gradually improve following moderate to severe traumatic brain injury . Underst and ing the course and determinants of community integration is necessary in order to determine functional prognosis following traumatic brain injury BACKGROUND Head injury is associated with increased blood levels of catecholamines and cortisol . Catecholamines release neutrophil stores , and corticosteroids cause a decrease in the egress of neutrophils from the circulation . The acute-phase response is also characterized by a leukocytosis upon admission . Therefore , it is possible that an increase in the white blood cell ( WBC ) count might serve as an additional diagnostic and prognostic indicator in head injury . METHODS We prospect ively studied 624 patients with severe , moderate , or minor head injury who were admitted to the neurosurgical department of Asclepeion Hospital in Athens between December 1997 and March 1999 . In all cases , WBC count was obtained on admission to the emergency department . Factors that might influence WBC were excluded from this study . RESULTS Patients with severe head injury had significantly higher white blood cell counts than did those with moderate or minor injury ( p < 0.001 ) . Among the patients with severe head injury , a significant relationship was found between WBC counts and Glasgow Coma Scale score , pupillary reaction , and presence of subarachnoid hemorrhage ( p < 0.001 ) . In the same group of patients , WBC counts were significantly higher in those with an unfavorable outcome ( p < 0.001 ) . Multivariate analysis also showed that WBC counts were an independent predictor of outcome . CONCLUSIONS WBC counts on admission could serve as a significant parameter of severity of injury and as an additional predictor of neurological outcome in patients with severe head injury Objectives To study the occurrence of secondary insults and the influence of extracranial injuries on cerebral oxygenation and outcome in patients with closed severe head injury ( Glasgow Coma Scale score ≤8 ) . Design Two-year prospect i ve , clinical study . Setting Two intensive care units in a level III trauma center . Patients We studied 119 patients . Eighty patients had severe head injury and were divided into two categories : “ isolated ” severe head injury patients ( n = 36 , Injury Severity Score < 30 ) , and severe head injury patients with associated extracranial injuries ( n = 44 , Injury Severity Score > 29 ) . Thirty-nine patients with extracranial injuries and no head injury served as the control group . Interventions After patients were admitted to the intensive care unit , we began continuous multimodal cerebral monitoring of intracranial pressure , mean arterial blood pressure , cerebral perfusion pressure , end-tidal Co2 , brain tissue Po2 ( Licox ) , jugular bulb oxyhemoglobin saturation in severe head injury patients , and mean arterial blood pressure in the control group . Targets of management included intracranial pressure < 20 mm Hg , cerebral perfusion pressure > 60 mm Hg , Paco2 > 30 mm Hg , control of cerebral oxygenation , and delayed surgery for non-life-threatening extracranial lesions . Measurements and Main Results Data were analyzed for critical thresholds . The occurrence of secondary insults ( intracranial pressure > 20 mm Hg , mean arterial blood pressure < 70 mm Hg , cerebral perfusion pressure < 60 mm Hg , end-tidal Co2 < 30 torr , brain tissue Po2 < 10 torr , jugular bulb oxyhemoglobin saturation < 50 % ) was comparable in patients with isolated severe head injury and those with severe head injury with associated extracranial lesions ( Abbreviated Injury Scale score ≤5 ) . The duration of intracranial hypertension and arterial hypotension significantly correlated with an unfavorable outcome , independent of the Injury Severity Score . In patients with severe head injury , 1-yr outcome was 29 % dead or vegetative , 17 % severely disabled , and 54 % moderate or good outcome . This was similar to patients with severe head injury and extracranial injuries ( 31 % dead or vegetative , 14 % severely disabled , and 56 % moderate or good outcome ) and was independent of the Injury Severity Score . Patients with no head injury had less secondary insults ( mean arterial blood pressure < 70 mm Hg , p < .01 ) and a better outcome compared with both severe head injury groups ( p < .044 ) . Conclusions In patients with severe head injury who have targeted management including intracranial pressure- and cerebral perfusion pressure-guided therapy and delayed surgery for extracranial lesions , the occurrence of secondary insults in the intensive care unit and long-term neurological outcome were comparable and independent of the presence of extracranial lesions ( Abbreviated Injury Severity level ≤5 ) . A severe head injury is still a major contributor predicting an unfavorable outcome in multiply injured patients We studied the prognostic value of a wide range of conventional and novel prognostic factors on admission after traumatic brain injury ( TBI ) using both univariate and multivariable analysis . The outcome measure was Glasgow Outcome Scale at 6 months after injury . Individual patient data were available on a cohort of 8686 patients drawn from eight r and omized controlled trials and three observational studies . The most powerful independent prognostic variables were age , Glasgow Coma Scale ( GCS ) motor score , pupil response , and computerized tomography ( CT ) characteristics , including the Marshall CT classification and traumatic subarachnoid hemorrhage . Prothrombin time was also identified as a powerful independent prognostic factor , but it was only available for a limited number of patients coming from three of the relevant studies . Other important prognostic factors included hypotension , hypoxia , the eye and verbal components of the GCS , glucose , platelets , and hemoglobin . These results on prognostic factors will underpin future work on the IMPACT project , which is focused on the development of novel approaches to the design and analysis of clinical trials in TBI . In addition , the results provide pointers to future research , including further analysis of the prognostic value of prothrombin time , and the evaluation of the clinical impact of intervening aggressively to correct abnormalities in hemoglobin , glucose , and coagulation Continuous electroencephalography ( cEEG ) is potentially useful in determining prognosis in patients with traumatic brain injuries ( TBI ) . The objective of this prospect i ve , observational cohort study was to determine if the percent alpha variability ( PAV ) on cEEG was predictive of outcome following TBI . Injury characteristics were indexed to assess whether lesions in specific cerebral loci were correlated with PAV and patient recovery . Fifty-three TBI patients were studied using cEEG recording and serial neuroimaging . Clinical recovery was assessed at regular intervals in hospital and following discharge . The principal outcome measures included the mean 3-day PAV score , the 7-day PAV pattern , delineation of the anatomical sites of brain injury , and the 6-month clinical outcome , as measured by the Glasgow Outcome Scale ( GOS ) . Significant univariate ( p = 0.030 ) and multivariate ( p = 0.008 ) relations were identified between PAV and GOS scores . PAV offered good discrimination between favorable and unfavorable 6-month outcomes ( AUC 0.76 ) and , with a cutpoint of 0.20 , had a sensitivity of 87 % and negative predictive value of 82 % . Multivariate modeling revealed that injuries of the thalamus ( p = 0.009 ) and basal ganglia ( p = 0.016 ) , and the presence of diffuse edema ( p = 0.009 ) , were the key anatomical predictors of PAV . Brainstem injuries ( p = 0.020 ) and indicators of diffuse cerebral trauma , such as deep white matter shearing ( p = 0.036 ) and multiple subcortical lesions ( p = 0.033 ) , were the principal determinants of 6-month recovery . Inclusion of PAV enhanced the accuracy of prediction models that encompassed a selective combination of clinical and anatomical variables ( adjusted R(2 ) = 0.458 , p < 0.001 ) . The two main results of this study are ( 1 ) PAV is a sensitive predictor of 6-month clinical outcomes following TBI , and ( 2 ) injury to the thalamus is related to impaired PAV . PAV appears best utilized as a functional adjunct to traditional clinical and anatomical predictors OBJECTIVE Accurate and consistent outcome assessment is essential to r and omized clinical trials . We aim ed to explore observer variation in the assessment of outcome in a recently completed trial of dexanabinol in head injury and to consider steps to reduce such variation . METHODS Eight hundred sixty-one patients with severe traumatic brain injury who were admitted to 86 centers were included in a multicenter , placebo-controlled , Phase III trial . Outcome was assessed at 3 and 6 months postinjury using the extended Glasgow Outcome Scale ; st and ardized assessment was facilitated by the use of a structured interview . Before initiation of trial centers , outcome ratings were obtained for sample cases to establish initial levels of agreement . Training sessions in outcome assessment were held , and problems in assigning outcome were investigated . During the trial , a process of central review was established to monitor performance . Interobserver variation was analyzed using the κ statistic . RESULTS Substantial observer variation was found in the rating of sample cases ( weighted κ , 0.72 ; confidence interval , 0.68–0.75 ) and in assigning outcome based on completed structured interviews ( weighted κ , 0.61 ; confidence interval , 0.57–0.64 ) . In the early stages of the trial , a relatively large number of discrepancies ( 29–37 % ) were identified on central review . This number declined as the trial progressed and coincided with investigator training and feedback from central review . Centers with higher enrollment rates showed better performance . CONCLUSION Observer variation in outcome assessment is a significant problem for head injury trials . Consistency can be improved by st and ardizing procedures , training assessors , and monitoring the quality of assessment s and providing feedback to interviewers OBJECTIVES The goal of this study was to demonstrate the posttraumatic neurochemical damage in normal-appearing brain and to assess mitochondrial dysfunction by measuring N-acetylaspartate ( NAA ) levels in patients with severe head injuries , using proton ( 1H ) magnetic resonance ( MR ) spectroscopy . METHODS Semiquantitative analysis of NAA relative to creatine-containing compounds ( Cr ) and choline ( Cho ) was carried out from proton spectra obtained by means of chemical shift ( CS ) imaging and single-voxel ( SV ) methods in 25 patients with severe traumatic brain injuries ( TBIs ) ( Glasgow Coma Scale scores < or = 8) using a 1.5-tesla MR unit . Proton MR spectroscopy was also performed in 5 healthy volunteers ( controls ) . RESULTS The SV studies in patients with diffuse TBI showed partial reduction of NAA/Cho and NAA/Cr ratios within the first 10 days after injury ( means + /- st and ard deviations 1.59 + /- 0.46 and 1.44 + /- 0.21 , respectively , in the patients compared with 2.08 + /- 0.26 and 2.04 + /- 0.31 , respectively , in the controls ; nonsignificant difference ) . The ratios gradually declined in all patients as time from injury increased ( mean minimum values NAA/Cho 1.05 + /- 0.44 and NAA/Cr 1.05 + /- 0.30 , p < 0.03 and p < 0.02 , respectively ) . This reduction was greater in patients with less favorable outcomes . In patients with focal injuries , the periphery of the lesions revealed identical trends of NAA/Cho and NAA/Cr decrease . These reductions correlated with outcome at 6 months ( p < 0.01 ) . Assessment with multivoxel methods ( CS imaging ) demonstrated that , in diffuse injury , NAA levels declined uniformly throughout the brain . At 40 days postinjury , initially low NAA/Cho levels had recovered to near baseline in patients who had good outcomes , whereas no recovery was evident in patients with poor outcomes ( p < 0.01 ) . CONCLUSIONS Using (1)H-MR spectroscopy , it is possible to detect the posttraumatic neurochemical damage of the injured brain when conventional neuroimaging techniques reveal no abnormality . Reduction of NAA levels is a dynamic process , evolving over time , decreasing and remaining low throughout the involved tissue in patients with poor outcomes . Recovery of NAA levels in patients with favorable outcomes suggests marginal mitochondrial impairment and possible re synthesis from vital neurons This paper describes the pilot phase of the National Traumatic Coma Data Bank , a cooperative effort of six clinical head-injury centers in the United States . Data were collected on 581 hospitalized patients with severe non-penetrating traumatic head injury . Severe head injury was defined on the basis of a Glasgow Coma Scale ( GCS ) score of 8 or less following nonsurgical resuscitation or deterioration to a GCS score of 8 or less within 48 hours after head injury . A common data collection protocol , definitions , and data collection instruments were developed and put into use by all centers commencing in June , 1979 . Extensive information was collected on pre-hospital , emergency room , intensive care , and recovery phases of patient care . Data were obtained on all patients from the time of injury until the end of the pilot study . The pilot phase of the Data Bank provides data germane to questions of interest to neurosurgeons and to the lay public . Questions are as diverse as : what is the prognosis of severe brain injury ; what is the impact of emergency care ; and what is the role of rehabilitation in the recovery of the severely head-injured patient OBJECT Patients with head injuries traditionally were categorized on the basis of whether their lesions appeared to be diffuse , focal , or mass lesions on admission computerized tomography ( CT ) scanning . In the classification of Marshall , et al. , the presence of a hematoma ( evacuated or not evacuated ) is more significant than any diffuse injury ( DI ) . The CT scan appearance after evacuation of a mass lesion has not been analyzed previously in relation to outcome . The authors have investigated the importance of : 1 ) neurological assessment at hospital admission ; 2 ) the status of the basal cisterns and associated intracranial lesions on the admission CT scan ; and 3 ) the degree of DI on the early CT scan obtained after craniotomy to identify patients at risk for development of raised intracranial pressure ( ICP ) and lowered cerebral perfusion pressure ( CPP ) and to discover the influence of the postoperative CT appearance of the lesion on patient outcome . METHODS The authors prospect ively studied 82 patients with isolated , severe closed head injury ( Glasgow Coma Scale [ GCS ] score < or = 8) , all of whom had intracranial hematoma . Both ICP and CPP were continuously monitored , and a CT scan was obtained within 2 to 12 hours after craniotomy . The CT images were categorized according to the classification of Marshall , et al. The mortality rate during the hospital stay was 37 % , and 50 % of the patients achieved a favorable outcome . Compression of the basal cistern on the admission ( preoperative ) CT scan was associated with raised ICP and a CPP of less than 70 mm Hg but not with any other features or with poor patient outcome . In 53 patients the postoperative CT scan revealed DIs III or IV and 29 patients had DIs I or II . The percentages of time during the hospital stay in which ICP was higher than 20 mm Hg and CPP was lower than 70 mm Hg as well as unfavorable outcome were higher in the group of patients in whom DI III or IV was present ( p < 0.001 ) . Raised ICP , CPP lower than 70 mm Hg , DI III or IV , and unfavorable outcome were more frequently observed in patients who presented with a motor (m)GCS score of 3 or less , bilateral unreactive pupils , associated intracranial injuries , and hypotension ( p < 0.001 ) . When logistic regression analysis was performed , an mGCS score of 3 or less ( p = 0.0013 , odds ratio [ OR ] 10.8 ) , bilateral unreactive pupils ( p = 0.0047 , OR 31.8 ) , and DI III or IV observed on CT scanning after surgery ( p = 0.015 , OR 8.9 ) were independently associated with poor outcome . CONCLUSIONS Features on CT scans obtained shortly after craniotomy constitute an independent predictor of outcome in patients with traumatic hematoma . Patients in whom DI III or IV appears on postoperative CT scanning , who often present with an mGCS score of 3 or less and nonreactive pupils , are at high risk for the development of raised ICP and lowered CPP Lew HL , Dikmen S , Slimp J , Temkin N , Lee EH , Newell D , Robinson LR : Use of somatosensory-evoked potentials and cognitive event-related potentials in predicting outcomes of patients with severe traumatic brain injury . Am J Phys Med Rehabil 2003;82:53–61 . Objective This study was performed to evaluate the usefulness of somatosensory-evoked potentials ( SEPs ) and cognitive event-related potentials ( ERPs ) in predicting functional outcomes of severe traumatic brain injury patients . Design Prospect i ve study of 22 patients with severe traumatic brain injury . Demographic information , Glasgow Coma Scale , and electrophysiologic measurements were recorded . Functional outcomes , as quantified by the Glasgow Outcome Scale – Extended , were obtained . Results Bilateral absence of median nerve SEP was strongly predictive of the worst functional outcome . The specificity and positive predictive value of absent SEP for predicting death or persistent vegetative state at 6 mo after traumatic brain injury were as high as 100 % . If the definition of unfavorable outcome was exp and ed to include Glasgow Outcome Scale – Extended 1–4 , absence of ERP was equivalent to the absence of SEP in specificity and positive predictive value . On the other h and , normal ERPs showed higher sensitivity and negative predictive value for prognosticating the best outcomes compared with normal SEPs . If the definition of favorable outcome was exp and ed to include Glasgow Outcome Scale – Extended 5–8 , ERP was still superior to SEP for prognosticating good outcome . Interestingly , the highest sensitivity and negative predictive value for favorable outcomes were associated with the presence of any discernible waveform . Conclusions Although median nerve SEP continues to make reliable prediction of ominous outcome in severe traumatic brain injury , the addition of the speech-evoked ERPs may be helpful in predicting favorable outcomes . The strength of the latter test seems to complement the weakness of the former |
590 | 21,246,410 | Conclusions Most RCTs of gastric cancer surgery do not include measures of QOL and those that do suffer from important limitations .
RCTs would be more useful to surgeons and patients if authors measured PROs and utilized existing approaches to present the results of PROs in ways that provide an intuitive sense of the magnitude of effects | Background Surgery may have a profound effect on patients ’ health-related quality of life ( QOL ) .
To be optimally useful , trials that seek to guide clinical decision making should measure outcomes that are important to patients and report the results in a clinical ly meaningful way .
We sought to explore how research ers currently measure and interpret QOL in surgical trials , using gastric cancer as a case study . | Objective : Roux-en-Y reconstruction with and without jejunal pouch was compared in a r and omized controlled trial to identify the optimal reconstruction procedure in terms of quality of life . Background Data : R and omized trials comparing techniques of reconstruction after total gastrectomy have shown controversial results . Methods : One hundred and thirty-eight patients with gastric cancer were intraoperatively r and omized for Roux-en-Y reconstruction with pouch ( n = 71 ) or without pouch ( n = 67 ) after gastrectomy and stratified into curative or palliative resection . Intra- and postoperative complications were recorded . Body weight and quality of life were determined every 6 months with a follow-up of up to 12 years . Results : Both groups were comparable for age , sex , incidence of concomitant disease , and staging . There were no differences in operative time , postoperative complications , and mortality . Short- and long-term weight loss was similar in both groups . In the first postoperative year , there were no benefits of pouch reconstruction in terms of quality of life , independent of the resection status . In the third , fourth , and fifth year after surgery quality of life was significantly improved for patients with a pouch . Conclusions : Roux-en-Y pouch reconstruction after gastrectomy is simple to perform and safe . Long-term survivors benefit from pouch reconstruction . Therefore , a pouch is recommended for patients with a good prognosis 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 Quality of life ( QOL ) was studied in gastric cancer patients treated on a r and omised , controlled trial comparing D1 ( level 1 ) with D3 ( levels 1 , 2 and 3 ) lymphadenectomy . A total of 221 patients were r and omly assigned to D1 ( n=110 ) and D3 ( n=111 ) surgery . Quality -of-life assessment s included functional outcomes ( a 14-item survey about treatment-specific symptoms ) and health perception ( Spitzer QOL Index ) was performed before and after surgery at disease-free status . Patients suffered from irrelative events such as loss of partners was excluded thereafter . Main analyses were done by intention-to-treat . Thus , 214 D1 ( 106/110=96.4 % ) and D3 ( 108/111=97.3 % ) R0 patients were assessed . Longitudinal analysis showed that functional outcomes decreased at 6 months after surgery and increased over time thereafter , while health perceptions increased over time in general . On the basis of linear mixed model analyses , patients having total gastrectomy , advanced cancer and hemipancreaticosplenectomy , but not complications had poorer QOL than those without . D1 and D3 patients showed no significant difference in QOL . The results suggest that changes of QOL were largely due to scope of gastric resection , disease status and distal pancreaticosplenectomy , rather than the extent of lymph node dissection . This indicates that nodal dissection can be performed for a potentially curable gastric cancer 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 Objective : During recent years considerable interest has been focused on quality of life as an additional therapeutic outcome measure in the surgical treatment of gastric carcinoma . However , the long term consequences of gastrectomy and the impact on quality of life of different reconstructive techniques are still a matter of controversy . To broaden the criteria for choice of treatment , we conducted a prospect i ve r and omized clinical trial to determine the impact of various gastrectomy procedures on quality of life during a 5-yr follow-up period . Methods : Consecutive patients ( n= 64 ) eligible for curative gastric cancer surgery were r and omized to have either total ( n= 31 ) or subtotal ( n= 13 ) gastrectomy or a jejunal S-shaped pouch ( n= 20 ) as a gastric substitute after total gastrectomy . Assessment s of quality of life were made on seven occasions during a 5-yr period : within 1 wk before surgery , 3 and 12 months after the surgical intervention , and then once/yr . All patients were interviewed by one of two psychiatrists , who rated their symptoms and introduced st and ardized self-report question naires covering both general and specific aspects of life . The raters were blinded for the patients ’ group affiliations . Results : Survival rates were similar in all treatment groups . Patients who had a total gastrectomy continued to suffer from alimentary symptoms , especially indigestion and diarrhea , during the entire follow-up period . However , patients who underwent subtotal gastrectomy had a significantly better outcome already during the first postoperative yr . Patients given a gastric substitute after gastrectomy improved with the passage of time and had an even better outcome in the long run . Conclusions : To optimize the rehabilitation after gastrectomy , patients ’ quality of life must be taken into consideration . When subtotal gastrectomy is clinical ly feasible , this procedure has advantages in the early postoperative period . However , a pouch reconstruction after total gastrectomy should be considered in patients having a favorable tumor status suggesting a fair chance of long term survival Objective : “ Rediscovered ” in 1976 , transhiatal esophagectomy ( THE ) has been applicable in most situations requiring esophageal resection and reconstruction . The objective of this study was to review the authors ’ 30-year experience with THE and changing trends in its use . Methods : Using the authors ’ prospect i ve Esophagectomy Data base , this single institution experience with THE was analyzed retrospectively . Results : Two thous and and seven THEs were performed—1063 ( previously reported ) between 1976 and 1998 ( group I ) and 944 from 1998 to 2006 ( group II ) , 24 % for benign disease , 76 % , cancer . THE was possible in 98 % . Stomach was the esophageal substitute in 97 % . Comparing outcomes between group I and group II , statistically significant differences ( P < 0.001 ) were observed in hospital mortality ( 4 % vs. 1 % ) ; adenocarcinoma histology ( 69 % vs. 86 % ) ; use of neoadjuvant chemoradiation ( 28 % vs. 52 % ) ; mean blood loss ( 677 vs. 368 mL ) ; anastomotic leak ( 14 % vs. 9 % ) ; and discharge within 10 days ( 52 % vs. 78 % ) . Major complications remain infrequent : wound infection/dehiscence , 3 % , atelectasis/pneumonia , 2 % , intrathoracic hemorrhage , recurrent laryngeal nerve paralysis , chylothorax , and tracheal laceration , < 1 % each . Late functional results have been good or excellent in 73 % . Aggressive preoperative conditioning , avoiding the ICU , improved pain management , and early ambulation reduce length of stay , with 50 % in group II discharged within 1 week . Conclusion : THE refinements have reduced the historic morbidity and mortality of esophageal resection . This largest reported THE experience reinforces the value of consistent technique and a clinical pathway in managing these high acuity esophageal patients Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Despite increasing acknowledgment of its importance ( 1 ) , some clinicians continue to characterize evidence -based medicine ( EBM ) as focusing on groups of patients and neglecting the individual ( 2 , 3 ) . In this 2-part editorial , we will describe EBM tools that address individual patient decision-making . In this first part we will focus on guides for applying research evidence and for determining the benefit-to-risk ratio in individual patients . 1 . EBM provides guides for addressing the applicability of r and omized controlled trials to individual patients EBM assists clinicians who ponder how generalizable r and omized controlled trial ( RCT ) results are to their individual patients and their circumstances ( Table ) ( 4 - 6 ) . That guidance directs clinicians to look for possible differences in biological factors , socioeconomic characteristics , and attitudinal or behavioral characteristics of individual patients that might modulate treatment effects ( 7 ) . For instance , antibiotics for otitis media seem to be most beneficial in children < 2 years of age with bilateral acute otitis media and in children with both acute otitis media and otorrhea ( 8) . Health care characteristics should also be considered because research studies are often conducted at specialized centers with capabilities and expertise exceeding those available for routine patient care . This factor is of particular concern when applying the results of trials conducted in high-income setting s to low-income setting s or to trials in which the clinician 's skill is a central aspect of the intervention , such as surgical trials where the average surgeon might not be as skilled or experienced with the procedure as surgeons in the study ( 9 ) . Finally , outcome characteristics should be considered . RCTs focused on surrogate endpoints ( e.g. , bone density rather than fractures ) are less directly applicable to patients than trials focused on patient-important outcomes . Although clinicians should consider these criteria when applying the results of research studies to individual patients , EBM emphasizes that treatment effects are usually sufficiently similar across patients with the same condition to allow application to the individual after patient-specific baseline risk is considered . Table 1 . Criteria to consider when applying the results of research studies to individual patients Patient characteristics Health care characteristics Outcome characteristics Biologic factors ( sex , comorbid conditions , race , age , severity of pathology)Patient compliance with treatment requirements Compliance of health care providers with treatment requirementsRe sources available for implementation ( e.g. , availability of monitoring)Expertise of clinicians Did the study measure an outcome of importance to the individual patient ? 2 . Consideration of individual baseline risk to establish individual benefits and risks In considering the risks and benefits of an intervention to an individual , patients and clinicians will probably find absolute measures ( e.g. , risk difference ) more intuitive and interpretable than relative measures ( e.g. , relative risk ) . The number of patients who would need to be treated to prevent 1 additional adverse event or to create 1 additional beneficial outcome number needed to treat (NNT)is a useful way to characterize the absolute magnitude of a treatment effect ( 10 ) . Although relative measures of effectiveness are similar across patient groups , absolute measures vary depending on the underlying baseline risk . Thus , average risks ( e.g. , difference between control and treatment event rates in an RCT and the corresponding NNT ) are of limited use in individualizing care . What patients want to know is their personal absolute risk reduction , and what clinicians need is the NNT for a group of individuals resembling their patient . EBM offers approaches to establish individual benefits and risks via individual patient expected event rates ( 11 ) . Clinicians can acquire information about baseline risks that are more relevant to individual patients from subgroups of patients in studies on prognosis , epidemiologic studies of incidence of disease , clinical prediction guides ( 12 ) , or RCTs . * Clinicians can use this information to calculate the expected event rate in patients who receive the intervention by multiplying the baseline event rate by the relative risk . Consider this example . A 40-year-old man presenting with an uncomplicated nonST elevation myocardial infa rct ion can expect an absolute risk reduction for dying in the next month of approximately 0.4 % if he received clopidogrel ( baseline risk of 2 % , relative risk reduction 20 % , 2 % 0.2 = 0.4 % ) . This translates into an NNT of 250 ( 100/0.4 ) . The figures for a 70-year-old man presenting with an infa rct ion complicated by heart failure show much greater absolute benefit ( baseline risk 40 % , relative risk reduction 20 % , absolute risk reduction 8 % , NNT 12 to 13 ) . When study data are unavailable , clinicians can use their personal experience and the experience of their colleagues to estimate an individual patient 's baseline risk . Conclusion EBM complements the traditional approach to individualized decision-making ( the clinicians ' instincts ) with a set of rigorous tools and strategies . These include guides to help decide on the applicability of RCTs to the individual and tools to quantify the benefits and risks for the individual in making particular treatment decisions . The process of individualizing care incorporates additional strategies that we will describe in the second part of this editorial The optimal reconstruction protocol aftertotal gastrectomy is still a matter of debate . Pouch reconstructionsare developed to create a larger reservoir for food , to provide abarrier against intestinoesophageal reflux , and to lengthen the foodtransit time . Preservation of the duodenal passage should result inbetter physiologic regulation of the ingested food . Controlledr and omized clinical studies must be conducted to assess the quality oflife after gastrectomy and various types of reconstruction . In thepresent trial , which compared Longmire ’s reconstruction without apouch and Longmire ’s reconstruction with a pouch of varying sizes , weevaluated the quality of life for 41 patients during the firstpostoperative year . The quality of life was examined by an EORTC question naire and an organ-specific module . There were no statisticallyproven benefits for pouch reconstruction in comparison with Longmire’sreconstruction alone . Some benefits are shown for the large pouch butit was only a trend . This is especially so with regard to diarrhea and food consumption . A definitive answer to the question about the valueof a pouch reconstruction after gastrectomy has not yet been attained . It is possible that there will be significant differences betweenreconstruction groups during the long-term follow-up 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 : The purpose of this study was to evaluate the quality of life ( QOL ) after laparoscopy-assisted distal gastrectomy ( LADG ) compared with open distal gastrectomy ( ODG ) in patients with early gastric cancer . Summary Background Data : LADG has been beneficial in terms of pain , recovery , and morbidity when compared with open surgery with equal oncologic outcome . There has been no clinical study on QOL . Methods : From July 2003 to November 2005 , 164 patients with newly diagnosed cT1N0M0 and cT1N1M0 distal gastric cancer were r and omly assigned either to LADG or ODG . All patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 question naires preoperatively and postoperatively on regular follow-up visits . Results : Statistically significant differences were observed with a more favorable outcome noted in the LADG group with respect to intraoperative blood loss ( P < 0.001 ) , total amount of analgesics used ( P = 0.019 ) , the size of the wound ( P < 0.0001 ) , postoperative hospital stay ( P < 0.0001 ) , and QOL parameters of global health ( P < 0.0001 ) . Most of the scales on patient functioning including physical ( P < 0.0005 ) , role ( P = 0.0011 ) , emotional ( P < 0.0001 ) , social ( P < 0.0001 ) , and symptom scales such as fatigue ( P < 0.0001 ) , pain ( P < 0.0001 ) , appetite loss ( P = 0.031 ) , sleep disturbance ( P = 0.003 ) , dysphasia ( P = 0.0024 ) , gastro-esophageal reflux ( P = 0.0127 ) , dietary restriction ( P = 0.0004 ) , anxiety ( P = 0.0036 ) , dry mouth ( P = 0.0007 ) , and body image ( P < 0.0001 ) were also significantly better in the LADG group compared with the ODG group . Conclusions : Comparison of LADG to ODG in patients with early gastric cancer result ed in improved QOL outcomes in the patients followed for up to 3 months in the LADG group BACKGROUND There is increasing evidence that the effect of jejunal pouch reconstruction is satisfactory for reservoir function in several r and omized control studies . However , these studies were performed in patients with advanced gastric cancer , where significant numbers of the patients died of disease recurrence . In order to exclude the influence of disease recurrence , we performed jejunal pouch reconstruction after total gastrectomy in patients with early gastric cancer in a r and omized controlled study and investigated whether or not an improved quality of life ( QOL ) was observed with jejunal pouch reconstruction . METHODS Fifty consecutive patients receiving total gastrectomy for early gastric cancer were prospect ively divided into the Roux-en-Y reconstruction group without pouch ( RY group ) or the jejunal pouch reconstruction group ( pouch group ) . Body weight , eating capacity , QOL assessment by gastrointestinal symptom rating scale ( GSRS ) , nutritional parameters , endoscopical examination , 24-hour pH monitoring and Bilitec monitoring were evaluated at 3 , 12 , and 48 months after surgery . RESULTS Jejunal pouch reconstruction provided the better QOL than Roux-en-Y reconstruction without pouch both at short-term and long-term periods in a r and omized control study . Moreover , as a new finding , pouch reconstruction provided less bile reflux into the esophagus compared with Roux-en-Y reconstruction . CONCLUSIONS Jejunal pouch reconstruction provided improvement of QOL in patients receiving total gastrectomy 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 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 Objective : To evaluate the quality of reporting of surgical r and omized controlled trials published in surgical and general medical journals using Jadad score , allocation concealment , and adherence to CONSORT guidelines and to identify factors associated with good quality . Summary Background Data : R and omized controlled trials ( RCTs ) provide the best evidence about the relative effectiveness of different interventions . Improper methodology and reporting of RCTs can lead to erroneous conclusions about treatment effects , which may mislead decision-making in health care at all levels . Methods : Information was obtained on RCTs published in 6 general surgical and 4 general medical journals in the year 2003 . The quality of reporting of RCTs was assessed under masked conditions using allocation concealment , Jadad score , and a CONSORT checklist devised for the purpose . Results : Of the 69 RCTs analyzed , only 37.7 % had a Jadad score of ≥3 , and only 13 % of the trials clearly explained allocation concealment . The modified CONSORT score of surgical trials reported in medical journals was significantly higher than those reported in surgical journals ( Mann-Whitney U test , P < 0.001 ) . Overall , the modified CONSORT score was higher in studies with higher author numbers ( P = 0.03 ) , multicenter studies ( P = 0.002 ) , and studies with a declared funding source ( P = 0.022 ) . Conclusion : The overall quality of reporting of surgical RCTs was suboptimal . There is a need for improving awareness of the CONSORT statement among authors , review ers , and editors of surgical journals and better quality control measures for trial reporting and methodology BACKGROUND R and omized controlled trials ( RCTs ) in surgery can provide valuable evidence of the efficacy of interventions if they are well- design ed , appropriately executed , and adequately reported . Adequate reporting of methodology in surgical RCTs is known to be poor , and adverse-event reporting in surgical research is inconsistent . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a framework to help authors report their findings in a transparent manner . Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments . The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high- quality surgical journals using the criteria specified in the CONSORT statements . STUDY DESIGN We used impact factor to identify the top three ranked surgical journals in 2004 . We then obtained information on all RCTs published in these journals in the 2005 calendar year . We assessed quality of reporting using Jadad score , compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers , and assessed the number of RCTs adequately reporting key generic method ologic , adverse-event-related , and specific nonpharmacologic criteria . RESULTS Of 42 RCTs analyzed , only 40 % ( 17 of 42 ) had a Jadad score > or = 3 . There was no significant difference in the number of high- quality RCTs published in CONSORT-endorsing journals compared with nonendorsers ( p = 0.3 ) . The median percentage of RCTs adequately reporting generic method ologic , adverse-event-related , and specific nonpharmacologic criteria was 32.5 % , 17 % , and 36.5 % , respectively . CONCLUSIONS Quality of reporting of generic method ologic , adverse-event-related , and specific nonpharmacologic criteria in surgical RCTs is poor . Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria |
591 | 21,856,136 | There was a strong relationship between rectal filling and mesorectal motion .
Current margin recipes may not apply to deformable structures . | Radiotherapy for rectal cancer is becoming more conformal .
Both the rectum and the mesorectum are mobile structures and the use of image-guided radiotherapy techniques may improve treatment delivery .
Studies up to 2008 have previously been review ed ; rectal motion was mostly studied in bladder and prostate cancer cases .
Large variations were seen in both the rectal volume and rectal wall displacement during the treatment course .
We review ed the literature on primary rectal cancer . | PURPOSE To quantify the inter-fraction shape variation of the mesorectum for rectal cancer patients treated with 5 x 5 Gy in supine position and compare it to variation in prone position . METHODS AND MATERIAL S For 28 patients a planning CT ( pCT ) and five daily cone-beam-CT ( CBCT ) scans were acquired in supine position . The mesorectal part of the CTV ( MesoRect ) was delineated on all scans . The shape variation was quantified by the distance between the pCT- and the CBCT delineations and stored in surface maps after online setup correction . Data were analyzed for male and female patients separately and compared to prone data . RESULTS A large range of systematic , 1 - 8 mm ( 1SD ) , and r and om , 1 - 5 mm , shape variation was found , comparable to prone patients . R and om-shape variation was comparable for male and female patients , while systematic variation was 3 mm larger for female patients . CONCLUSIONS Shape variation of the MesoRect is substantial , heterogeneous and different between male and female patients . Differences between supine and prone orientation , however , are small . Clinical margins should be differentiated in position along the cranio-caudal axis , in anterior-posterior direction and for gender . Margins should also be increased , even when online setup correction is used . Due to the small margin differences between prone and supine treatments , the setup choice should be determined on dose to the organs at risk PURPOSE To develop a Radiation Therapy Oncology Group ( RTOG ) atlas of the elective clinical target volume ( CTV ) definitions to be used for planning pelvic intensity-modulated radiotherapy ( IMRT ) for anal and rectal cancers . METHODS AND MATERIAL S The Gastrointestinal Committee of the RTOG established a task group ( the nine physician co- authors ) to develop this atlas . They responded to a question naire concerning three elective CTVs ( CTVA : internal iliac , presacral , and perirectal nodal regions for both anal and rectal case planning ; CTVB : external iliac nodal region for anal case planning and for selected rectal cases ; CTVC : inguinal nodal region for anal case planning and for select rectal cases ) , and to outline these areas on individual computed tomographic images . The imaging files were shared via the Advanced Technology Consortium . A program developed by one of the co- authors ( I.E.N. ) used binomial maximum-likelihood estimates to generate a 95 % group consensus contour . The computer-estimated consensus contours were then review ed by the group and modified to provide a final contouring consensus atlas . RESULTS The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer . The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage . Detailed target volume contouring guidelines and images are discussed . CONCLUSION This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers , as part of prospect i ve RTOG trials Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer . However , improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed . We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy . Methods We undertook a r and omised trial in 80 centres in four countries . 1350 patients with operable adenocarcinoma of the rectum were r and omly assigned , by a minimisation procedure , to short-course preoperative radiotherapy ( 25 Gy in five fractions ; n=674 ) or to initial surgery with selective postoperative chemoradiotherapy ( 45 Gy in 25 fractions with concurrent 5-fluorouracil ) restricted to patients with involvement of the circumferential resection margin ( n=676 ) . The primary outcome measure was local recurrence . Analysis was by intention to treat . This study is registered , number IS RCT N 28785842 . Findings At the time of analysis , which included all participants , 330 patients had died ( 157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy ) , and median follow-up of surviving patients was 4 years . 99 patients had developed local recurrence ( 27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy ) . We noted a reduction of 61 % in the relative risk of local recurrence for patients receiving preoperative radiotherapy ( hazard ratio [ HR ] 0·39 , 95 % CI 0·27–0·58 , p<0·0001 ) , and an absolute difference at 3 years of 6·2 % ( 95 % CI 5·3–7·1 ) ( 4·4 % preoperative radiotherapy vs 10·6 % selective postoperative chemoradiotherapy ) . We recorded a relative improvement in disease-free survival of 24 % for patients receiving preoperative radiotherapy ( HR 0·76 , 95 % CI 0·62–0·94 , p=0·013 ) , and an absolute difference at 3 years of 6·0 % ( 95 % CI 5·3–6·8 ) ( 77·5 % vs 71·5 % ) . Overall survival did not differ between the groups ( HR 0·91 , 95 % CI 0·73–1·13 , p=0·40 ) . Interpretation Taken with results from other r and omised trials , our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada BACKGROUND Postoperative chemoradiotherapy is the recommended st and ard therapy for patients with locally advanced rectal cancer . In recent years , encouraging results with preoperative radiotherapy have been reported . We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy . The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day , five days per week , and fluorouracil , given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy . Surgery was performed six weeks after the completion of chemoradiotherapy . One month after surgery , four five-day cycles of fluorouracil ( 500 mg per square meter per day ) were given . Chemoradiotherapy was identical in the postoperative-treatment group , except for the delivery of a boost of 540 cGy . The primary end point was overall survival . RESULTS Four hundred twenty-one patients were r and omly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy . The overall five-year survival rates were 76 percent and 74 percent , respectively ( P=0.80 ) . The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group ( P=0.006 ) . Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group , as compared with 40 percent of the patients in the postoperative-treatment group ( P=0.001 ) ; the corresponding rates of long-term toxic effects were 14 percent and 24 percent , respectively ( P=0.01 ) . CONCLUSIONS Preoperative chemoradiotherapy , as compared with postoperative chemoradiotherapy , improved local control and was associated with reduced toxicity but did not improve overall survival PURPOSE To determine the reduction of prostate motion during a typical radiotherapy ( RT ) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia . METHODS AND MATERIAL S Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device . The MRIs were at baseline without bowel regimen ( MRI-BL ) , before CT planning with bowel regimen ( MRI-CT ) , and before a r and omly assigned RT fraction ( 1 - 42 ) with bowel regimen ( MRI-RT ) . A single observer tracked displacement of the posterior midpoint ( PM ) of the prostate . The primary endpoints were comparisons of the proportion of time that the PM was displaced > 3 mm ( PTPM3 ) from its initial position , and the secondary endpoints were comparisons of the reduction of initial rectal area , with and without the bowel regimen . RESULTS The mean rectal area was : 13.5 cm(2 ) at MRI-BL , 12.7 cm(2 ) at MRI-CT , and 12.3 cm(2 ) at MRI-RT ( MRI-BL vs. MRI-CT , p = 0.11 ; MRI-BL vs. MRI-CT , p = 0.07 ) . Moving rectal gas alone ( 56 % ) and moving gas and stool ( 18 % ) caused 74 % of intrafraction prostate motion . The PTPM3 was 11.3 % at MRI-BL , 4.8 % at MRI-CT , and 12.0 % at MRI-RT ( MRI-BL vs. MRI-CT , p = 0.12 ; MRI-BL vs. MRI-RT , p = 0.89 ) . CONCLUSION For subjects voiding their rectum before imaging , an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion Background and Purpose : In locally advanced rectal cancer , neoadjuvant radiochemotherapy is indicated . To improve target volume definition for radiotherapy planning , the potential of implanted gold markers in the tumor region was evaluated . Patients and Methods : In nine consecutive patients , two to three gold markers were implanted in the tumor region during rigid rectoscopy . Computed tomography scans were performed during treatment planning . All electronic portal imaging devices ( EPIDs ) recorded during treatment series were analyzed . All patients underwent complete tumor resection with meticulous histopathologic examination . Results : The gold markers could easily be implanted into the mesorectal tissue at the caudal tumor border without any complications . They were helpful in identifying the inferior border of the planning target volume in order to spare normal tissue ( in particular anal structures ) . No significant shift of the markers was found during the course of therapy . Marker matching of the EPIDs did not improve patient positioning in comparison to bone structure matching . The former position of at least one marker could be identified in all patients during histopathologic examination . Conclusion : The use of gold marker enables a more precise definition of the target volume for radiotherapy in patients with rectal cancer . This could eventually allow a better protection of anal structures of patients with a tumor localization ≥ 5 cm cranial of the anal sphincter . The implantation of the gold markers improved communication between the surgeon , the radiooncologist and the pathologist result ing in intensified exchange of relevant informations . Hintergrund und Ziel : Bei Patienten mit fortgeschrittenem Rektumkarzinom ist eine neoadjuvante Radiochemotherapie indiziert . Um die Definition des Zielvolumens zu verbessern , wurde das Potential von implantierten Goldmarkern in der Tumorregion untersucht . Patienten und Method ik : Bei neun konsekutiven Patienten wurden während der prätherapeutischen starren Rektoskopie zwei bis drei Goldmarker in die Tumorregion implantiert . Für die Bestrahlungsplanung wurden computertomographische Bilder aufgenommen . Alle während der Bestrahlung aufgenommenen Portal-Image-Bilder wurden analysiert . Alle Patienten erhielten eine komplette Tumorresektion mit anschließender histopathologischer Untersuchung . Ergebnisse : Die Goldmarker konnten einfach und komplikationslos in das mesorektale Gewebe am kaudalen Tumorr and gelegt werden . Sie waren hilfreich bei der Identifikation des unteren Tumorr and s während der Bestrahlungsplanung , um Normalgewebe ( insbesondere die analen Strukturen ) bei der Bestrahlung schonen zu können . Es f and sich keine signifikante Verschiebung der absoluten Markerpositionen während der Bestrahlung . Eine Korrektur der Lagerung der Patienten nach Markern ergab keinen Vorteil gegenüber der Korrektur mit knöchernen L and marken . Die ehemalige Position von mindestens einem Marker konnte bei jedem Patienten in der histopathologischen Untersuchung bestimmt werden . Schlussfolgerung : Die Verwendung von Goldmarkern bei Patienten mit Rektumkarzinom ermöglicht eine präzisere Definition der Zielvolumens für die Bestrahlungsplanung . Dadurch könnten evtl . anale Strukturen bei einer Tumorlage von ≥ 5 cm kranial des Analsphinkters geschont werden . Die Implantation von Goldmarkern verbessert die Kommunikation zwischen Chirurgen , Radioonkologen und Pathologen , was in einem intensivierten Austausch relevanter Informationen result iert Purpose To compare target dose distribution , comformality , normal tissue avoidance , and irradiated body volume ( IBV ) in 3DCRT using classic anatomical l and marks ( c3DCRT ) , 3DCRT fitting the PTV ( f3DCRT ) , and intensity-modulated radiation therapy ( IMRT ) in patients with locally advanced rectal cancer ( LARC ) . Material s and methods Fifteen patients with LARC underwent c3DCRT , f3DCRT , and IMRT planning . Target definition followed the recommendations of the ICRU reports No. 50 and 62 . OAR ( SB and bladder ) constraints were D5 ≤ 50 Gy and Dmax < 55 Gy . PTV dose prescription was defined as PTV95 ≥ 45 Gy and PTVmin ≥ 35 Gy . Target coverage was evaluated with the D95 , Dmin , and Dmax . Target dose distribution and comformality was evaluated with the homogeneity indices ( HI ) and Conformity Index ( CI ) . Normal tissue avoidance of OAR was evaluated with the D5 and V40 . IBV at 5 Gy ( V5 ) , 10 Gy ( V10 ) , and 20 Gy ( V20 ) were calculated . Results The mean GTV95 , CTV95 , and PTV95 doses were significantly lower for IMRT plans . Target dose distribution was more inhomogeneous after IMRT planning and 3DCRTplans had significantly lower CI . The V40 and D5 values for OAR were significantly reduced in the IMRT plans .V5 was greater for IMRT than for f3DCRT planning ( p < 0.05 ) and V20 was smaller for IMRT plans(p < 0.05 ) . Conclusions IMRT planning improves target conformity and decreases irradiation of the OAR at the expense of increased target heterogeneity . IMRT planning increases the IBV at 5 Gy or less but decreases the IBV at 20 Gy or more PURPOSE To evaluate the influence of a dietary protocol on cone beam computed tomography ( CBCT ) image quality , which is an indirect indicator for short-term ( intrafraction ) prostate motion , and on interfraction motion . Image quality is affected by motion ( e.g. , moving gas ) during imaging and influences the performance of automatic prostate localization on CBCT scans . METHODS AND MATERIAL S Twenty-six patients ( 336 CBCT scans ) followed the dietary protocol and 23 patients ( 240 CBCT scans ) did not . Prostates were automatically localized by using three dimensional ( 3D ) gray-value registration ( GR ) . Feces and ( moving ) gas occurrence in the CBCT scans , the success rate of 3D-GR , and the statistics of prostate motion data were assessed . RESULTS Feces , gas , and moving gas significantly decreased from 55 % , 61 % , and 43 % of scans in the nondiet group to 31 % , 47 % , and 28 % in the diet group ( all p < 0.001 ) . Since there is a known relation between gas and short-term prostate motion , intrafraction prostate motion probably also decreased . The success rate of 3D-GR improved from 83 % to 94 % ( p < 0.001 ) . A decrease in r and om interfraction prostate motion also was found , which was not significant after Bonferroni 's correction . Significant deviations from planning CT position for rotations around the left-right axis were found in both groups . CONCLUSIONS The dietary protocol significantly decreased the incidence of feces and ( moving ) gas . As a result , CBCT image quality and the success rate of 3D-GR significantly increased . A trend exists that r and om interfraction prostate motion decreases . Using a dietary protocol therefore is advisable , also without CBCT-based image guidance AIMS Uncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer . Systematic review s and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000 , respectively . The systematic review s were up date d and revised and new recommendations for preoperative and postoperative therapy were developed based on the up date d body of evidence . The following research questions were addressed : After appropriate preoperative staging tests , should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy ( with or without chemotherapy ) ? What is the role of postoperative radiotherapy and /or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy , in terms of improving survival and delaying local recurrence ? MATERIAL S AND METHODS The MEDLINE , EMBASE and Cochrane Library data bases , as well as meeting proceedings from the American Society of Clinical Oncology , were search ed for reports of r and omised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer . The draft practice guideline and systematic review s were distributed through a mailed survey to 129 health care providers in Ontario for review . RESULTS Systematic review s on preoperative and postoperative therapy for rectal cancer were developed . On the basis of the evidence contained in these review s , the Gastrointestinal Cancer Disease Site Group drafted recommendations . Of the 33 practitioners who responded to the mailed survey , 97 % agreed with the draft recommendations as stated , 88 % agreed that the report should be approved as a practice guideline and 94 % indicated that they were likely to use the guideline in their own practice . CONCLUSIONS Preoperative chemoradiotherapy is preferred , compared with st and ard fractionation preoperative radiotherapy alone , to decrease local recurrence . Preoperative chemoradiotherapy is also preferred , compared with a postoperative approach , to decrease local recurrence and adverse effects . For patients with relative contraindications to chemotherapy in the preoperative period , an acceptable alternative is preoperative radiotherapy alone followed by surgery . Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy PURPOSE To investigate whether a large rectum filling visible on the planning CT scan was associated with a decrease in freedom from any failure ( FFF ) and freedom from clinical failure ( FFCF ) for prostate cancer patients . METHODS AND MATERIAL S Patients from the Dutch trial ( 78 Gy vs. 68 Gy ) with available acute toxicity data were analyzed ( n = 549 ) . A 10-mm margin was applied for the first 68 Gy and 0 - 5 mm for the 10-Gy boost . The dose in the seminal vesicles ( SVs ) was prescribed within four treatment groups according to the estimated risk of SV involvement . Two potential risk factors ( RFs ) for a geometric miss were defined : ( 1 ) an anorectal volume > or = 90 cm(3 ) and > or = 25 % of treatment-time diarrhea ( RF1 ) ; and ( 2 ) the mean cross-sectional area of the anorectum ( RF2 ) . We tested whether these were significant predictors for FFF and FFCF within each treatment group . RESULTS Significant results were observed only for patients with a risk of SV involvement > 25 % ( dose of 68 - 78 Gy to the SVs , n = 349 ) . We found a decrease in FFF ( p = 0.001 ) and FFCF ( p = 0.01 ) for the 87 patients with RF1 ( for RF2 , p = 0.02 and p = 0.01 , respectively ) . The estimated decrease in the FFCF rate at 5 years was 15 % . CONCLUSION Tumor control was significantly decreased in patients with a risk of SV involvement > 25 % and at risk of geometric miss . Current image guidance techniques offer several solutions to geometrically optimize the treatment . Additional research is needed to evaluate whether geometric misses can be prevented using these techniques PURPOSE To study the impact on nodal coverage and dose to fixed organs at risk when using daily fiducial localization of the prostate to deliver intensity-modulated radiotherapy ( IMRT ) . METHODS AND MATERIAL S Five patients with prostate cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied . Dose was prescribed such that 95 % of the prostate planning target volume ( PTV ) and 90 % of the nodal PTV were covered . R and om and systematic prostate displacements in the anterior-posterior , superior-inferior , and left-right directions were simulated to shift the original isocenter of the IMRT plan . The composite dose during the course of treatment was calculated . RESULTS Compared with a static setup , simulating r and om shifts reduced dose by less than 1.5 % for nodal hotspot ( i.e. , dose to 1 cm(3 ) ) , by less than 1 % for the 90 % nodal PTV coverage , and by less than 0.5 % for the nodal mean dose . Bowel and femoral head hotspots were reduced by less than 1.5 % and 2 % , respectively . A 10-mm systematic offset reduced nodal coverage by up to 10 % . CONCLUSION The use of prostate fiducials for daily localization during IMRT treatment results in negligible changes in dose coverage of pelvic nodes or normal tissue sparing in the absence of a significant systematic offset . This offers a simple and practical solution to the problem of image-guided radiotherapy for prostate cancer when including pelvic nodes BACKGROUND Preoperative radiotherapy is recommended for selected patients with rectal cancer . We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy , preoperative chemoradiotherapy , preoperative radiotherapy and postoperative chemotherapy , or preoperative chemoradiotherapy and postoperative chemotherapy . Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks . One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day , both given for 5 days . Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy ; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy . The primary end point was overall survival . RESULTS We enrolled 1011 patients in the trial . There was no significant difference in overall survival between the groups that received chemotherapy preoperatively ( P=0.84 ) and those that received it postoperatively ( P=0.12 ) . The combined 5-year overall survival rate for all four groups was 65.2 % . The 5-year cumulative incidence rates for local recurrences were 8.7 % , 9.6 % , and 7.6 % in the groups that received chemotherapy preoperatively , postoperatively , or both , respectively , and 17.1 % in the group that did not receive chemotherapy ( P=0.002 ) . The rate of adherence to preoperative chemotherapy was 82.0 % , and to postoperative chemotherapy was 42.9 % . CONCLUSIONS In patients with rectal cancer who receive preoperative radiotherapy , adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival . Chemotherapy , regardless of whether it is administered before or after surgery , confers a significant benefit with respect to local control . ( Clinical Trials.gov number , NCT00002523 [ Clinical Trials.gov ] . ) The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil ( 5-FU ) was predictive for survival among patients with locally advanced rectal cancer . Preoperative chemoradiation ( CTX/XRT ) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU ( 300 mg/m2/day ) was given to 117 patients . The pretreatment stage distribution , as determined by endorectal ultrasound ( u ) , included uT2N0 in 2 % , uT3N0 in 47 % , uT3N1 in 49 % , and uT4N0 in 2 % of cases ; endorectal ultrasound was not performed in 13 % of cases ( 15 patients ) . Approximately 6 weeks after completion of CTX/XRT , surgery was performed . Adjuvant chemotherapy , consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days , was administered every 28 days for 4 to 6 cycles after surgical resection . Among the 74 patients treated with adjuvant chemotherapy , the preoperative stage of disease was 31 with T3N0 and 43 T3N1 . Median follow-up was 46 months ( range 2 to 89 months ) . The pathologic tumor stages were Tis-2N0 in 26 % , T2N1 in 5 % , T3N0 in 21 % , T3N1 in 15 % , T4N0 in 5 % , and T4N1 in 1 % ; a complete response ( CR ) to preoperative CTX/XRT was pathologically confirmed in 32 ( 27 % ) of patients . Tumor down-staging occurred in 72 ( 62 % ) cases . A sphincter-saving procedure ( SP ) was possible in 59 % of patients . The median DFS and overall survival rates for responders were 46 months and 47 months , respectively ; for non-responders these outcome measures were 38 months and 41 months , respectively . Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT ( p < 0.00001 ) , CR to CTX/XRT ( p < 0.009 ) and SP ( p < 0.012 ) . Likewise , these parameters also significantly influenced DFS rates ( CTX/XRT p < 0.00001 ; CR p < 0.006 ; and SP p < 0.008 ) . Control of pelvic disease was influenced by clinical size ( p < 0.002 ) and SP ( p < 0.016 ) on univariate analysis . On multivariate analysis only clinical size ( p < 0.002 ) continued to be a significant factor for local control . Factors on multivariate analysis that result ed in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT ( p < 0.017 ) and administration of adjuvant chemotherapy ( p < 0.034 ) . Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates . Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer . Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy PURPOSE To calculate the generic planning target margin ( GPTM ) for patients receiving radiation therapy ( RT ) for rectal cancer placed in a prone position with a customized cradle for small-bowel exclusion . METHODS AND MATERIAL S A total of 25 consecutive rectal cancer patients were treated for 25 or 28 fractions in a prone position using a cradle to maximize small bowel exclusion . Treatment planning computed tomography ( CT ) scans were used to create orthogonally digitally reconstructed radiographs ( DRRs ) for portal image registration , which were compared with daily portal images from an electronic portal-imaging device ( EPID ) . Translation values needed to align the DRRs and EPIDs were recorded for the superior to inferior ( SI ) , right to left ( RL ) , and anterior to posterior ( AP ) directions , and used to calculate the GPTM using the four-parameter model . Age , weight , and body mass index were tested compared with the setup variation using a Pearson correlation and a t test for significance . Gender versus setup variation was compared with a t test . RESULTS A total of 1,723 EPID images were review ed . The GPTM was 10 mm superior , 8 mm inferior , 7 mm RL and 10 mm AP . Age and gender were unrelated to setup variation . Weight was significantly associated with systematic AP variation ( p < 0.05 ) . BMI was significantly associated with systematic SI ( p < 0.05 ) and AP ( p < 0.01 ) variation and r and om RL variation ( p < 0.05 ) . CONCLUSIONS The GPTM for rectal cancer is asymmetric with a maximum of 10 mm in the superior , anterior and posterior dimensions . Body mass index may effect setup variation . Research using advanced treatment planning should include these margins in the planning target volume definition PURPOSE To investigate the impact of rectum motion on dose - volume histograms of the rectum including filling and of the wall ( DVH and DWH , respectively ) , during 3D-conformal radiotherapy ( 3DCRT ) for localized prostate cancer . MATERIAL S AND METHODS Ten patients received a planning CT scan ( CT(0 ) ) and 11 - 14 CT during 3DCRT for prostate cancer ( total CT scans=126 ) . CT images were 3D matched using bony anatomy . A single observer drew the external contours of rectum and rectum wall and the CTV ( prostate + seminal vesicles ) on CT(0 ) . Patients were asked to empty their rectum before every CT , as generally performed at the Institute for Cancer Research and Treatment ( IRCC ) before treatment delivery . Bladder was kept full by drinking 500 cm(3 ) of water 60 min before the scan , according to our protocol . A 4-field box 3DCRT technique was planned and dose statistics/dose - volume histograms of the rectum were calculated for each contour referred to CT(0),CT(1), ... ,CT(n ) for each patient . Average DVHs during treatment were calculated along with their st and ard deviation ( SD(r and ) ) and compared to the planned DVH . The analyses on the patient population included the assessment of systematic deviation ( average difference and SD , named SD(sys ) ) as well as the average SD(r and ) value expressing the r and om component of organ motion . Rectum shifts were also assessed by anterior and lateral BEV projections . RESULTS As to the rectum , 8/10 patients showed a " better " average DVH than DVH on CT(0 ) . Wilcoxon test showed a statistically significant reduction when correlating the difference Delta between the average DVH during therapy and planning DVH at CT(0 ) : for instance V(70)Delta = -3.6 % and p = 0.022 , V(50)Delta = -5.5 % and p = 0.022 , D(med)Delta = -3.2 Gy and p = 0.007 . Average values of DVH systematic difference ( average difference between planning scan and treatment ) , st and ard deviations ( SD(sys ) ) and average st and ard deviations of the r and om fluctuation ( SD(r and om ) ) were -4.0 % , 4.7 % and 6.6 % , respectively . Whilst the fluctuation results were slightly smaller for DWH . Volume analysis showed a slight systematic variation of the rectal volume between planning and treatment BEV . The average rectal volume during therapy was larger than at the planning CT in 8/10 patients . The systematic shifts of the rectal wall between the planning phase and the treatment were rather small , both below and above the flexure . The larger r and om fluctuation of the rectum shape was found to be in the cranial half ( 1 SD=4.4 mm ) . CONCLUSIONS The practice of carefully emptying the rectum during simulation and therapy for prostate cancer , which is a safe and simple procedure , reduces the impact of organ motion on dose - volume parameters of the rectum PURPOSE To quantify the day-to-day target volume shape variation in rectal-cancer patients treated with preoperative 5x5Gy radiotherapy . MATERIAL S AND METHODS For 27 patients a prone position plan-CT ( pCT ) and five daily pre-treatment cone-beam-CT ( CBCT ) scans were acquired . A sub-region of the CTV ( MesoRect , anus up to the cranial end of the mesorectal-fascia ) was delineated on all scans . The MesoRect deformation was quantified by the distance between pCT- and CBCT-delineations and was stored in surface-maps . Finally , the influence of bladder and rectum filling on MesoRect deformation was evaluated . Data were analyzed for male and female patients separately . RESULTS A large range of systematic and r and om deformations , 1 - 7 mm ( 1SD ) , on different areas of the MesoRect were found . The maximum deformations were located at the upper-anterior-side of the MesoRect . For females the errors were up to 3 mm larger than for males . Small correlations , r(2)0.4 , were found with changes in bladder volume . Larger correlations , r(2)0.7 , were found for rectal volume in a distinctive area in the upper-half of the MesoRect . CONCLUSIONS Substantial and heterogeneous deformations of the MesoRect were found . Therefore different PTV margins in positions along the cranio-caudal axis , in the anterior-posterior direction . Margins should also be larger for female patients compared to male patients |
592 | 22,339,194 | In conclusion , isepamicin might be active in vitro against Gram-negative bacteria with resistance to amikacin and other aminoglycosides | We sought to review the potential role of isepamicin against infections with contemporary Gram-negative bacteria . | Isepamicin is a new aminoglycoside antibiotic which possesses greater stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides . In this prospect i ve , r and omised , open trial , the safety and efficacy of intravenous administration of isepamicin was compared with that of intravenous amikacin in seriously ill adults with nosocomial pneumonia or septicaemia . Each study aminoglycoside was administered concurrently with ceftazidime or imipenem . Patients were r and omised to receive isepamicin 15 mg/kg once daily , isepamicin 7.5 mg/kg twice daily or amikacin 7.5 mg/kg twice daily . For patients with nosocomial pneumonia , the proportions of patients in the intent-to-treat population ( n = 130 ) who were clinical ly cured at the end of treatment were similar in each treatment group : 18/44 ( 41 % ) isepamicin once daily ; 19/45 ( 42 % ) isepamicin twice daily ; and 17/41 ( 42 % ) amikacin . Corresponding results for the efficacy population ( n = 58 ) were : 12/20 ( 60 % ) isepamicin once daily ; 14/21 ( 67 % ) isepamicin twice daily ; 9/17 ( 53 % ) amikacin . In patients with septicaemia , clinical cure was achieved in 8/10 ( 80 % ) patients treated with isepamicin once daily , compared with 8/13 ( 62 % ) patients who received isepamicin twice daily , and 7/12 ( 58 % ) patients treated with amikacin . For both diagnoses , there were no statistically significant differences between the treatment groups in clinical cure rate . The most commonly isolated target pathogen was Pseudomonas aeruginosa . For both nosocomial pneumonia and septicaemia , the proportion of patients in the intent-to-treat population whose pretreatment valid target pathogens were eliminated was similar in each treatment group . In total , 51 patients ( 30 % ) died during study , mostly due to disease progression or complications , or concurrent illness . All three treatment regimens were well tolerated . The proportion of patients experiencing at least one adverse event was 11 % , 25 % and 9 % for isepamicin once daily , isepamicin twice daily and amikacin , respectively . The incidence of ototoxicity and nephrotoxicity was relatively low in both treatment groups We evaluated the antimicrobial activity of fosfomycin against a r and omly selected sample of 30 Klebsiella pneumoniae , 30 Pseudomonas aeruginosa , and 30 Acinetobacter baumannii multidrug-resistant , clinical isolates from patients in a general tertiary care hospital in Athens , Greece . St and ard laboratory methods were used for susceptibility testing to commonly used antibiotics and the detection of extended-spectrum-β-lactamase ( ESBL ) and metallo-β-lactamase ( MBL ) production . The minimum inhibitory concentration ( MIC ) of fosfomycin for each isolate was determined by the agar dilution method . All K. pneumoniae isolates were both ESBL and MBL producers ; all P. aeruginosa isolates were ESBL producers . The K. pneumoniae strains had fosfomycin MICs distributed across a range of 8 - 64 μg/ml ; MIC50 was 16 μg/ml and MIC90 32 μg/ml . The fosfomycin MICs of the P. aeruginosa strains had a distribution across a range of 4 to over 512 μg/ml ; MIC50 was 32 μg/ml and MIC90 128 μg/ml . The fosfomycin MICs of the A. baumannii strains had a distribution across a range of 64 to over 512 μg/ml ; MIC50 was 256 μg/ml and MIC90 more than 512 μg/ml . Although st and ardized fosfomycin MIC interpretative breakpoints for the species studied are lacking , the findings of our study support the idea that fosfomycin may be further investigated as one among a decreasing list of therapeutic options for the treatment of infections due to multidrug-resistant strains of , primarily , K. pneumoniae and , secondly , P. aeruginosa In a prospect i ve multicentre open trial , hospitalised adult patients with acute lower respiratory tract infections , mainly pneumonia or bronchitis , were r and omised to receive either isepamicin 8 or 15 mg/kg once daily depending on the severity of the infection or amikacin 7.5 mg/kg twice daily . Patients with infections known to be caused by Pseudomonas aeruginosa were to be given concomitant treatment with ceftazidime . In the intent-to-treat population , i.e. patients who received at least one dose r and omised treatment , a clinical cure or improvement at the end of treatment was seen in 112/125 ( 90 % ) isepamicin patients and 55/60 ( 92 % ) amikacin patients . The corresponding rates for patients with a primary diagnosis of pneumonia were 45/52 ( 87 % ) and 25/28 ( 89 % ) . Cure/improvement rates for patients with P. aeruginosa as the causative pathogen ( 34 of whom also received ceftazidime ) were 28/30 ( 93 % ) and 16/18 ( 89 % ) , respectively . In the efficacy population ( patients who had a valid pretreatment culture and who met other evaluability criteria ) , total elimination ( documented or presumed if infection had resolved ) of target pathogens occurred in 54/63 ( 86 % ) of isepamicin patients and 25/30 ( 83 % ) of amikacin patients . P. aeruginosa , Escherichia coli , Klebsiella pneumoniae and Staphylococcus aureus were commonly isolated pathogens . Treatment-related adverse were mainly mild or moderate in severity and occurred in 10 % of isepamicin patients and 13 % of amikacin patients . Four patients ( 3 isepamicin and 1 amikacin ) discontinued treatment because of severe adverse events and a further isepamicin patient withdrew because of a mild adverse event . Nephrotoxicity and ototoxicity occurred infrequently Intensive care unit (ICU)-acquired infections as a result of multidrug-resistant Gram-negative pathogens remain a serious problem in critically ill patients . Adult ICU patients who received intravenous fosfomycin were prospect ively examined to assess its safety and effectiveness as an adjunct to the antimicrobial therapy of life-threatening infections caused by carbapenem-resistant Klebsiella pneumoniae . Fosfomycin was administered intravenously in 11 patients for treatment of hospital-acquired infections caused by carbapenem-resistant K. pneumoniae . Fosfomycin ( 2 - 4 g every 6 h ) was administered in combination with other antibiotics . The mean + /- SD duration of treatment was 14 + /- 5.6 days . All patients had good bacteriological and clinical outcome of infection . All-cause hospital mortality was two out of 11 ( 18.2 % ) patients . No patient experienced adverse events related to the administration of fosfomycin . Intravenous fosfomycin may be a beneficial and safe adjunctive treatment in the management of life-threatening ICU-acquired infections caused by carbapenem-resistant K. pneumoniae ABSTRACT Directed evolution by r and om PCR mutagenesis of the gene for the aminoglycoside 2″-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes , result ing in elevated levels of resistance to amikacin and isepamicin but not to other aminoglycoside antibiotics . Increases in the activities of the mutant phosphotransferases for isepamicin are the result of decreases in Km values , while improved catalytic efficiency for amikacin is the result of both a decrease in Km values and an increase in turnover of the antibiotic . Enzymes with R92H , D268N , and D268N single amino acid substitutions did not result in elevated MICs for aminoglycosides Two hundred and three patients with skin and skin structure infections were treated with isepamicin once daily or amikacin twice daily in an open , r and omised , comparative multicentre trial . Patients were r and omised to treatment with isepamicin or amikacin in a 2:1 ratio . Severe infections ( 63 patients ) were treated with isepamicin 15 mg/kg once daily ( n = 15 ) or amikacin 7.5 mg/kg twice daily ( n - 18 ) , less severe infections ( 140 patients ) with isepamicin 8 mg/kg once daily ( n = 93 ) or amikacin 7.5 mg/kg twice daily ( n = 47 ) . The overall clinical response rate at the end of treatment was excellent in all treatment groups ( 94 - 96 % cured or improved ) with no significant differences between isepamicin and amikacin in patients with either server or less severe infections . The most commonly isolated target pathogens were Pseudomonas aeruginosa , Escherichia coli , Proteus mirabilis and Staphylococcus aureus . Overall , in patients who had a valid target pathogen isolated prior to treatment and who met other evaluability criteria , bacteriological eradication was achieved in over 90 % of patients ; amikacin patients with severe infections had a somewhat lower eradication rate ( 82 % ) . Over all infections , 4/110 ( 4 % ) patients in the isepamicin group and 5/54 ( 9 % ) patients in the amikacin had organisms which persisted . Adverse events were reported in 12 % of patients in the isepamicin group and 6 % in the amikacin group . The most frequently reported adverse event in the isepamicin group as headache . Two patients ( one in each treatment group ) , both of whom experienced skin rashes , were withdrawn . Potentially clinical ly significant changes in serum creatinine occurred in two patients , who received isepamicin and one who received amikacin ( who was withdrawn from the study ) . Ototoxicity was rare , occurring in one patient treated with isepamicin In this study we compared the efficacy and safety of isepamicin versus amikacin at a dose of 7.5 mg/kg i.v . q12h for 10 - 14 days in children with pyelonephritis . Sixteen children were enrolled in the study ; ten received isepamicin and six amikacin . Urine cultures grew Escherichia coli in all patients . All patients were treated successfully with either isepamicin or amikacin . Clinical and bacteriological response rates were 100 % for both groups . No adverse events occurred . Peak serum levels ranged from 9.05 to 30.70 mg/l ( median : 16.165 ) and from 12.20 to 25.90 mg/l ( median : 19.05 ) for isepamicin and amikacin , respectively . Trough serum levels ranged from 0.11 to 3.20 mg/l ( median : 0.75 ) and from 0.1 to 2.1 mg/l ( median : 0.655 ) , respectively . Isepamicin was shown to be as effective and safe as amikacin in the treatment of children with pyelonephritis and might prove an advantageous alternative in areas with high incidence of resistance to other aminoglycosides The efficacy and safety of isepamicin 7.5 mg/kg of body weight twice daily or amikacin the same dosage regimen for the treatment of various infections in neutropenic and non-neutropenic paediatric patients were compared in a prospect i ve r and omised trial . In total , 306 patients were enrolled and received at least one dose of r and omised treatment ( 204 isepamicin , 102 amikacin : intent-to-treat population ) ; 181 patients satisfied all criteria for evaluability ( 120 isepamicin , 61 amikacin : efficacy population ) . Clinical cure or improvement rates in the isepamicin and amikacin groups were : intent-to-treat population , 188/204 ( 92 % ) and 94/102 ( 92 % ) , respectively ; efficacy population , 117/120 ( 98 % ) and 58/61 ( 95 % ) , respectively . The bacteriological elimination rate ( efficacy population ) in the isepamicin and amikacin treatment groups was 75/76 ( 99 % ) vs 35/38 ( 92 % ) . Nephrotoxicity , defined as an increase in serum creatinine of 0.5 mg/dL or > or = 44.2 mumol/L from baseline , occurred in 4/187 ( 2 % ) and 1/191 ( 1 % ) children treated with isepamicin and amikacin , respectively . Definite ototoxicity at the > or = 20 dB threshold occurred in 3 ( 1 isepamicin and 2 amikacin ) out of 56 children evaluated with at least two audiograms . Thus isepamicin was as effective and as well tolerated as amikacin in the treatment of various infections in paediatric patients The efficacy and safety of isepamicin at 7.5 mg/kg i.v . q 12 h was prospect ively compared with that of amikacin at the same dose for the treatment of febrile neutropenic children with malignancies . Thirty-nine patients were enrolled in the study ; 25 received isepamicin and 14 amikacin . Clinical and bacteriological response rates were 100 % for both groups . No adverse events occurred . Median peak serum levels were 19.7 mg/l for isepamicin and 19.20 mg/l for amikacin . Median trough serum levels were 0.72 mg/l for isepamicin and 0.68 mg/l for amikacin . It was concluded that isepamicin was as effective and safe as amikacin for the treatment of febrile neutropenic children with malignancies , and might be used in areas where resistance to other aminoglycosides is a problem |
593 | 12,917,911 | REVIEW ER 'S CONCLUSIONS Brief counselling interventions , successful in the adult health setting when coming from physicians , can not be extrapolated to adults in the setting of child health .
There is limited support for more intensive counselling interventions .
There is no clear evidence for differences between the respiratory , non-respiratory ill child , well child and peripartum setting s as context s for reduction of children 's ETS exposure | BACKGROUND Exposure to other people 's cigarette smoke ( environmental tobacco smoke , or ETS ) is an important child health issue .
OBJECTIVES To determine the effectiveness of interventions aim ing to reduce exposure of children to ETS . | BACKGROUND A multicomponent motivational smoking cessation intervention was evaluated in 33 prenatal , family planning , and pediatric services in 12 public health clinics . Clinic-based intervention components were implemented by clinic personnel as part of routine medical visits . METHODS The evaluation design included pre- and postintervention measurements of multiple study outcomes in a baseline ( all clinics prior to the start of the intervention ) and an experimental period ( matchedpair r and om assignment of clinics to intervention or control conditions ) . Subjects were 683 ( baseline ) and 1,064 ( experimental ) smokers with measurements of smoking outcomes at both times . Mixed-effects regressions analyzed individual outcomes clustered within clinics and services . RESULTS Control and intervention clinics had similar outcomes in the baseline period . In the experiment , outcomes improved in the intervention but not in the control clinics . Compared to controls , smokers exposed to the intervention were more likely to have quit ( 14.5 versus 7.7 % ) or take actions toward quitting and had higher mean action , stage of readiness , and motivation to quit scores . These positive effects persisted when clustering within clinics and services was controlled . CONCLUSIONS This intervention , implemented by clinic personnel as part of routine medical visits , was effective under these natural conditions across different types of clinic service BACKGROUND Pediatric well-care visits provide a clinical opportunity to counsel new mothers about their smoking and the deleterious effects of environmental tobacco smoke ( ETS ) on infant health . METHODS Forty-nine Oregon pediatric offices enrolled 2,901 women who were currently smoking or had quit for pregnancy , using a brief survey at the newborn 's first office visit . R and omly assigned offices provided advice and material s to mothers at each well-care visit during the first 6 months postpartum to promote quitting or relapse prevention . RESULTS The intervention reduced smoking ( 5.9 % vs 2.7 % ) and relapse ( 55 % vs 45 % ) at 6-month follow-up , but logistic regression analysis at 12 months revealed no significant treatment effect . The intervention had a positive effect on secondary outcome variables , such as readiness to quit and attitude toward and knowledge of ETS . Multiple logistic regression analysis indicated that husb and /partner smoking was the strongest predictor of maternal quitting or relapse . CONCLUSIONS A pediatric office-based intervention can significantly affect smoking and relapse prevention for mothers of newborns , but the effect decreases with time . Consistent prompting of the provider to give brief advice and material s at well-care visits could provide a low-cost intervention to reduce infant ETS exposure BACKGROUND Since most smoker parents of children with asthma are unable to quit , an alternative measure that would reduce their children 's exposure to environmental tobacco smoke ( ETS ) is to ban smoking in the home . METHODS Compared with 136 usual-care controls , 128 intervention-group parents recruited from South Australian pediatric hospital outpatient waiting rooms were given written and verbal feedback about their 1- to 11-year-old child 's urinary cotinine-to-creatinine level , information booklets , and two telephone calls encouraging a ban on smoking at home . RESULTS At 6 months , 49.2 % of the intervention group reported having banned smoking in the home compared with 41.9 % of controls , but the differential rate of change from baseline was not significant ( P = 0.40 ) . At follow-up , there were no significant differences between groups in the percentage reporting bans on smoking in the car , the mean reduction from baseline in total daily consumption or consumption in front of the child , children 's urinary cotinine level , or parental smoking cessation . CONCLUSIONS The intervention did not change parents ' propensity to create or maintain bans on smoking in their homes or otherwise change smoking habits to reduce their children 's exposure to ETS . More intensive interventions may be required to achieve change among low-income smoker parents of children with asthma OBJECTIVE To examine the effects of environmental tobacco smoke ( ETS ) on health services use in Chinese infants with nonsmoking mothers . DESIGN Prospect i ve , population -based birth cohort . SETTING General population of Hong Kong in 1997 - 1998 . PARTICIPANTS A total of 8327 parent-infant pairs who were followed up for 18 months . MAIN OUTCOME MEASURES Doctor consultations and hospitalizations . Results . After adjusting for the age , education level , and employment status of mothers-as well as infants ' birth weight , method of delivery , breastfeeding status , and birth order-ETS exposure through the mother in utero was positively associated with higher consultation ( adjusted odds ratio [ OR ] : 1.26 ; 95 % confidence interval [ CI ] : 1.14 , 1.39 ) and hospitalization ( OR : 1.18 ; 95 % CI : 1.05 , 1.31 ) use in infants with nonsmoking mothers attributable to any illness . In addition , postnatal exposure to ETS at home was linked to higher rates of hospitalizations for any illness compared with nonexposed infants ( OR : 1.12 ; 95 % CI : 1.00 , 1.25 ) , although the relationship did not hold for outpatient consultation visits . The OR for higher hospital use in infants exposed to 2 or more smokers at home was 1.30 ( 95 % CI : 1.08 , 1.58 ) . CONCLUSIONS The use of tobacco products by household members , even among nonsmoking mothers , has an enormous adverse impact on the health of children , as well as increases health services use and cost . The present data support the revision of public policy to reflect an evidence -based approach to the promotion of smoking cessation in all household members during and after pregnancy . environmental tobacco smoke , health services , infants Abstract Objective : To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke . Design : R and omised controlled trial . Setting : Tayside and Fife , Scotl and . Participants : 501 families with an asthmatic child aged 2 - 12 years living with a parent who smoked . Intervention : Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child 's health . Main outcome measures : Salivary cotinine concentrations in children , and changes in reported smoking habits of the parents 1 year after the intervention . Results : At the second visit , about 1 year after the baseline visit , a small decrease in salivary cotinine concentrations was found in both groups of children : the mean decrease in the intervention group ( 0.70 ng/ml ) was slightly smaller than that of the control group ( 0.88 ng/ml ) , but the net difference of 0.19 ng/ml had a wide 95 % confidence interval ( −0.86 to 0.48 ) . Overall , 98 % of parents in both groups still smoked at follow up . However , there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking . Conclusions : A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children 's exposure to environmental tobacco smoke . The intervention may have made some parents less inclined to stop smoking . If a clinician believes that a child 's health is being affected by parental smoking , the parent 's smoking needs to be addressed as a separate issue from the child 's health . Key messages Many asthmatic children are exposed to high levels of environmental tobacco smoke A brief intervention informing parents of asthmatic children on the harmful effects of passive smoking did not lead to a reduction in exposure of their children to tobacco smoke Low rates of smoking cessation were found in both the intervention group and the control group Some parents may have been less inclined to stop smoking after the intervention Brief interventions requesting smokers to stop for another person 's health seem We conducted a r and omized controlled trial to determine whether a home-based intervention program could reduce infant passive smoking and lower respiratory illness . The intervention consisted of four nurse home visits during the first 6 months of life , design ed to assist families to reduce the infant 's exposure to tobacco smoke . Among the 121 infants of smoking mothers who completed the study , there was a significant difference in trend over the year between the intervention and the control groups in the amount of exposure to tobacco smoke ; infants in the intervention group were exposed to 5.9 fewer cigarettes per day at 12 months . There was no group difference in infant urine cotinine excretion . The prevalence of persistent lower respiratory symptoms was lower among intervention-group infants of smoking mothers whose head of household had no education beyond high school : intervention group , 14.6 % ; and controls , 34.0 % 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 An information programme on measures to prevent passive smoking by children , design ed for use during well‐child visits , was tested . A total of 443 consecutive families with one or two smoking parents , attending mother and child health centres in Oslo , Norway , were r and omly allocated to an intervention group ( n= 221 ) and a control group ( n= 222 ) . Eighty families ( 18 % ) dropped out during the study period . For the intervention group , the communication between the health visitor and the family was prolonged at one well‐child visit with a brief session on smoking , and the parents were given three brochures . The families in the control group received no information on smoking . Changes in practical measures to prevent passive smoking by the children ( e.g. no smoking indoors ) as well as changes in daily smoking and smoking quantity were assessed by parental reports . We found no significant differences between the groups with respect to change in smoking behaviour BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multistate field trial examining the effects of school environment , classroom curricula , and family intervention components in promoting the cardiovascular health of elementary school students . The purpose of this paper is to describe the CATCH tobacco use intervention and measurement , including the adoption of tobacco-free school policies . METHODS In this study , changes in school tobacco use policies and smoking experimentation among students were assessed . Smoking experimentation was measured in all CATCH schools when the students were in their fifth- grade year . A total of 6,527 subjects in 96 schools in California , Louisiana , Minnesota , and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior question naire in Spring 1994 . School tobacco use policy , an important complement to classroom- and home-based prevention efforts , was promoted as part of the CATCH intervention . The degree to which such policy was implemented was measured using surveys of school officials . RESULTS At the end of fifth grade , only 4.8 % of the subjects indicated that they had experimented with tobacco . School intervention condition was not a factor in the prediction of experimentation . Those whose best friend or sibling smoked , or who had ready access to cigarettes in the home , were more likely to have experimented with smoking . In the 3 years of the study , the percentages of tobacco-free schools went up from 49.7 to 76.8 % . Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention , the implementation of the tobacco-free schools ' policies did vary substantially from state to state . Minnesota and Texas , with stronger state laws supporting local policy , had nearly completely smoke-free schools . In spite of a statewide tobacco control initiative , California was slower to implement school policies . Louisiana , which allows local decision making regarding smoking policy , had the most difficulty establishing a policy for all districts . CONCLUSION Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels . Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district STUDY OBJECTIVES To determine the effectiveness of a cotinine-feedback , behaviorally based education intervention in reducing environmental tobacco smoke ( ETS ) exposure and health-care utilization of children with asthma . DESIGN R and omized controlled trial of educational intervention vs usual care . SETTING The pediatric pulmonary service of a regional pediatric hospital . PARTICIPANTS ETS-exposed , Medicaid/Medi-Cal-eligible , predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital 's emergency , inpatient , and outpatient services departments ( n = 87 ) . INTERVENTION Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child 's urinary cotinine level . MEASUREMENTS The primary measurements were the urinary cotinine/creatinine ratio ( CCR ) and the number of acute asthma medical visits . The secondary measurements were number of hospitalizations , smoking restrictions in home , amount smoked , reported exposures of children , and asthma control . RESULTS The intervention was associated with a significantly lower odds ratio ( OR ) for more than one acute asthma medical visit in the follow-up year , after adjusting for baseline visits ( total visits , 87 ; OR , 0.32 ; p = 0.03 ) , and a comparably sized but nonsignificant OR for one or more hospitalization ( OR , 0.34 ; p = 0.14 ) . The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group ( n = 51 ) ( mean difference in CCR adjusted for baseline , -0.38 ; p = 0.26 ; n = 51 ) ( 60 ; OR [ for proportion of subjects prohibiting smoking ] , 0.24 ; p = 0.11 ; n = 60 ) . CONCLUSIONS This intervention significantly reduced asthma health-care utilization in ETS-exposed , low-income , minority children . Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant , possibly the result of reduced precision due to the loss of patients to active follow-up . Improving ETS reduction interventions and underst and ing their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently Because preschoolers and first grade rs show signs of readiness to try smoking and because they are already learning about smoking through their environment , smoking prevention at the preschool level is appropriate . The large numbers of children seen in primary care practice s and day care facilities are indicative of the numbers that could be exposed to smoking prevention instruction through these setting s. This study assessed the future expectations of children to protect themselves from sidestream smoke after participating in a preschool smoking prevention program offered in four primary care setting s. Through this program , children and their parents read stories and complete activities concerning the human body and the health risks of smoking . Using a r and omized posttest-only case control design , the authors found that children who were exposed to the curriculum were more than twice as likely as others to report the intention to act to protect themselves from adult sidestream smoke Abstract Objective : To test the efficacy of behavioural counselling for smoking mothers in reducing young children 's exposure to environmental tobacco smoke . Design : R and omised double blind controlled trial . Setting : Low income homes in San Diego county , California . Participants : 108 ethnically diverse mothers who exposed their children ( aged < 4 years ) to tobacco smoke in the home . Intervention : Mothers were given seven counselling sessions over three months . Main outcome measures : Children 's reported exposure to environmental tobacco smoke from mothers in the home and from all sources ; children 's cotinine concentrations in urine . Results : Mothers ' reports of children 's exposure to their smoke in the home declined in the counselled group from 27.30 cigarettes/week at baseline , to 4.47 at three months , to 3.66 at 12 months and in the controls from 24.56 , to 12.08 , to 8.38 . The differences between the groups by time were significant ( P=0.002 ) . Reported exposure to smoke from all sources showed similar declines , with significant differences between groups by time ( P=0.008 ) . At 12 months , the reported exposure in the counselled group was 41.2 % that of controls for mothers ' smoke ( 95 % confidence interval 34.2 % to 48.3 % ) and was 45.7 % ( 38.4 % to 53.0 % ) that of controls for all sources of smoke . Children 's mean urine cotinine concentrations decreased slightly in the counselled group from 10.93 ng/ml at baseline to 10.47 ng/ml at 12 months but increased in the controls from 9.43 ng/ml to 17.47 ng/ml ( differences between groups by time P=0.008 ) . At 12 months the cotinine concentration in the counselled group was 55.6 % ( 48.2 % to 63.0 % ) that of controls . Conclusions : Counselling was effective in reducing children 's exposure to environmental tobacco smoke . Similar counselling in medical and social services might protect millions of children from environmental tobacco smoke in their homes STUDY OBJECTIVE This r and omized clinical trial tested a behavioral medicine program design ed to reduce asthmatic children 's exposure to environmental tobacco smoke ( ETS ) in the home . DESIGN Families were r and omly assigned to an experimental preventive medicine counseling group , a monitoring control group , or a usual treatment control group . Families were measured six times over 1 year . PARTICIPANTS Ninety-one families were recruited from four allergy clinics . INTERVENTION The experimental group received a 6-month series of counseling sessions design ed to decrease ETS exposure . This group also monitored smoking , exposure , and children 's asthma symptoms . The monitoring group did not receive counseling and the usual treatment control group received outcome measures only . MEASUREMENTS AND RESULTS Parents reported the daily number of cigarettes children were exposed to during the week preceding interviews . A nicotine air monitor and construct validity analysis confirmed the validity of exposure reports . Exposure to the parent 's cigarettes in the home decreased for all groups . The experimental group attained a 79 percent decrease in children 's ETS exposure , compared with 42 percent for the monitoring control and 34 percent for the usual treatment control group . Repeated- measures analysis of variance result ed in a significant ( F([10,350 ] = 1.92 , p < 0.05 ) group by time effect . At the final 12-month visit , the experimental/counseling group sustained a 51 % decrease in children 's exposure to cigarettes in the home from all smokers , while the monitoring control group showed an 18 % decrease and the usual treatment control group a 15 % decrease from pre-intervention [ corrected ] . CONCLUSION A behavioral medicine program was successful in reducing exposure to ETS in the home for these asthmatic children OBJECTIVE Passive smoke exposure among children is widespread in the United States ; estimates suggest that almost 40 % of children who are younger than 5 years live with a smoker . Few r and omized studies of passive smoke exposure reduction among children have been conducted , and the impact of interventions that have been evaluated has been limited . The objective of this study was to determine whether a motivational intervention for smoking parents of young children will lead to reduced household passive smoke exposure . METHODS Project KISS ( Keeping Infants Safe From Smoke ) , a theory-driven exposure reduction intervention targeting low-income families with young children , was a r and omized controlled study in which participants -smoking parents/caregivers ( N = 291 ) who had children who were younger than 3 years and who were recruited through primary care setting s-were r and omly assigned to either the motivational intervention ( MI ) or a self-help ( SH ) comparison condition was used . Follow-up assessment s were conducted at 3 and 6 months . The MI condition consisted of a 30- to 45-minute motivational interviewing session at the participant 's home with a trained health educator and 4 follow-up telephone counseling calls . Feedback from baseline household air nicotine assessment s and assessment of the participant 's carbon monoxide level was provided as part of the intervention . Participants in the SH group received a copy of the smoking cessation manual , the passive smoke reduction tip sheet , and the re source guide in the mail . Household nicotine levels were measured by a passive diffusion monitor . RESULTS The 6-month nicotine levels were significantly lower in MI households . Repeated measures analysis of variance across baseline , 3-month , and 6-month time points showed a significant time-by-treatment interaction , whereby nicotine levels for the MI group decreased significantly and nicotine levels for the SH group increased but were not significantly different from baseline . CONCLUSIONS This study targeted a large sample of racially and ethnically diverse low-income families , in whom both exposure and disease burden is likely to be significant . This is the first study to our knowledge that has been effective in reducing objective measures of passive smoke exposure in households with healthy children . These findings have important implication s for pediatric health care providers , who play an important role in working with parents to protect children 's health . Providers can help parents work toward reducing household passive smoke exposure using motivational strategies and providing a menu of approaches regardless of whether the parents are ready to quit Exposure to environmental tobacco smoke is associated with increased respiratory morbidity in young children , but few studies have assessed such exposure objective ly by urinary cotinine measurements . 501 children aged 1 - 5 years , a r and om 5 % sample of children attending an outpatient clinic , were classified as exposed or non-exposed to environmental tobacco smoke with a cut-off of 10 ng cotinine per mg creatinine in urine . Exposed children were 3.5 times ( 95 % CI 1.56 - 7.90 , p < 0.0024 ) more likely to have increased respiratory morbidity ( three or more episodes during the previous 12 months ) than non-exposed children after adjustment for potential confounding factors Aims and Background We conducted a population -based trial to evaluate the efficacy of an intervention aim ed at preventing exposure of young children to parental tobacco smoke . Methods Of the 1142 eligible couples ( parents of newborn babies ) , 1015 were recruited ; the intervention was offered to 402 and not to 613 families . Results A strong association was found between social class and smoking behavior , in particular smoking during meals at home . The intervention itself had limited effectiveness In decreasing the number of smokers . The effect was stronger in mothers and in higher social groups . Among the « white-collar » families belonging to the intervention group , the proportion of mothers who stopped smoking was 3 times higher than in the control group ( not statistically significant ) . Conclusions Educational interventions against smoking should be planned taking into account the difference in efficacy according to social class Abstract Admissions to hospital during the first year of life were recorded in a prospect i ve study of 10,672 infants whose mothers ' smoking habits were known . Infants with major congenital malformations , and those dying before their first birthday , were excluded . The infants of mothers who smoked had significantly more admissions for bronchitis or pneumonia , especially in the winter , and more injuries . They were also admitted more frequently , though not significantly so , for upper-respiratory-tract infections , gastroenteritis , childhood infectious diseases , and other diagnoses . The excess of bronchitis and pneumonia in the group exposed to smoke increased with increasing number of cigarettes smoked by the mother . It occurred within subgroups of birth-weight , social class , and birth order . It was seen mainly in infants aged 6 - 9 months , while at older and younger ages there was no significant effect of maternal smoking . The findings support the hypothesis that atmospheric pollution with tobacco smoke endangers the health of non-smokers |
594 | 22,608,362 | It is anticipated that widespread adoption of these guidelines will further improve the accuracy of hormone receptor testing in Canada | Hormone receptor testing ( oestrogen and progesterone ) in breast cancer at the time of primary diagnosis is used to guide treatment decisions .
Accurate and st and ardised testing methods are critical to ensure the proper classification of the patient 's hormone receptor status . | 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 AIM --To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content ( oestrogen receptor index ) and proliferative activity ( MIB-1 index ) in breast cancer . METHODS --Two monoclonal antibodies , MIB-1 and oestrogen receptor , were applied to formalin fixed , paraffin wax embedded tissue from 25 prospect ively collected oestrogen receptor positive breast carcinomas , using a microwave antigen retrieval method . Tumour tissue was allocated systematic ally to different periods of fixation to ensure minimal intraspecimen variation . The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sample d systematic ally from the entire specimen and from the whole tumour area of one " representative " cross-section . RESULTS --No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation . The estimated MIB-1 and oestrogen receptor indices in tissue sample d systematic ally from the entire tumour were closely correlated with estimates obtained in a " representative " section . The intra- and interobserver correlation of the MIB-1 index was good , although a slight systematic al error at the second assessment of the intraobserver study was noted . CONCLUSION --Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin , varying from less than four hours to more than 48 hours . The MIB-1 and the oestrogen receptor indices obtained in a " representative " section do not deviate significantly from average indices determined in tissue sample s from the entire tumour . Finally , the estimation of MIB-1 index is reproducible , justifying its routine use OBJECTIVE To evaluate prospect ively the degree of correlation between immunocytochemical ( ICC ) and immunohistochemical ( IHC ) determination of estrogen ( ER ) and progesterone receptors ( PR ) in breast cancer . STUDY DESIGN Fine needle aspiration cytology ( FNAC ) of 101 primary breast cancers were immunostained for ER and PR . They were compared with similar determinations in formalin-fixed paraffin sections of biopsies from the same patients . In cases of discrepancy , the histologic result was considered the gold st and ard . RESULTS For ER a cytohistologic correlation of 94 % , with a sensitivity of 96.1 % and specificity of 86.9 % , was found . For PR the cytohistologic correlation was 71.2 % , with a sensitivity of 65.7 % and specificity of 83.8 % . CONCLUSION ICC determination of hormone receptors in routinely fixed smears obtained by FNAC is a simple method that correlates adequately with the results of IHC determinations , especially for ER Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment . We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy . Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6 ; treatment order was r and omly assigned . Pretreatment core biopsy sample s were interrogated for genes that might correlate with pathologic complete response ( pCR ) . In addition to the individual genes , the correlation of the Oncotype DX Recurrence Score with pCR was examined . Results Of 70 patients enrolled in the parent trial , core biopsies sample s with sufficient RNA for gene analyses were available from 45 patients ; 9 ( 20 % ) had inflammatory breast cancer ( IBC ) . Six ( 14 % ) patients achieved a pCR . Twenty-two of the 274 c and i date genes assessed correlated with pCR ( p < 0.05 ) . Genes correlating with pCR could be grouped into three large clusters : angiogenesis-related genes , proliferation related genes , and invasion-related genes . Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR . In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer ; twenty-four ( 9 % ) of the genes were differentially expressed ( p < 0.05 ) , 5 were upregulated and 19 were downregulated in IBC . Conclusion Gene expression analysis on core biopsy sample s is feasible and identifies c and i date genes that correlate with pCR to primary chemotherapy . Gene expression in IBC differs significantly from noninflammatory breast cancer The 21‐gene recurrence score ( RS ) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)‐positive , lymph node (LN)‐negative breast cancer who are treated with tamoxifen . To the authors ' knowledge , the association between the RS and clinicopathologic characteristics has been studied in r and omized and case‐control trials , but not in the general population PURPOSE To develop a guideline to improve the accuracy of immunohistochemical ( IHC ) estrogen receptor ( ER ) and progesterone receptor ( PgR ) testing in breast cancer and the utility of these receptors as predictive markers . METHODS The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance . RESULTS Up to 20 % of current IHC determinations of ER and PgR testing worldwide may be inaccurate ( false negative or false positive ) . Most of the issues with testing have occurred because of variation in preanalytic variables , thresholds for positivity , and interpretation criteria . RECOMMENDATIONS The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences . A testing algorithm that relies on accurate , reproducible assay performance is proposed . Elements to reliably reduce assay variation are specified . It is recommended that ER and PgR assays be considered positive if there are at least 1 % positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal ( normal epithelial elements ) and external controls . The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of r and omized clinical trials Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays . However , most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor , but unfortunately no vali date d immunohistochemical assay exists for progesterone receptor . The purpose of this study was to develop and vali date an immunohistochemical assay for progesterone receptor in breast cancer . The assay was based on monoclonal antibody 1294 ( DakoCytomation ) and slides were scored microscopically using the ‘ Allred score ’ on a scale of 0–8 . The assay was compared to lig and -binding assay in 1235 breast cancers , and a subset ( n=362 ) that received only hormonal therapy was used to define a cutoff for progesterone receptor-positive . Clinical utility was vali date d in an independent set of sample s ( n=423 ) from a clinical trial r and omizing premenopausal breast cancer patients to tamoxifen+oophorectomy vs observation following surgery . A cutoff of > 2 ( corresponding to > 1 % positive cells ) dichotomized patients with significantly better or worse clinical outcome ( P=0.0014 ) . Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by lig and -binding assay in predicting clinical outcome . In the clinical trial , a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated ( hazard ratios/P=0.656/0.060 and 0.479/0.005 , respectively ) and hormonally treated patients ( hazard ratios/P=0.529/0.017 and 0.451/0.007 , respectively ) . Positive progesterone receptor remained significant for improved disease-free and overall survival ( hazard ratios/P=0.666/0.038 and 0.549/0.007 , respectively ) in multivariate analyses including the st and ard variables of tumor size , nodal status , treatment , histological grade , and HER-2/neu status . Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis . This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer . Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by lig and -binding assay Purpose : Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor – positive breast cancer , and it still remains important due to its well-documented beneficial effect . Hormone receptor status is often reported as “ positive ” or “ negative ” using 10 % positive nuclei as a cutoff . In this study , we aim ed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value . Experimental Design : The immunohistochemical expression of estrogen receptor ( ER ) and progesterone receptor ( PR ) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a r and omized trial of adjuvant tamoxifen compared with an untreated control group . Results : Our findings show a gradually increasing tamoxifen effect in tumors with > 10 % ER-positive nuclei . However , when analyzing tamoxifen response according to various PR fractions , we found that it was primarily patients with tumors showing > 75 % PR-positive nuclei that responded to tamoxifen treatment , with an improved recurrence-free [ relative risk , 0.42 ( 0.25 - 0.70 ) ; P = 0.001 ] as well as overall [ relative risk , 0.49 ( 0.28 - 0.84 ) ; P = 0.010 ] survival . Conclusions : Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing > 75 % PR-positive nuclei . No effect could be shown in tumors with fewer PR-positive nuclei . The PR was a stronger predictor of treatment response than the ER . Based on these findings , we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice , possibly with greater emphasis on the PR than the ER Aim : To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment . Methods : The treatment group consisted of 31 patients with operable breast carcinomas , median age 57 years ( range 41–67 ) , treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone , methotrexate ( ± mitomycin C ) , and tamoxifen before surgery . Fine needle aspiration ( FNA ) was used to obtain sample s from patients prior to and at 10 or 21 days post‐treatment . The following molecular markers were assessed : estrogen receptor ( ER ) , progesterone receptor ( PgR ) , p53 , Bcl‐2 , and Ki67 measured by immunocytochemistry , and ploidy and S‐phase fraction ( SPF ) by flow cytometry . To evaluate the reproducibility of the technique , repeat FNA was performed in a separate non‐treatment control group of 20 patients and the same molecular markers assessed , two weeks after the first sample with no intervening treatment . Results : The non‐treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA . In the treatment group there was a non‐significant reduction in SPF and a significant reduction ( p = 0.005 ) in Ki67 . Patients who responded to neoadjuvant therapy were more likely to have a reduction in these two markers than those who failed to respond . Similarly , a reduction in ER scores was observed between the first and second sample s ( p = 0.04 ) . For PgR , the change between the first and second sample s was not significant although there was a significant difference between responders and non‐responders ( p = 0.03 ) . All nine patients with an increase in PgR were responders . No significant changes in p53 or Bcl‐2 were observed during treatment . Conclusion : Molecular markers can be adequately measured from FNA sample s prior to and during neoadjuvant therapy . Changes in cellular proliferation and hormone receptors have been shown that may be related to tumour response . These relationships should be assessed in a larger cohort of patients Previously , we had identified gene expression patterns that predicted response to neoadjuvant docetaxel . Other studies have vali date d that a high Recurrence Score ( RS ) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy . We investigated whether tumor expression of these 21 genes and other c and i date genes can predict response to docetaxel . Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel ( 4 cycles , 100 mg/m2 q3 weeks ) . Three 10-μm FFPE sections were su bmi tted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature . Of the 97 patients , 81 ( 84 % ) had sufficient invasive cancer , 80 ( 82 % ) had sufficient RNA for QRTPCR assay , and 72 ( 74 % ) had clinical response data . Mean age was 48.5 years , and the median tumor size was 6 cm . Clinical complete responses ( CR ) were observed in 12 ( 17 % ) , partial responses in 41 ( 57 % ) , stable disease in 17 ( 24 % ) , and progressive disease in 2 patients ( 3 % ) . A significant relationship ( P < 0.05 ) between gene expression and CR was observed for 14 genes , including CYBA . CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay . Of note , CR was more likely with a high RS ( P = 0.008 ) . We have established molecular profiles of sensitivity to docetaxel . RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material CONTEXT Estrogen receptors ( ER ) and progesterone receptors ( PR ) play a significant role in the prognosis of breast cancer . For preoperative chemotherapy in locally advanced lesions , trucut biopsy is used to localize the ER and PR receptors by immunohistochemistry . Immunocytochemistry can be a better alternative to immunohistochemistry as it better fixes cells . AIMS To evaluate the degree of correlation between immunocytochemical ( ICC ) and immunohistochemical ( IHC ) determination of ER and PR in breast cancer . SETTING S AND DESIGN Fine needle aspiration cytology ( FNAC ) was performed on 100 primary breast cancers immunostained for ER and PR during a period of 1 year 7 months , i.e. , from January 2006 to July 2007 . MATERIAL S AND METHODS Papanicolaou-stained slides were destained , fixed in cold acetone and su bmi tted for immunocytochemistry . In the prospect i ve analysis , FNAC smears were straightaway fixed in cold acetone and su bmi tted for ER and PR . Peroxidase , antiperoxidase technique was used for immunocytochemistry . STATISTICAL ANALYSIS Spearman Rank correlation test was used . RESULTS Differences between groups were analysed and correlations were studied . Concordance for ER was 50 % and for PR was 29 % . Both ER and PR were positive in four cases : ER only in three and PR in one , and both were negative in nine cases . Use of the least best buffer and technical errors contributed to the lower ICC rate . CONCLUSION Although Immunocytochemistry removes the derogatory step of antigen deterioration , technical errors can cause hindrance in achieving the best of the results Summary The immunohistochemical demonstration of oestrogen receptor ( OR ) was performed on 32 r and omly selected and routinely processed breast carcinomas after wet autoclave pretreatment of sections . The autoclave method was compared to the OR status found on frozen sections as well as to alternative pretreatment methods such as enzymatic predigestion and microwave irradiation . Using four different monoclonal antibody clones ( H222 , LH1 , CC4 - 5 , ID5.26 ) , the OR status was evaluated for each of the various pretreatment methods applied . All cases with a high OR content on frozen sections ( n = 11 ) also showed a high OR status on wet autoclave-pretreated paraffin tissues using antibody clones 1D5.26 and CC4 - 5 ; in cases with low OR content on frozen sections , no false-negative cases were recorded using only the antibody 1D5.26 neither after wet autoclave nor microwave pretreatment . In addition , with this antibody , OR was detectable after autoclave pretreatment in two cases which were considered to be OR-negative even on frozen sections . When the primary antibody was omitted , no false-positive cases were observed after wet autoclave pretreatment . Thus , in our h and s , wet autoclave pretreatment , in combination with the antibody 1D5.26 , offers a highly sensitive method for the immunohistochemical demonstration of OR in routinely formalin-fixed , paraffin-embedded sections of breast carcinomas Background Precise preoperative profiling of breast tumors could facilitate fuller consideration of (neo)adjuvant therapies . Methods Diagnostic core biopsy ( DCB ) accuracy in profiling the primary tumor was prospect ively studied in 95 patients with operable breast cancer . The histological type and grade ( hematoxylin and eosin staining ) and membrane receptor status ( semiquantitative immunohistochemistry for estrogen [ ER ] and progesterone [ PR ] receptors , as well as Her-2 antigen expression ) were assigned by the DCB before surgery . These measures were then compared with those of the definitive surgical specimen available after operation . Results DCB correctly ascribed tumor type and grade and ER , PR , and Her-2 receptor status in most cases ( correlating exactly in 97.5 % , 77 % , 68 % , 71 % , and 60 % , respectively ) with at least moderate concordance ( weighted κ , > .41 ) . When miscategorized , DCB consistently tended to upscore the receptor stain intensity compared with the surgical specimen ( 22 % , 19 % , and 27 % had higher ER , PR , and Her-2 categorical scores , respectively ) . ER H-scores correlated best in specimens that stained strongly ( 224.4 ± 3 vs. 215.5 ± 5 ) and were significantly higher on DCB in those that stained either moderately ( 195.6 ± 8.2 vs. 156.8 ± 5.1 ; P < .0001 ) or weakly ( 157.1 ± 24.8 vs. 81.4 ± 4 ; P = .02 ) . DCB accurately identified all tumors with clinical ly important ER and Her-2 expression . Furthermore , it promoted three patients into the therapeutically significant range of ER ( n = 1 ) or Her-2 ( n = 2 ) expression . ER negativity on DCB ( n = 25 ) indicated a high- grade tumor ( 88 % ) , although 11 ( 44 % ) patients also overexpressed Her-2 . Significant Her-2 expression ( n = 16 ) on DCB predicted the tumor as being poorly differentiated ( 80 % ) and both ER and PR negative ( 67 % ) . Conclusions DCB accurately profiles clinical ly relevant measures of primary tumor cell differentiation . It also reliably categorizes patients with regard to (neo)adjuvant therapy before radical surgery is attempted Aim : To assess whether immunohistochemically stained tissue microarrays ( TMA ) of 2 mm cores from paraffin embedded tumour tissue may replace whole sections in semi-quantitative evaluation of selected potential markers for endocrine treatment . Methods : Whole sections and 2 mm cores on TMA were used for immunohistochemical staining of potential markers for endocrine treatment . The Allred scoring system was used for the markers with nuclear localisation : the oestrogen receptor , the progesterone receptor , p27 and the oestrogen receptor co-regulator amplified in breast cancer 1 ( AIB1 ) . The Allred scoring system was also used for the non-nuclear markers Bcl-2 , pS2 and cyclooxygenase 2 ( COX-2 ) ; the membrane receptors HER-2 , insulin-like growth factor I receptor ( IGF-IR ) and epidermal growth factor receptor were quantified according to the guidelines for the Herceptest . Results : The data and statistical analyses showed that the semi-quantitative evaluation of oestrogen receptor , progesterone receptor , AIB1 , COX-2 , HER-2 and IGF-IR on TMA blocks was comparable with analysis on whole sections . Conclusions : This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy . Considering the small size of many breast tumours , the speed and cost-effectiveness of immunohistochemistry on TMA compared with whole sections , and the importance of the expression level of the proteins , semi-quantitative scoring on TMA has great potential in both retrospective and prospect i ve studies aim ing at improving the prediction of response to endocrine treatment AIMS The authors have previously described quantitative , computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer . The aim of this study was to vali date the aforementioned system against the commonly used methods of assessing oestrogen receptor status . METHODS Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-alpha-oestrogen receptor monoclonal antibody ( 1D5 ) using a st and ard immunohistochemical protocol . Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software . A nuclear mask was obtained by digitally selecting the nuclear area . Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics . Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 r and omly sample d nuclei from ten high powered fields HPF . Cut off value for positivity was taken as 10 % . Cytosolic oestrogen receptor concentration was measured through enzyme immunisation . Cut off value for ER positivity was taken as 200 fmol/g ( wet tissue ) . RESULTS One hundred and fifty-six sections were studied of which 41 were ER negative . Median percentage positivity in the remainder was 90 % ( 17 - 100 ) by manual assessment . The median red scale value was 108 ( 58 - 156 ) . A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually ( P<0.0001 ) . There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration ( P<0.001 ) . CONCLUSION Oestrogen receptor positivity can be accurately assessed through digital image analysis . This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei , which express oestrogen receptors Over 250 breast carcinomas were studied in order to establish whether or not quantitative immunohistochemical assays ( ICA ) for estrogen and progesterone receptors ( ER and PR ) with computer-assisted image analysis could favorably compare with st and ard cytosolic assays . Initially , variable antigenic preservation secondary to improper tissue fixation and processing led to irregular receptor preservation and unevenly stained areas indistinguishable from true intratumor antigenic heterogeneity . As a direct consequence of the field selection s chosen for analysis , assay reproducibility was less than optimal . Proper tissue fixation and h and ling eliminated most of the irregular staining ; selection of fields to analyze became less cumbersome and more reproducible . Differences in staining intensity due to minimal variations in the ICA also result ed in difficult reproducibility . St and ardizing the technique and using an automatic stainer notably eliminated that problem . The second and equally important question was to establish if quantitative ER-ICA had relevance as a predictor for prognosis . The Kaplan-Meier product limit estimator for quantitated ER values and Cox regression for risk of mortality and disease progression were performed . The results obtained discriminated high- and low-risk groups for overall survival ( p = 0.016 ) better than the dextran-coated charcoal assay . Elimination of two major obstacles and proof of the predictive value of quantitative ICA has transformed the assay into a valid alternative to cytosolic methods ; however , before that takes place it is critical to establish st and ard procedures for both ICA and quantitation so interlaboratory variability is reduced to a minimum Two different methods to determine steroid receptors were analysed with respect to their ability to estimate prognosis in primary breast cancer patients . The immunohistochemical assay ( IHA ) was compared with the dextran-coated charcoal ( DCC ) method of receptor determination . A r and om sample of 281 patients with invasive ductal carcinoma was drawn from 841 consecutive patients with primary breast carcinoma treated at Odense University Hospital between 1 January 1980 and 31 December 1990 . Receptor determination by the DCC method had been carried out previously in 164 patients for the oestrogen receptor and in 132 patients for the progesterone receptor . The former group was reassessed by IHA with the antibody ER1D5 , and the latter with the antibody PgR-ICA . The median follow-up time was 8.3 years ( range 2.9 - 12.9 years ) . A cutoff of zero was used for the DCC method . Immunohistochemical results were quantified by counting in systematic ally r and om sample d fields of vision and values above zero were considered to be positive . Overall agreement of positive and negative cases was 86 % for the oestrogen receptor and 83 % for the progesterone receptor . Although the study included a limited number of patients , receptor positive cases fared better than negative cases in all situations . Investigation of the prognostic power revealed that classification based on IHA allowed better discrimination of patients than classification based on the DCC method . The reason for this difference might be because distinction between benign and malignant tissue is possible using the IHA method . Thus , IHA results appear to be more clinical ly relevant PURPOSE To evaluate locally versus central ly assessed estrogen ( ER ) and progesterone ( PgR ) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer . PATIENTS AND METHODS Breast International Group ( BIG ) 1 - 98 r and omly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent . The Central Pathology Office received material for 6,549 patients ( 82 % ) , of which 79 % were assessable ( 6,291 patients ) . Prognostic and predictive value of both local and central hormone receptor expression on disease-free survival ( DFS ) were evaluated among 3,650 assessable patients assigned to the monotherapy arms . Prognostic value and the treatment effect were estimated for central ly assessed ER and PgR expression levels using the Sub population Treatment Effect Pattern Plot . RESULTS Central review confirmed 97 % of tumors as hormone receptor-positive ( ER and /or PgR > or = 10 % ) . Of 105 tumors locally ER-negative , 73 were found to have more than 10 % positive cells , and eight had 1 % to 9 % . Of 6,100 tumors locally ER positive , 66 were found to have no staining , and 54 had only 1 % to 9 % . Discordance was more marked for PgR than ER . Patients with tumors reclassified central ly as ER-negative , or as hormone receptor-negative , had poor DFS . Central ly assessed ER and PgR showed prognostic value . Among patients with central ly assessed ER-expressing tumors , letrozole showed better DFS than tamoxifen , irrespective of PgR expression level . CONCLUSION Central review changed the assessment of receptor status in a substantial proportion of patients , and should be performed whenever possible in similar trials . PgR expression did not affect the relative efficacy of letrozole over tamoxifen BACKGROUND This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer . METHODS Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer . RESULTS Progesterone receptor ( PR ) discordance was 18 % . In 87 % of PR discordant cases , the image-guided biopsy was positive and the final specimen was negative ( P = 0.03 ) . Tumor grade was discordant in 36 % of patients Discordance for estrogen receptor ( ER ) = 2 % ; MIB-1 = 18 % ; Her2/neu = 9 % ; EGFR = 10 % ; p53 = 9 % ; and bcl-2 = 0 % . The discordance for these markers was r and om and did not reach statistical significance . CONCLUSION Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers . A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen . Tumor grade should be based upon the final surgical specimen whenever possible Image analysis was used to investigate the prognostic significance of immunostaining for oestrogen receptor ( ER ) , p53 tumour‐suppressor protein and tumour cell proliferation ( MIB‐1 ) in a r and om cohort of 200 primary breast cancer patients with between 4 and 7 years of clinical follow‐up . Image measurements of the percentage of immunopositive cancer cell nuclei ( % positive nuclear area ) were recorded for the above tumour features for each patient . Assessment of relative risk using Cox 's univariate analysis indicated that tumour size , number of cancer‐involved nodes , MIB‐1 and ER % positive nuclear area were significantly associated with breast cancer disease outcome , i.e. , relapse‐free survival and overall survival . In multivariate analysis , tumour size , number of involved nodes , ER and MIB‐1 % positive nuclear area were retained as independent predictors of prognosis , depending on the image measurement cut‐point used . A prognostic model , which can be used without reference to nodal involvement , was constructed for tumour size , ER cut‐point of 30 % positive nuclear area and MIB‐1 cut‐point of 10 % positive nuclear area . Kaplan‐Meier analysis of this image‐based prognostic index identified 4 risk groups with predicted 5‐year overall survival rates of 93 % , 83 % , 76.7 % and 61.5 % . We conclude that image measurements of ER and proliferative rate can be combined with tumour size to construct a prognostic index which reliably predicts disease outcome in primary breast cancer without knowledge of the nodal status of the patient . Int . J. Cancer ( Pred . Oncol . ) 84:203–208 , 1999 . © 1999 Wiley‐Liss , The aim of the present study was to compare oestrogen receptor ( ER ) analysis results obtained in cytosols of frozen breast cancer tissue ( using biochemical assay ) with those obtained in paraffin-embedded tissue ( using immunoperoxidase staining with monoclonal antibodies ( DAKO-ER , 1D5 ) , and an ER positivity cut-off level of > 10 % stained nuclei ) . In 86 % ( 84/98 ) of the sample s the same ER status ( 28 negative and 56 positive ) was obtained with both procedures . In eight cases , the paraffin section was ER positive but the corresponding cytosol sample ER negative , whereas six cases showed the opposite pattern . The ER positive subgroup manifested better outcome after adjuvant treatment than the ER negative subgroup ( p = 0.003 ( cytosol ) , and p = 0.004 ( paraffin ) ) . As compared with the percentage of stained nuclei , staining intensity yielded no additional information . Although the results of ER analysis of paraffin-embedded material seem promising , it is too early to prefer it to frozen tissue , though this would be useful when no frozen tissue is available PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen . The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from chemotherapy ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( < 18 ) tumors derived minimal , if any , benefit from chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of chemotherapy benefit This study was undertaken to evaluate our abilityto detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA)from patients with primary breast carcinomas . 147 patients with operable primary breast carcinomas who had beenrecruited to a r and omized trial of primary medicaltherapy ( PMT ) versus adjuvant chemoendocrine therapy were analysed . FNAs were taken prior to therapy and fromthis multiple slides were produced using cytospin cytocentrifugation and stored at − 80 ° C for subsequentimmunocytochemical analysis ( ICA ) . ICA was performed for oestrogenreceptor ( ER ) , progesterone receptor ( PgR ) , p53 , Ki67 , and Bcl-2 . Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction ( SPF ) . In a subgroup of50 patients who had surgery prior to systemictherapy , as well as FNAs , sections were alsotaken from paraffin-embedded blocks and stained by ICAfor ER , PgR and p53 for validation . Inthese patients ER was additionally measured by enzymeimmunoassay ( EIA ) from frozen tissue taken at surgery . ER , PgR , p53 , Bcl-2 , and Ki67 were successfullydetected by ICA while ploidy and SPF weresuccessfully measured by flow cytometry from FNA material .The percentage positive values obtained were reasonable and as follows : 74 % for ER , 70 % for PgR,36 % for p53 , 80 % for Bcl-2 . 68 % oftumours were aneuploid and 32 % diploid . Significant relationshipsbetween these measurements were observed in accordance withexpectations . The concordance for ER , PgR , and p53from FNA when compared to ICA of matchinghistological sections was 91.5 % , 75.5 % , and 75 % respectively . For ER the concordance between measurement by ICAof cytological and histological sample s and by EIAof frozen tissue was 82.5 % and 84 % respectively . These results indicate that multiple molecular markers canbe adequately tested on cytological preparations from primary breast tumours . These markers can be used todetermine prognosis and predict response to PMT Estrogen receptor ( ER ) was estimated immunohistochemically in formalin-fixed and paraffin-embedded tissue from the primary breast cancer in 349 postmenopausal patients with a high risk of recurrence and compared with the results of dextran-coated charcoal assay . There was a highly significant correlation between the ER classification obtained by the two methods ( p less than 10(-6 ) ) . Patients ER positive according to immunohistochemical estimate had a significantly longer disease-free survival ( p less than 0.001 ) and survival ( p less than 0.001 ) than ER negative patients . The DCC assay showed an advantage of ER positive patients of the same magnitude . The patients , who were followed for a median of 86 months , were a subset of 1,700 patients participating in the Danish Breast Cancer Cooperative Group 's r and omized trial of adjuvant tamoxifen ( TAM ) treatment . In the presently analyzed subset of patients there were no statistically significant difference in disease-free survival ( p = 0.52 ) or survival ( p = 0.54 ) between patients who received adjuvant TAM and the controls . The same was true for receptor-defined subgroups regardless if the ER receptor was estimated in paraffin-embedded tissue or by the dextran-coated charcoal method . The analyzed subset might have been too small for demonstrating a positive effect of adjuvant TAM treatment |
595 | 16,988,545 | In sepsis patients with DIC , administration of antithrombin concentrate may increase overall survival . | The objective was to estimate the effect of antithrombin therapy on mortality in disseminated intravascular coagulation ( DIC ) of severe sepsis and septic shock . | BACKGROUND Disseminated intravascular coagulation ( DIC ) is a serious complication of sepsis that is associated with a high mortality . OBJECTIVES Using the adapted International Society on Thrombosis and Haemostasis ( ISTH ) diagnostic scoring algorithm for DIC , we evaluated the treatment effects of high-dose antithrombin ( AT ) in patients with severe sepsis with or without DIC . PATIENTS AND METHODS From the phase III clinical trial in severe sepsis ( KyberSept ) , 563 patients were identified ( placebo , 277 ; AT , 286 ) who did not receive concomitant heparin and had sufficient data for DIC determination . RESULTS At baseline , 40.7 % of patients ( 229 of 563 ) had DIC . DIC in the placebo-treated patients was associated with an excess risk of mortality ( 28-day mortality : 40.0 % vs. 22.2 % , P < 0.01 ) . AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6 % compared with placebo ( P = 0.02 ) whereas in patients without DIC no effect on 28-day mortality was seen ( 0.1 % reduction in mortality ; P = 1.0 ) . Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo ( major bleeding rates : 7.0 % vs. 5.2 % for patients with DIC , P = 0.6 ; 9.8 % vs. 3.1 % for patients without DIC , P = 0.02 ) . CONCLUSIONS High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction . The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment Patients with fulminant hepatic failure have severe circulatory disturbances which may be due to fibrin and cellular plugs in micro-vessels which are a consequence of intravascular coagulation and which can lead to multiorgan failure . Since antithrombin III supplementation has been shown to be beneficial in animal models of septic shock with disseminated intravascular coagulation , a controlled study was performed to investigate the effect of antithrombin III supplementation in fulminant hepatic failure . Twenty-five patients in grade III or IV coma were selected on the basis of evidence of sepsis , intravascular coagulation and a high risk of developing multiorgan failure . Thirteen patients received 3000 units of antithrombin III ( Kybernin P ; Behringwerke ) , followed by a further 1000 units every 6 h. Antithrombin III activity increased from 0.26 + /- 0.04 SE U/ml to 0.82 + /- 0.07 U/ml at 3 h post infusion ( normal range 0.80 - 1.20 U/ml ) and remained greater than 0.80 U/ml throughout the study without any apparent increase in the frequency of bleeding . However , survival was not improved and markers of intravascular coagulation remained similar between the two groups . Thus , although the antithrombin III deficiency in fulminant hepatic failure can be corrected by supplementation with antithrombin III concentrate , its use in the prevention of intravascular coagulation and to avoid microvessel plugging needs to be studied at an earlier stage in the disease Objectives : To evaluate the safety , pharmacokinetics , and the practicability of two different antithrombin III ( AT III ) high-dose regimens in patients with severe sepsis.¶ Design : Prospect i ve , open , r and omized , 2 parallel groups , multinational clinical trial.¶ Setting : Eleven academic medical center intensive care units ( ICU ) in Austria , Belgium , Denmark , Germany , Norway and Sweden.¶ Patients : Thirty-three patients with severe sepsis who received st and ard supportive care and antimicrobial therapy , in addition to the administration of AT III.¶ Interventions : Patients received an intravenous loading dose of 6,000 IU AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4 h or a continuous infusion of 250 IU AT III/h for 4 days , result ing in a total dose for both dosage regimens of 30,000 IU AT III.¶ Measurements : All patients were evaluated for safety and all but one for pharmacokinetics.¶ Results and conclusions : The administration of AT III was safe and well tolerated . The overall 28-day all-cause mortality was 30 % ( 43 % intermittent bolus infusions ; 21 % continuous infusion ) . The mean probability of dying according to the SAPS II was 48 % . The difference in mortality between both groups was within the range of chance . AT III plasma levels were elevated from low baseline levels to above 120 % soon after onset of AT III therapy and remained at these levels for the treatment phase of 4 days . Functional and immunologic levels of AT III corresponded very well . With an overall median volume of distribution of 4.5 l ( range : 2.4–6.5 l ) , AT III only moderately extended beyond plasma . The overall median elimination half-life was 18.6 h ( range : 5.1–37.4 ) . Overall , median response was 1.75 % per IU/kg ( range : 1.14–2.8).¶The variability of elimination parameters was quite noteworthy ( CV = 41–59 % ) , whereas distribution-related parameters showed a moderate variability ( CV = 24 % ) . In spite of this variability , both high-dose IV regimens reliably provided AT III levels above 120 % for all but one patient . An increased mortality was observed for patients with a distribution volume exceeding 4.5 l ( or a response < 1.7 % per IU/kg ) . AT III distribution volumes above 4.5 l might indicate a capillary leak phenomenon . The continuous infusion regimen was slightly preferred by the investigators with regard to practicability Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction . Antithrombin III ( AT III ) is a natural inhibitor of thrombin , a central procoagulatory factor with pleiotropic activities . Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction . To determine whether long-term AT III supplementation has beneficial effects on organ function , we conducted a r and omized , prospect i ve study in surgical patients with severe sepsis . The study evaluated the long-term effect of AT III supplementation ( duration of treatment : 14 days ) . After r and omization ( AT III vs. control group ) , AT III was infused continuously over 14 days to obtain plasma AT III activities > 120 % . Forty consecutive patients were recruited ( 20 AT III/20 control group ) . Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period . From these 11 patients , 8 patients ( 5 AT III/3 control group ) died within 72 h due to septic shock . The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function . AT III caused a disappearance of disseminated intravascular coagulation ( DIC ) in all patients with DIC , whereas in control patients , the frequency of DIC remained constant ( p < .05 ) . In AT III patients a progressive increase in oxygenation index ( Pao2/Fio2 ratio ) and a continuous decrease in pulmonary hypertension index ( mean pulmonary artery pressure/mean arterial pressure ( PAP/MAP ) ratio ) indicated an improvement of lung function ( p < .05 vs. control ) . AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy ( p < .05 ) . Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis A prospect i ve , r and omized , controlled trial to examine the effects of antithrombin supplementation on mortality , coagulation and renal function has been carried out on 132 intensive care patients . Antithrombin activity was measured in all patients on admission to the intensive care unit ( ICU ) . Patients with an antithrombin activity of less than 70 % were r and omized to either receive antithrombin replacement or to act as controls . Antithrombin activity was maintained above 70 % in the treated patients throughout their stay on ICU . Ninety-three patients had an antithrombin activity of less than 70 % and 35 received replacement therapy . Patients with antithrombin activity below 70 % remained on the ICU significantly longer and had a significantly higher mortality rate than patients with antithrombin activity above 70 % . Antithrombin supplementation neither reduced mortality nor shortened the intensive care stay . Fifty patients with reduced antithrombin activity remained on the ICU for at least 4 days , 25 received antithrombin and 25 acted as controls ; coagulation parameters and renal function have been monitored in these patients . Fibrinogen concentration and platelet count were unaffected by antithrombin replacement . Antithrombin supplementation did not appear to reduce the incidence of impaired renal function in sepsis , trauma and postoperative patients . The creatinine clearance fell below 20 ml/min in eight patients in the no-treatment arm while by comparison only three patients in the treatment arm developed impaired renal function . Our study does not demonstrate a clear role for the use of antithrombin supplementation in intensive care , however the finding that antithrombin reduced renal impairment is encouraging and a larger study to confirm this finding is at present underway CONTEXT Activation of the coagulation system and depletion of endogenous anticoagulants are frequently found in patients with severe sepsis and septic shock . Diffuse microthrombus formation may induce organ dysfunction and lead to excess mortality in septic shock . Antithrombin III may provide protection from multiorgan failure and improve survival in severely ill patients . OBJECTIVE To determine if high-dose antithrombin III ( administered within 6 hours of onset ) would provide a survival advantage in patients with severe sepsis and septic shock . DESIGN AND SETTING Double-blind , placebo-controlled , multicenter phase 3 clinical trial in patients with severe sepsis ( the KyberSept Trial ) was conducted from March 1997 through January 2000 . PATIENTS A total of 2314 adult patients were r and omized into 2 equal groups of 1157 to receive either intravenous antithrombin III ( 30 000 IU in total over 4 days ) or a placebo ( 1 % human albumin ) . MAIN OUTCOME MEASURE All-cause mortality 28 days after initiation of study medication . RESULTS Overall mortality at 28 days in the antithrombin III treatment group was 38.9 % vs 38.7 % in the placebo group ( P = .94 ) . Secondary end points , including mortality at 56 and 90 days and survival time in the intensive care unit , did not differ between the antithrombin III and placebo groups . In the subgroup of patients who did not receive concomitant heparin during the 4-day treatment phase ( n = 698 ) , the 28-day mortality was nonsignificantly lower in the antithrombin III group ( 37.8 % ) than in the placebo group ( 43.6 % ) ( P = .08 ) . This trend became significant after 90 days ( n = 686 ; 44.9 % for antithrombin III group vs 52.5 % for placebo group ; P = .03 ) . In patients receiving antithrombin III and concomitant heparin , a significantly increased bleeding incidence was observed ( 23.8 % for antithrombin III group vs 13.5 % for placebo group ; P<.001 ) . CONCLUSIONS High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset . High-dose antithrombin III was associated with an increased risk of hemorrhage when administered with heparin . There was some evidence to suggest a treatment benefit of antithrombin III in the subgroup of patients not receiving concomitant heparin AT-III LLC , a joint venture between Genzyme Transgenics ( GTC ) and Genzyme General , is developing transgenic recombinant human antithrombin III ( rhAT-III ) as a potential treatment for sepsis and other disorders involving thrombosis . It is in phase III clinical trials in the US and Europe as an anticoagulant in patients undergoing elective cardiac surgery such as cardiopulmonary bypass Objective : Sepsis is frequently associated with coagulatory activation , which may contribute to deteriorated organ function . Antithrombin is one important endogenous coagulation inhibitor that is therapeutically applied during sepsis . This study investigates the effect of 14-day antithrombin application on coagulatory variables . Design : Prospect i ve study . Setting : Surgical intensive care unit of a university hospital . Patients : Forty patients with severe sepsis . Interventions : Patients with severe sepsis were r and omly assigned to receive either conventional intensive care treatment ( n = 20 , controls ) or antithrombin substitution that aim ed at a plasma antithrombin activity ≥120 % during a long-term ( 14-day ) study period ( n = 20 , antithrombin ) . To allow comparative analysis of laboratory variables over time , all patients who did not survive the 14-day-period ( five controls and six antithrombin patients ) were prospect ively excluded from the final evaluation . Their data were included in an intent-to-treat analysis . Measurements and Main Results : Antithrombin supplementation normalized global coagulation tests and increased prothrombin activity as well as fibrinogen concentration , reflecting less coagulation factor consumption ( percent change from baseline in prothrombin activity , p < .01 vs. controls at days 9 , 11–14 of antithrombin vs. controls [ unpaired Student ’s t-test ] ; fibrinogen concentration , p < .01 vs. controls at days 10 , 11 , 13 , and 14 of antithrombin ) . Simultaneously , antithrombin reduced contact system activation as indicated by increasing prekallikrein activities over time ( % change , p < .01 vs. controls at days 6 , 9–14 ) and increased protein C activities when compared with controls ( % change , p < .01 vs. controls at days 10–14 ) . Most changes occurred from day 7 to day 14 of antithrombin supplementation . Antithrombin did not influence C1 esterase inhibitor , plasminogen , & agr;2 antiplasmin , or platelet counts ( p > .01 ) . Conclusion : In this first study on long-term antithrombin therapy , antithrombin significantly reduced septic coagulatory response in patients with severe sepsis when given over 14 days We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose‐dependent anticoagulant properties and potentially decrease endotoxin ( lipopolysaccharide [LPS])–induced cytokine production . This was a r and omized , double‐blind , placebo‐controlled study in parallel groups enrolling 30 healthy male volunteers . The active treatment groups received infusions of recombinant human antithrombin to increase antithrombin levels to 200 % and 500 % before infusion of 2 ng/kg endotoxin ( LPS ) . Infusion of antithrombin dose‐dependently decreased coagulation ( P<.01 by repeated‐ measures ANOVA ) : peak levels of prothrombin fragment ( 1.8 nmol/L [ 95 % confidence interval ( CI ) , 1.3–2.3 nmol/L ] in the 500 % antithrombin group and 4.4 nmol/L [ 95 % CI , 2.7–6.2 nmol/L ] in the placebo group at 4 hours ) , thrombin antithrombin complexes ( 12 μg/L [ 95 % CI , 8–16 μg/L ] in the 500 % antithrombin group and 34 μg/L [ 95 % CI , 20–48 μg/L ] in the placebo group at 4 hours ) , and D‐dimer ( 0.2 μg/L [ 95 % CI , 0.1–0.2 μg/L ] in the 500 % antithrombin group and 0.5 μg/L [ 95 % CI , 0.4–0.7 μg/L ] in the placebo group ) . Recombinant human antithrombin decreased peak interleukin‐6 levels by 40 % ( 222 pg/mL [ 95 % CI , 148–295 pg/mL ] and 216 pg/mL [ 95 % CI , 112–320 pg/mL ] in the 500 % and 200 % antithrombin groups , respectively , versus 357 pg/mL [ 95 % CI , 241–474 pg/mL ] in the placebo group ; P<.001 by ANOVA ) . Finally , infusion of recombinant human antithrombin rapidly and transiently decreased neutrophil counts ( by 19 % [ 95 % CI , 8%–30 % ] in the 500 % antithrombin group versus 6 % [ 95 % CI , 1%–10 % ] in the placebo group , P = .002 by Kruskal‐Wallis ANOVA ) and monocyte counts ( by 30 % [ 95 % CI , 16%–44 % ] in the 500 % antithrombin group and 18 % [ 95 % CI , 9%‐28 % ] in the 200 % antithrombin group versus 8 % [ 95 % CI , 5%‐20 % ] in the placebo group , P = .04 ) before LPS challenge , indicating that recombinant human antithrombin directly interacts with these leukocyte subsets . In summary , recombinant human antithrombin dose‐dependently inhibited tissue factor‐triggered coagulation . Effects on leukocytes and inhibition of interleukin‐6 release seem to represent specific pharmacodynamic properties of recombinant human antithrombin Objective : To explore if patients with severe sepsis and with a predicted high risk of death ( according to the Simplified Acute Physiology Score II ) might have a treatment benefit from high-dose antithrombin III . Design : Subgroup analysis of a r and omized , placebo-controlled , double-blind , prospect i ve phase III study . Setting : Unifactorial and multifactorial re analysis of prospect ively defined population s from the KyberSept trial . Patients : We studied 1,008 patients ( 43.6 % of the overall intention-to-treat population , n = 2,314 ) with a predicted mortality rate of 30–60 % at study entry as defined by the Simplified Acute Physiology Score II . Interventions : Patients were r and omized in a 1:1 fashion to receive either high-dose antithrombin III ( 30,000 IU intravenously over the period of 4 days ) or placebo . Measurements and Main Results : In a Kaplan-Meier analysis of patients with a predicted mortality of 30–60 % , the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo ( p = .04 ) . If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III ( n = 140 ) or placebo ( n = 162 ) , the treatment effect appeared to be even more pronounced : 28-day mortality rate , 35.7 % vs. 44.4 % ( risk ratio , 0.804 ; 95 % confidence interval , 0.607–1.064 ) ; 56-day mortality rate , 39.9 % vs. 52.2 % ( risk ratio , 0.764 ; 95 % confidence interval , 0.593–0.984 ) ; 90-day mortality rate , 42.8 % vs. 55.1 % ( risk ratio , 0.776 ; 95 % confidence interval , 0.614–0.986 ) . Like in the overall population , the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo . Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications . Conclusions : Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death . This benefit may even be stronger when concomitant heparin is avoided Objective To evaluate the effect of the AT III concentrates upon the clinical evolution and hemostatic parameters . Design Prospect i ve , open , r and omized trial . Patients and participants Septic and multiple trauma patients admitted to our Intensive Care Unit . Setting Levels of AT III below 70 % were used as criteria to choose 36 patients , 20 of whom received treatment with AT III and 16 did not . Interventions AT III concentrates were administered at an initial dose of 60 U/kg followed by 10 U/kg every six hours . Results The administration of AT III neither contributes to alterations in haemostasis , nor the clinical evolution ( evaluated according to Apache II score ) . Conclusions The results suggest that the administration of AT III concentrates to critical patients with acquired low levels , but without manifest DIC , may not be justified ; although further studies on a larger population are required to establish definite conclussions Patients with diffuse peritonitis show an overall mortality of about 20 % , probably caused by the breakdown of local defence mechanisms combined with a systemic outspread of bacteria and toxins , which often results in sepsis syndrome A r and omised , prospect i ve , placebo-controlled phase III multicentre clinical trial ( KyberSept ) has been performed to test the efficacy of high-dose antithrombin therapy in patients with severe sepsis . Concomitant low-dose heparin has been routinely given in two thirds of patients for deep vein thrombosis prophylaxis . This study analyses heparin - antithrombin interactions in terms of long-term mortality , adverse events , and thromboembolic events . From a total of 2,314 patients with severe sepsis ( placebo : n = 1,157 ; antithrombin : n = 1,157 ) 1,616 patients ( placebo : 811 , antithrombin : 805 ) received heparin concomitantly with study drug ( antithrombin 30,000 IU ) over four days , whereas 698 patients ( 346 and 352 , respectively ) did not . In patients with no concomitant heparin , 28-day mortality was lower with antithrombin than with placebo ( 37.8 % vs. 43.6 % ; absolute reduction : 5.8 % ; risk ratio : 0.860 [ 0.725 - 1.019 ] ) , which increased until day-90 ( 44.9 % vs. 52.5 % ; absolute reduction : 7.6 % ; risk ratio : 0.851 [ 0.735 - 0.987 ] ) . In patients with concomitant heparin , no effect of antithrombin on mortality was seen ( 28-day mortality : 39.4 % vs. 36.6 % ; absolute increase : 2.8 % ; risk ratio : 1.08 [ 0.96 - 1.22 ] ) . Frequency of use of concomitant heparin increased during conduct of the study . Increased bleeding incidences were reported with antithrombin plus concomitant heparin as compared to antithrombin alone . Rates of thromboembolic events were similar when antithrombin was given with or without concomitant heparin . In the treatment of severe sepsis , high-dose antithrombin may sufficiently protect against development of venous thromboembolism when no concomitant heparin is given . Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin |
596 | 31,429,035 | The BCTs of social comparison , problem solving , demonstration of the behaviour , goal setting ( behaviour ) , behaviour substitution , and habit reversal , demonstrated moderate to high promise ratios .
Workplace interventions show promise for improving cardiometabolic risk markers .
The BCTs with the greatest promise of cardiometabolic risk marker improvements included social comparison , those related to individual habits , and behaviour goals . | Sedentary behaviour is a risk factor for type 2 diabetes and cardiovascular disease .
The aims of this work were to systematic ally review the effects of workplace sedentary behaviour reduction interventions on cardiometabolic risk markers ( primary aim ) and identify the active behaviour change techniques ( BCTs ) by which these interventions work ( secondary aim ) . | Background Extended sitting time at work is viewed as a crucial public health issue . Encouraging workers to st and during their office hours via the installation of st and ing desks maybe one effective option to combat this . Here , we investigate whether the installation of high desks in the workplace can induce positive changes in the amount of physical activity ( PA ) and thereby lead to subsequent improvements in anthropometric parameters . Methods Thirty-two white-collar workers ( 22 men and 10 women , mean age 44.2 ) were r and omly divided into two groups . A r and omised crossover trial was performed for 13 weeks . During the experimental period , subjects completed their office work in a st and ing position using stationary high desks ( st and ing work , SW ) for 10 hours per week or more ( SW period ) . The subjects were asked to maintain their normal sitting working habits during the control period ( CONT period ) . The primary outcome was PA , which was assessed objective ly using a triaxial accelerometer during weekdays and weekends . The secondary outcomes were anthropometric measurements . For each group and each parameter , the mean values during each period were recorded and were compared by paired t test . Results The daily total PA ( 10.2 ± 2.4 vs. 9.7 ± 2.3 METs · h/day , P = 0.043 ) , MVPA ( 4.2 ± 2.2 vs. 3.7 ± 1.8 METs · h/day , P = 0.025 ) , time spent in moderate PA ( 58.2 ± 20.7 vs. 53.4 ± 17.0 min/day , P = 0.019 ) and time spent in MVPA ( 62.8 ± 25.1 vs. 57.0 ± 20.3 min/day , P = 0.019 ) were significantly higher during the SW period compared to the CONT period . A weekdays verses weekends sub analysis revealed that these parameters were significantly higher during the SW period compared to the CONT period during weekdays only . No significant differences were noted before and after SW periods for most of the anthropometric measures , except waist circumference ( 83.7 ± 7.9 vs. 83.0 ± 7.9 cm , respectively , P = 0.007 ) . Conclusions St and ing work , via the installation of high desks , significantly increases moderate to vigorous physical activity , especially on weekdays . Trial registration UMIN-CRT , UMIN000016731 , 7th March 2015 Purpose Encouraging office workers to ‘ sit less and move more ’ encompasses two public health priorities . However , there is little evidence on the effectiveness of workplace interventions for reducing sitting , even less about the longer term effects of such interventions and still less on dual-focused interventions . This study assessed the short and mid-term impacts of a workplace web-based intervention ( Walk@WorkSpain , W@WS ; 2010 - 11 ) on self-reported sitting time , step counts and physical risk factors ( waist circumference , BMI , blood pressure ) for chronic disease . Methods Employees at six Spanish university campuses ( n=264 ; 42±10 years ; 171 female ) were r and omly assigned by worksite and campus to an Intervention ( used W@WS ; n=129 ; 87 female ) or a Comparison group ( maintained normal behavior ; n=135 ; 84 female ) . This phased , 19-week program aim ed to decrease occupational sitting time through increased incidental movement and short walks . A linear mixed model assessed changes in outcome measures between the baseline , ramping ( 8 weeks ) , maintenance ( 11 weeks ) and follow-up ( two months ) phases for Intervention versus Comparison groups . Results A significant 2 ( group ) × 2 ( program phases ) interaction was found for self-reported occupational sitting ( F[3]=7.97 , p=0.046 ) , daily step counts ( F[3]=15.68 , p=0.0013 ) and waist circumference ( F[3]=11.67 , p=0.0086 ) . The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline ( 446±126 ; 8,862±2,475 ) through ramping ( + 425±120 ; 9,345±2,435 ) , maintenance ( + 422±123 ; 9,638±3,131 ) and follow-up ( + 414±129 ; 9,786±3,205 ) . In the Comparison group , compared to baseline ( 404±106 ) , sitting time remained unchanged through ramping and maintenance , but decreased at follow-up ( -388±120 ) , while step counts diminished across all phases . The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period . Conclusions W@WS is a feasible and effective evidence -based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on “ sitting less and moving more ” Background Excessive sitting time is a risk factor for cardiovascular disease mortality and morbidity independent of physical activity . This aim of this study was to evaluate the impact of a sit-st and workstation on sitting time , and vascular , metabolic and musculoskeletal outcomes in office workers , and to investigate workstation acceptability and feasibility . Methods A two-arm , parallel-group , individually r and omised controlled trial was conducted in one organisation . Participants were asymptomatic full-time office workers aged ≥18 years . Each participant in the intervention arm had a sit-st and workstation installed on their workplace desk for 8 weeks . Participants in the control arm received no intervention . The primary outcome was workplace sitting time , assessed at 0 , 4 and 8 weeks by an ecological momentary assessment diary . Secondary behavioural , cardiometabolic and musculoskeletal outcomes were assessed . Acceptability and feasibility were assessed via question naire and interview . ANCOVA and magnitude-based inferences examined intervention effects relative to controls at 4 and 8 weeks . Participants and research ers were not blind to group allocation . Results Forty-seven participants were r and omised ( intervention n = 26 ; control n = 21 ) . Relative to the control group at 8 weeks , the intervention group had a beneficial decrease in sitting time ( −80.2 min/8-h workday ( 95 % CI = −129.0 , −31.4 ) ; p = 0.002 ) , increase in st and ing time ( 72.9 min/8-h workday ( 21.2 , 124.6 ) ; p = 0.007 ) and decrease in total cholesterol ( −0.40 mmol/L ( −0.79 , −0.003 ) ; p = 0.049 ) . No harmful changes in musculoskeletal discomfort/pain were observed relative to controls , and beneficial changes in flow-mediated dilation and diastolic blood pressure were observed . Most participants self-reported that the workstation was easy to use and their work-related productivity did not decrease when using the device . Factors that negatively influenced workstation use were workstation design , the social environment , work tasks and habits . ConclusionS hort-term use of a feasible sit-st and workstation reduced daily sitting time and led to beneficial improvements in cardiometabolic risk parameters in asymptomatic office workers . These findings imply that if the observed use of the sit-st and workstations continued over a longer duration , sit-st and workstations may have important ramifications for the prevention and reduction of cardiometabolic risk in a large proportion of the working population .Trial registration Clinical Trials.gov NCT02496507 Background Excessive time spent in sedentary behaviours ( sitting or lying with low energy expenditure ) is associated with an increased risk for type 2 diabetes , cardiovascular disease and some cancers . Desk-based office workers typically accumulate high amounts of daily sitting time , often in prolonged unbroken bouts . The St and Up Victoria study aims to determine whether a 3-month multi-component intervention in the office setting reduces workplace sitting , particularly prolonged , unbroken sitting time , and results in improvements in cardio-metabolic biomarkers and work-related outcomes , compared to usual practice . Methods / Design A two-arm cluster-r and omized controlled trial ( RCT ) , with worksites as the unit of r and omization , will be conducted in 16 worksites located in Victoria , Australia . Work units from one organisation ( Department of Human Services , Australian Government ) will be allocated to either the multi-component intervention ( organisational , environmental [ height-adjustable workstations ] , and individual behavioural strategies ) or to a usual practice control group . The recruitment target is 160 participants ( office-based workers aged 18–65 years and working at least 0.6 full time equivalent ) per arm . At each assessment ( 0- [ baseline ] , 3- [ post intervention ] , and 12-months [ follow-up ] ) , objective measurement via the activPAL3 activity monitor will be used to assess workplace : sitting time ( primary outcome ) ; prolonged sitting time ( sitting time accrued in bouts of ≥30 minutes ) ; st and ing time ; sit-to-st and transitions ; and , moving time . Additional outcomes assessed will include : non-workplace activity ; cardio-metabolic biomarkers and health indicators ( including fasting glucose , lipids and insulin ; anthropometric measures ; blood pressure ; and , musculoskeletal symptoms ) ; and , work-related outcomes ( presenteeism , absenteeism , productivity , work performance ) . Incremental cost-effectiveness and identification of both workplace and individual-level mediators and moderators of change will also be evaluated . Discussion St and Up Victoria will be the first cluster- RCT to evaluate the effectiveness of a multi-component intervention aim ed at reducing prolonged workplace sitting in office workers . Strengths include the objective measurement of activity and assessment of the intervention on markers of cardio-metabolic health . Health- and work-related benefits , as well as the cost-effectiveness of the intervention , will help to inform future occupational practice .Trial registration BACKGROUND Sedentary behavior is a risk factor for cardiometabolic disease . Regularly interrupting sedentary behavior with activity breaks may lower this risk . OBJECTIVE We compared the effects of prolonged sitting , continuous physical activity combined with prolonged sitting , and regular activity breaks on postpr and ial metabolism . DESIGN Seventy adults participated in a r and omized crossover study . The prolonged sitting intervention involved sitting for 9 h , the physical activity intervention involved walking for 30 min and then sitting , and the regular-activity-break intervention involved walking for 1 min 40 s every 30 min . Participants consumed a meal-replacement beverage at 60 , 240 , and 420 min . RESULTS The plasma incremental area under the curve ( iAUC ) for insulin differed between interventions ( overall P < 0.001 ) . Regular activity breaks lowered values by 866.7 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 506.0 , 1227.5 IU · L(-1 ) · 9 h(-1 ) ; P < 0.001 ) when compared with prolonged sitting and by 542.0 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 179.9 , 904.2 IU · L(-1 ) · 9 h(-1 ) ; P = 0.003 ) when compared with physical activity . Plasma glucose iAUC also differed between interventions ( overall P < 0.001 ) . Regular activity breaks lowered values by 18.9 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 10.0 , 28.0 mmol · L(-1 ) · 9 h(-1 ) ; P < 0.001 ) when compared with prolonged sitting and by 17.4 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 8.4 , 26.3 mmol · L(-1 ) · 9 h(-1 ) ; P < 0.001 ) when compared with physical activity . Plasma triglyceride iAUC differed between interventions ( overall P = 0.023 ) . Physical activity lowered values by 6.3 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 1.8 , 10.7 mmol · L(-1 ) · 9 h(-1 ) ; P = 0.006 ) when compared with regular activity breaks . CONCLUSION Regular activity breaks were more effective than continuous physical activity at decreasing postpr and ial glycemia and insulinemia in healthy , normal-weight adults . This trial was registered with the Australian New Zeal and Clinical Trials registry as ACTRN12610000953033 BACKGROUND Sit-st and desks reduce workplace sitting time among healthy office workers ; however , their metabolic and behavioral impact in higher risk population s remains unknown . METHODS 25 office workers with abdominal obesity were r and omized to an intervention ( sit-st and workstation ) or control group ( seated desk ) for 12 weeks . Physical activity , sedentary behavior , and cardiometabolic risk factors were assessed before and after the intervention period in both groups . RESULTS In comparison with the control group , which did not change , the intervention group experienced significant reductions in workday ( 344 ± 107 to 186 ± 101 min/day ) and total ( 645 ± 140 to 528 ± 91 min/day ) sitting time , as well as increases in workday st and ing time ( 154 ± 108 to 301 ± 101 min/day , P < .05 ) . There were no changes in sitting or st and ing time outside of work hours , steps taken each day , or any marker of cardiometabolic risk in either group ( all P > .05 ) . CONCLUSION Sit-st and desks were effective in reducing workplace sedentary behavior in an at-risk population , with no change in sedentary behavior or physical activity outside of work hours . However , these changes were not sufficient to improve markers of cardiometabolic risk in this population INTRODUCTION Office employees are exposed to hazardous levels of sedentary work . Interventions that integrate health promotion and health protection elements are needed to advance the health of sedentary workers . This study tested an integrated intervention on occupational sedentary/physical activity behaviors , cardiometabolic disease biomarkers , musculoskeletal discomfort , and work productivity . DESIGN Two-group , RCT . Data were collected between January and August 2014 . SETTING / PARTICIPANTS Overweight/obese adults working in sedentary desk jobs were r and omized to : ( 1 ) a health protection-only group ( HPO , n=27 ) ; or ( 2 ) an integrated health protection/health promotion group ( HP/HP , n=27 ) . INTERVENTION HPO participants received an ergonomic workstation optimization intervention and three e-mails/week promoting rest breaks and posture variation . HP/HP participants received the HPO intervention plus access to a seated activity permissive workstation . MAIN OUTCOME MEASURES Occupational sedentary and physical activity behaviors ( primary outcomes ) , cardiometabolic health outcomes , musculoskeletal discomfort , and work productivity ( secondary outcomes ) were measured at baseline and post-intervention ( 16 weeks ) . RESULTS The HP/HP group increased occupational light intensity physical activity over the HPO group and used the activity permissive workstations 50 minutes/work day . Significant associations were observed between activity permissive workstation adherence and improvements in several cardiometabolic biomarkers ( weight , total fat mass , resting heart rate , body fat percentage ) and work productivity outcomes ( concentration at work , days missed because of health problems ) . CONCLUSIONS The HP/HP group increased occupational physical activity and greater activity permissive workstation adherence was associated with improved health and work productivity outcomes . These findings are important for employers interested in advancing the well-being of sedentary office workers . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT02071420 Background Prolonged sitting time has been associated with adverse health outcomes . Interventions at work may contribute to reduced sitting . The objective was to test if a multicomponent work-based intervention can reduce sitting time and the number of prolonged sitting periods ( > 30 min ) , increase the number of sit-to-st and transitions and decrease waist circumference and body fat percentage among office workers . Primary outcomes were : change in sitting time , prolonged sitting periods and sit-to-st and transitions at follow-up 1 month later . Methods At four workplaces , 19 offices ( 317 workers in total ) were cluster r and omized for intervention or control . The intervention included the appointment of local ambassadors , management support , environmental changes , a lecture and a workshop . Sitting time was measured using an ActiGraph GT3X+ fixed on the thigh . Data were processed using Acti4 software providing data on time spent sitting , st and ing and doing other activities . Control participants were instructed to behave as usual . Follow-up measurements were obtained after 1 and 3 months . Results At 1 and 3 months , total sitting time was 71 ( P < 0.001 ) and 48 min ( P < 0.001 ) lower per 8-h workday in the intervention group compared with the control group . At 1 month , the number of prolonged sitting periods was lower ( -0.79/8-h workday , P < 0.001 ) and sit-to-st and transitions were higher ( + 14%/sitting hour , P = 0.001 ) in the intervention compared with the control group . After 3 months , trends persisted . The body fat percentage was lower by 0.61 percentage points ( P = 0.011 ) in the intervention group compared with the control group after 3 months . Conclusions The multicomponent workplace-based intervention was effective in reducing sitting time , prolonged sitting periods and body fat percentage , and in increasing the number of sit-to-st and transitions OBJECTIVE Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers , but intervention studies are required to investigate causality . We examined the acute effects on postpr and ial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking . RESEARCH DESIGN AND METHODS Overweight/obese adults ( n = 19 ) , aged 45–65 years , were recruited for a r and omized three-period , three-treatment acute crossover trial : 1 ) uninterrupted sitting ; 2 ) seated with 2-min bouts of light-intensity walking every 20 min ; and 3 ) seated with 2-min bouts of moderate-intensity walking every 20 min . A st and ardized test drink was provided after an initial 2-h period of uninterrupted sitting . The positive incremental area under curves ( iAUC ) for glucose and insulin ( mean [ 95 % CI ] ) for the 5 h after the test drink ( 75 g glucose , 50 g fat ) were calculated for the respective treatments . RESULTS The glucose iAUC ( mmol/L ) ⋅ h after both activity-break conditions was reduced ( light : 5.2 [ 4.1–6.6 ] ; moderate : 4.9 [ 3.8–6.1 ] ; both P < 0.01 ) compared with uninterrupted sitting ( 6.9 [ 5.5–8.7 ] ) . Insulin iAUC ( pmol/L ) ⋅ h was also reduced with both activity-break conditions ( light : 633.6 [ 552.4–727.1 ] ; moderate : 637.6 [ 555.5–731.9 ] , P < 0.0001 ) compared with uninterrupted sitting ( 828.6 [ 722.0–950.9 ] ) . CONCLUSIONS Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postpr and ial glucose and insulin levels in overweight/obese adults . This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : To evaluate the effectiveness of a 3-month treadmill desk intervention in eliciting changes in physical activity and sedentary behavior among overweight/obese office workers . Methods : A r and omized controlled trial was conducted among overweight/obese office workers ( n = 41 ; mean age = 40.1 ± 10.1 years ) at a private workplace . Participants were r and omly assigned to a shared-treadmill desk intervention ( n = 21 ) or a usual working condition control group ( n = 20 ) . Accelerometer-determined physical activity and sedentary behavior were measured before and after the intervention . Results : Compared with the control group , the intervention group increased daily steps ( 1622 steps/day ; P = 0.013 ) and light physical activity ( 1.6 minutes/hour ; P = 0.008 ) , and decreased sedentary time ( −3.6 minutes/hour ; P = 0.047 ) during working hours . Conclusions : Shared-treadmill desks in the workplace can be effective at promoting favorable changes in light physical activity ( specifically 40 to 99 steps/minute ) and sedentary behavior among overweight/obese office workers Objectives To test the efficacy of a multicomponent technology intervention for reducing daily sedentary time and improving cardiometabolic disease risk among sedentary , overweight university employees . Design Blinded , r and omised controlled trial . Setting A large south-eastern university in the USA . Participants 49 middle-aged , primarily female , sedentary and overweight adults working in sedentary jobs enrolled in the study . A total of 40 participants completed the study . Interventions Participants were r and omised to either : ( 1 ) an intervention group ( N=23 ; 47.6 + 9.9 years ; 94.1 % female ; 33.2 + 4.5 kg/m2 ) ; ( 2 ) or wait-list control group ( N=17 ; 42.6 + 8.9 years ; 86.9 % female ; 31.7 + 4.9 kg/m2 ) . The intervention group received a theory-based , internet-delivered programme , a portable pedal machine at work and a pedometer for 12 weeks . The wait-list control group maintained their behaviours for 12 weeks . Outcome measures Primary ( sedentary and physical activity behaviour measured objective ly through StepWatch ) and secondary ( heart rate , blood pressure , height , weight , waist circumference , per cent body fat , cardiorespiratory fitness , fasting lipids ) outcomes were measured at baseline and postintervention ( 12 weeks ) . Exploratory outcomes including intervention compliance and process evaluation measures were also assessed postintervention . Results Compared to controls , the intervention group reduced daily sedentary time ( mean change ( 95%CI ) : −58.7 min/day ( −118.4 to 0.99 ; p<0.01 ) ) after adjusting for baseline values and monitor wear time . Intervention participants logged on to the website 71.3 % of all intervention days , used the pedal machine 37.7 % of all working intervention days and pedalled an average of 31.1 min/day . Conclusions These findings suggest that the intervention was engaging and result ed in reductions in daily sedentary time among full-time sedentary employees . These findings hold public health significance due to the growing number of sedentary jobs and the potential of these technologies in large-scale worksite programmes . Trial Registration Clinical Trials.gov # NCT01371084 Developing interventions to reduce sedentary behavior in the workplace is an important public health priority . Furthermore , research is needed to determine whether different approaches to breaking up prolonged sitting during the workday are equally feasible and effective . Thus , the purpose of this study was to determine whether varying the frequency and duration of activity breaks during the workday would differentially impact sedentary behavior and health outcomes . Inactive females ( N = 49 ) working full-time sedentary jobs were recruited for this parallel-group r and omized trial . Participants were r and omly assigned to take short , frequent breaks from sitting ( 1–2 min every half hour ; SB ) or longer , planned breaks from sitting ( two 15-minute breaks per workday ; LB ) during each workday across an 8-week intervention . Sedentary time and health outcomes were assessed at baseline and post-intervention . The study ran from March 2014–June 2015 . Results showed sedentary time during the workday decreased significantly in the SB group ( − 35.6 min ; d = − 0.75 ; p = 0.03 ) , but did not change in the LB group ( + 4.5 min ; d = 0.12 ) . Participants in the SB group also demonstrated small-to-moderate declines in total cholesterol ( d = − 0.33 ; p = 0.10 ) , triglycerides ( d = − 0.38 ; p = 0.06 ) and fasting blood glucose ( d = − 0.29 ; p = 0.01 ) from pre to post-intervention . Health outcomes did not change in the LB group . This study demonstrated that taking short , frequent breaks from sitting during the workday is a feasible and effective approach for reducing sedentary time at work . These results have implication s for the development of public health messages addressing sedentary behavior , and inform future interventions to reduce sedentary time in the workplace . Trial registration This study is registered at www . clinical trials.gov : NCT02609438 Objective : To evaluate the effect of a workplace health intervention design ed to reduce prolonged occupational sitting on the mean arterial pressure ( MAP ) of desk-based employees . Methods : This r and omized controlled trial involved an experimental group who received an e-health intervention and a control group who did not . The 13-week intervention passively prompted participants to st and and engage in short bouts of office-based physical activity by interrupting prolonged occupational sitting time periodically throughout the workday . Mean arterial pressure was measured at pretest and posttest . Results : Between pretest and posttest the experimental group significantly reduced their MAP , whereas MAP in the control group did not . Conclusions : A workplace e-health intervention design ed to reduce prolonged occupational sitting was effective in decreasing MAP in desk-based employees Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk , independent of the performance of exercise . We hypothesized that a daily bout of exercise can not compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids . Methodology /Principal Findings Eighteen healthy subjects , age 21±2 year , BMI 22.6±2.6 kgm−2 followed r and omly three physical activity regimes for four days . Participants were instructed to sit 14 hr/day ( sitting regime ) ; to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr ( exercise regime ) ; to substitute 6 hrs sitting with 4 hr walking and 2 hr st and ing ( minimal intensity physical activity ( PA ) regime ) . The sitting and exercise regime had comparable numbers of sitting hours ; the exercise and minimal intensity PA regime had the same daily energy expenditure . PA was assessed continuously by an activity monitor ( ActivPAL ) and a diary . Measurements of insulin sensitivity ( oral glucose tolerance test , OGTT ) and plasma lipids were performed in the fasting state , the morning after the 4 days of each regime . In the sitting regime , daily energy expenditure was about 500 kcal lower than in both other regimes . Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml , respectively . Triglycerides , non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise . Conclusions One hour of daily physical exercise can not compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting . Reducing inactivity by increasing the time spent walking/st and ing is more effective than one hour of physical exercise , when energy expenditure is kept constant Breaking up periods of prolonged sitting can negate harmful metabolic effects but the influence on appetite and gut hormones is not understood and is investigated in this study . Thirteen sedentary ( 7 female ) participants undertook three 5-h trials in r and om order : ( i ) uninterrupted sitting ( SIT ) , ( ii ) seated with 2-min bouts of light-intensity walking every 20 min ( SIT + LA ) , and ( iii ) seated with 2-min bouts of moderate-intensity walking every 20 min ( SIT + MA ) . A st and ardised test drink was provided at the start of each trial and an ad libitum pasta test meal provided at the end of each trial . Subjective appetite ratings and plasma acylated ghrelin , peptide YY , insulin , and glucose were measured at regular intervals . Area under the curve ( AUC ) was calculated for each variable . AUC values for appetite and gut hormone concentrations were unaffected in the activity breaks conditions compared with uninterrupted sitting ( linear mixed modelling : p > 0.05 ) . Glucose AUC was lower in SIT + MA than in SIT + LA ( p = 0.004 ) and SIT ( p = 0.055 ) . There was no difference in absolute ad libitum energy intake between conditions ( p > 0.05 ) ; however , relative energy intake was lower in SIT + LA ( 39 % ; p = 0.011 ) and SIT + MA ( 120 % ; p < 0.001 ) than in SIT . In conclusion , breaking up prolonged sitting does not alter appetite and gut hormone responses to a meal over a 5-h period . Increased energy expenditure from activity breaks could promote an energy deficit that is not compensated for in a subsequent meal OBJECTIVE This study aims to evaluate the effectiveness of a draft occupational health guideline , aim ed at preventing weight gain , on employees ' body weight-related outcomes , cardiovascular disease ( CVD ) risk factors , and quality of life . METHODS In a cluster r and omized controlled trial including 16 occupational physicians ( OP ) and 523 employees , guideline -based care was compared to usual care by OP between 2009 - 2011 in the Netherl and s. Guideline -based care consisted of ( i ) providing advice to employers on how to assess and intervene on the obesogenic work environment , ( ii ) conducting five face-to-face behavioral change counseling sessions with employees to improve their lifestyles , and ( iii ) evaluating the outcome and maintaining sections i and ii . Data were collected at baseline and 6 , 12 , and 18-months follow-up . To evaluate the effects of the intervention , multilevel analyses were performed . RESULTS No significant differences were found between the intervention and control group on waist circumference [ β 1.2 cm , 95 % confidence interval ( 95 % CI ) -0.6 - 2.9 ] , body weight ( β 0.3 kg , 95 % CI -1.0 - 1.6 ) , body mass index ( β 0.1 kg/m ( 2 ) , 95 % CI -0.3 - 0.5 ) , systolic blood pressure ( β 1.7 mmHG , 95 % CI -2.4 - 5.8 ) , diastolic blood pressure ( β 0.3 mmHG , 95 % CI -1.0 - 0.6 ) , cholesterol ( β 0 mmol/l , 95 % CI -0.2 - 0.2 ) , or quality of life indicators after 18-months follow-up . Stratified analyses showed an increase in waist circumference among men ( β 2.5 cm , 95 % CI 0.5 - 4.5 ) and obese intervention participants ( β 2.7 cm , 95 % CI 0.6 - 4.7 ) compared to control participants . CONCLUSION The draft occupational health guideline was not more effective than usual care . Therefore , the guideline in its current form can not be recommended for implementation PURPOSE Sitting at work is an emerging occupational health risk . Few instruments design ed for use in population -based research measure occupational sitting and st and ing as distinct behaviors . This study aim ed to develop and vali date brief measure of occupational sitting and physical activity . METHODS A convenience sample ( n = 99 , 61 % female ) was recruited from two medium-sized workplaces and by word-of-mouth in Sydney , Australia . Participants completed the newly developed Occupational Sitting and Physical Activity Question naire ( OSPAQ ) and a modified version of the MONICA Optional Study on Physical Activity Question naire ( modified MOSPA-Q ) twice , 1 wk apart . Participants also wore an ActiGraph accelerometer for the 7 d in between the test and retest . Analyses determined test-retest reliability with intraclass correlation coefficients and assessed criterion validity against accelerometers using the Spearman ρ . RESULTS The test-retest intraclass correlation coefficients for occupational sitting , st and ing , and walking for OSPAQ ranged from 0.73 to 0.90 , while that for the modified MOSPA-Q ranged from 0.54 to 0.89 . Comparison of sitting measures with accelerometers showed higher Spearman correlations for the OSPAQ ( r = 0.65 ) than for the modified MOSPA-Q ( r = 0.52 ) . Criterion validity correlations for occupational st and ing and walking measures were comparable for both instruments with accelerometers ( st and ing : r = 0.49 ; walking : r = 0.27 - 0.29 ) . CONCLUSIONS The OSPAQ has excellent test-retest reliability and moderate validity for estimating time spent sitting and st and ing at work and is comparable to existing occupational physical activity measures for assessing time spent walking at work . The OSPAQ brief instrument measures sitting and st and ing at work as distinct behaviors and would be especially suitable in national health surveys , prospect i ve cohort studies , and other studies that are limited by space constraints for question naire items Background Measuring physical activity ( PA ) and sedentary time ( ST ) by self-report or device as well as assessing related health factors may alter those behaviors . Thus , in intervention trials assessment s may bias intervention effects . The aim of our study was to examine whether leisure-time PA , transport-related PA , and overall ST measured via self-report vary after assessment s and whether a brief tailored letter intervention has an additional effect . Methods Among a sample of subjects with no history of myocardial infa rct ion , stroke , or vascular intervention , a number of 175 individuals participated in a study comprising multiple repeated assessment s. Of those , 153 were analyzed ( mean age 54.5 years , st and ard deviation = 6.2 ; 64 % women ) . At baseline , participants attended a cardiovascular examination ( st and ardized measurement of blood pressure and waist circumference , blood sample taking ) and wore an accelerometer for seven days . At baseline and after 1 , 6 , and 12 months , participants completed the International Physical Activity Question naire . A r and om sub sample received a tailored counseling letter intervention at month 1 , 3 , and 4 . Changes in PA and ST from baseline to 12-month follow-up were analyzed using r and om-effects modelling . Results From baseline to 1-month assessment , leisure-time PA did not change ( Incidence rate ratio = 1.13 , p = .432 ) , transport-related PA increased ( Incidence rate ratio = 1.45 , p = .023 ) , and overall ST tended to decrease ( b = − 1.96 , p = .060 ) . Further , overall ST decreased from month 6 to month 12 ( b = − 0.52 , p = .037 ) . Time trends of the intervention group did not differ significantly from those of the assessment -only group . Conclusions Results suggest an effect of measurements on PA and ST . Data of r and om-effects modelling results revealed an increase of transport-related PA after baseline to 1-month assessment . Decreases in overall ST may result from repeated assessment s. A brief tailored letter intervention seemed to have no additional effect . Thus , measurement effects should be considered when planning intervention studies and interpreting intervention effects . Trial registration Clinical Trials.gov NCT02990039 . Registered 7 December 2016 . Retrospectively registered OBJECTIVE To investigate the short-term efficacy of a multicomponent intervention to reduce office workers ' sitting time . METHODS Allocation for this non-r and omized controlled trial ( n=43 participants ; 56 % women ; 26 - 62 years ; Melbourne , Australia ) was by office floor , with data collected during July-September 2011 . The 4-week intervention emphasized three key messages : " St and Up , Sit Less , Move More " and comprised organizational , environmental , and individual elements . Changes in minutes/day at the workplace spent sitting ( primary outcome ) , in prolonged sitting ( sitting time accumulated in bouts ≥ 30 min ) , st and ing , and moving were objective ly measured ( activPAL3 ) . RESULTS Relative to the controls , the intervention group significantly reduced workplace sitting time ( mean change [ 95%CI ] : -125 [ -161 , -89 ] min/8-h workday ) , with changes primarily driven by a reduction in prolonged sitting time ( -73 [ -108 , -40 ] min/8-h workday ) . Workplace sitting was almost exclusively replaced by st and ing ( + 127 [ + 92 , + 162 ] min/8-h workday ) with non-significant changes to stepping time ( -2 [ -7 , + 4 ] min/8-h workday ) and number of steps ( -70 [ -350 , 210 ] ) . CONCLUSIONS This multicomponent workplace intervention demonstrated that substantial reductions in sitting time are achievable in an office setting . Larger studies with longer timeframes are needed to assess sustainability of these changes , as well as their potential longer-term impacts on health and work-related outcomes The importance of adequate intervention descriptions in minimising research waste and improving research usability and reproducibility has gained attention in the past few years . Nearly all focus to date has been on intervention reporting in r and omised trials . Yet clinicians are encouraged to use systematic review s , whenever available , rather than single trials to inform their practice . This article explores the problem and implication s of incomplete intervention details during the planning , conduct , and reporting of systematic review s and makes recommendations for review authors , peer review ers , and journal OBJECTIVE Sit-st and workstations may result in significant reductions in workplace sitting . However , few studies have examined long-term maintenance under real-world conditions . The purpose of this study was to evaluate workplace sitting time , cardio-metabolic biomarkers , and work productivity during a workplace re- design which included the installation of sit-st and workstations . DESIGN Natural experiment with appropriately matched comparison . METHODS Office workers from distinct worksites in the same unit were recruited ( Intervention , n=24 ; Comparison , n=12 ) . Intervention arm participants received a sit-st and workstation and 4 months of sitting-specific motivational support . The comparison arm received 4 months of ergonomic focused motivational support . Time spent in sitting , st and ing , and other physical activity were measured by activPAL3c for a week . Cardio-metabolic biomarkers and work productivity were also measured . Assessment s occurred at baseline , 4 months , and 18 months . RESULTS At 4 months , work sitting time was reduced by 56.7±89.1min/8h workday ( d=-0.64 ) , relative to comparison . St and ing time ( 37.4±69.2min/8h workday ; d=0.54 ) and sit-to-st and transitions ( 3.3±0.4min/8h workday , d=0.44 ) were also improved relative to comparison . At 18 months , work sitting time reductions ( 52.6±68.3min/8h workday ; d=-0.77 ) and st and ing time improvements ( 17.7±54.8min/8h workday , d=0.32 ) were maintained in the intervention group relative to comparison . Cardio-metabolic and work productivity changes were mixed ; however , strongest effects favoring the intervention group were observed at 18 months . CONCLUSIONS Sit-st and workstations , accompanied with behavioral support , were effective in reducing workplace and overall daily sitting and increasing st and ing time in a real-world setting . The effect appears to have been sustained for 18 months , with mixed results in cardio-metabolic and productivity outcomes Objective To evaluate the effectiveness of a draft occupational health practice guideline aim ed at preventing weight gain on employees ' physical activity , sedentary behaviour and dietary behaviour and on body weight-related outcomes . Methods A r and omised controlled trial was performed comparing guideline -based care to usual care among 16 occupational physicians and 523 employees in the Netherl and s between 2009 and 2011 . Occupational physicians in the intervention group followed the draft guideline by providing advice to employers on how to assess and intervene on the obesogenic work environment and conducted five face-to-face behavioural change counselling sessions with employees to improve their lifestyle . Data of employees were collected by question naire and physical measurements at baseline and 6-months follow-up . Linear and logistic regression analyses were performed to determine effects . Results The intervention showed significant effects on sedentary behaviour at work ( β −28 min/day , 95 % CI −2 to −54 ) and on fruit intake ( β 2.1 pieces/week ; 95 % CI 0.6 to 3.6 ) . No significant intervention effects were found for physical activity , sedentary behaviour in leisure time or during weekend days , snack intake and body weight-related outcomes . Conclusion Guideline -based care result ed in a more favourable sedentary behaviour at work and increased fruit intake but did not improve employees ' physical activity , snack intake or body weight-related outcomes . Trial registration number IS RCT N/73545254 and NTR/1190 Objective : The aim of this study was to investigate the efficacy of a work-based multicomponent intervention to reduce office workers ’ sitting time . Methods : Offices ( n = 12 ; 89 workers ) were r and omized into an 8-week intervention ( n = 48 ) incorporating organizational , individual , and environmental elements or control arm . Sitting time , physical activity , and cardiometabolic health were measured at baseline and after the intervention . Results : Linear mixed modelling revealed no significant change in workplace sitting time , but changes in workplace prolonged sitting time ( -39 min/shift ) , sit-upright transitions ( 7.8 per shift ) , and stepping time ( 12 min/shift ) at follow-up were observed , in favor of the intervention group ( P < 0.001 ) . Results for cardiometabolic health markers were mixed . Conclusion : This short multicomponent workplace intervention was successful in reducing prolonged sitting and increasing physical activity in the workplace , although total sitting time was not reduced and the impact on cardiometabolic health was minimal Increased prevalence of obesity may be due to an increase of being sedentary at work . Increasing non-exercise activity thermogenesis ( NEAT ) using walking workstations may increase total physical activity and promote a leaner physical body composition ( or phenotype ) . The purpose of this study was to test whether walking slowly during work was sufficient to promote a leaner phenotype by increasing physical activity in sedentary desk workers without inducing compensation or a decrease in activity or energy expenditure during the nonworking hours . We conducted a prospect i ve cohort study using a within-subjects crossover design . The design involved two phases each lasting 2 weeks : a treadmill exercise phase in which subjects used a walking workstation for 2.5 hours a day 5 days/week and a control phase in which subjects maintained their normal work activity . Twenty-five sedentary adults working at the Minneapolis VA Health Care System . We measured body weight , body composition , food intake , 24-hour physical activity , and self-reported physical activity with the International Physical Activity Question naire ( IPAQ ) . Treadmill exercise caused a leaner phenotype ( lean mass gain and fat mass loss ) and significantly increased their 24-hour physical activity . Walking workstation use had favorable effects on physical well-being and mental focus and did not adversely affect productivity . Light treadmill exercise during work can increase physical activity and result in a leaner body composition . This is a potentially useful intervention to increase NEAT in the modern sedentary work environment BACKGROUND Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices , but long-term effects are unknown . We therefore investigated whether treadmill workstations in offices increased daily walking time . METHODS We did a r and omised controlled trial of healthy office workers who were either overweight or obese . We recruited participants from 13 different companies , which comprised 17 offices , in Umeå , Sweden . We included people who were aged 40 - 67 years , had sedentary work tasks , and had a body-mass index ( BMI ) between 25 kg/m2 and 40 kg/m2 . After the baseline measurement , we stratified participants by their BMI ( 25 - 30 kg/m2 and > 30 to 40 kg/m2 ) ; subsequently , an external statistician r and omly assigned these participants ( 1:1 ) to either the intervention group ( who received treadmill workstations for optional use ) or the control group ( who continued to work at their sit-st and desks as usual ) . Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period . Research ers were masked to group assignment until after analysis of the primary outcome . After the baseline measurement , participants were not masked to group belongings . The primary outcome was total daily walking time at weekdays and weekends , measured at baseline , 2 months , 6 months , 10 months , and 13 months with the accelerometer activPAL ( PAL Technologies , Glasgow , UK ) , which was worn on the thigh of participants for 24 h a day for 7 consecutive days . We used an intention-to-treat approach for our analyses . This trial is registered with Clinical Trials.gov , number NCT01997970 , and is closed to new participants . FINDINGS Between Nov 1 , 2013 , and June 30 , 2014 , a total of 80 participants were recruited and enrolled ( n=40 in both the intervention and control groups ) . Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min ( 95 % CI 9 to 26 ) in the intervention group and 1 min ( -7 to 9 ) in the control group ( difference 22 min [ 95 % CI 7 to 37 ] , pinteraction=0·00045 ) ; for weekend walking , the change from baseline to 13 months was 5 min (-8 to 18 ) in the intervention group and 8 min ( -5 to 21 ) in the control group ( difference -1 min [ -19 to 17 ] ; pinteraction=0·00045 ) . Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group , so the primary outcome of the trial was not met . One adverse event was reported in a participant who accidently stepped on their Achilles tendon . INTERPRETATION In a sedentary work environment , treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time . Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity . FUNDING Umeå University , the Västerbotten County Council , and the Mayo Clinic Foundation for Research OBJECTIVES To explore the effects of breaking up prolonged sitting time with st and ing or light-intensity walking on a range of cardiometabolic risk markers . DESIGN A r and omised three-period , three-treatment acute crossover trial . METHODS Ten non-obese adults took part in three trials : ( 1 ) uninterrupted sitting ; ( 2 ) seated with 2-min bouts of st and ing every 20 min ; and ( 3 ) seated with 2-min bouts of light-intensity walking every 20 min . Two st and ardised test drinks ( total 80.3 carbohydrate , 50 g fat ) were provided after an initial 1-h period of uninterrupted sitting . Plasma glucose and blood pressure were assessed hourly to calculate area under the curve . Total cholesterol , HDL , and triglycerides were assessed at baseline and 5-h . ANOVAs were used to explore between-trial differences . RESULTS Glucose area under the curve was lower in the activity-break condition compared to the uninterrupted sitting and st and ing-break conditions : mean area under the curve 18.5 ( 95 % CI 17 , 20 ) , 22.0 ( 20.5 , 23.5 ) , and 22.2 ( 20.7 , 23.7 ) mmol L/5-h , respectively , p<0.001 ; no difference between uninterrupted sitting and st and ing-break conditions ( p>0.05 ) . Systolic and diastolic blood pressure area under the curve did not differ significantly between conditions , nor did responses in lipid parameters ( p>0.05 ) . CONCLUSIONS This study suggests that interrupting sitting time with frequent brief bouts of light-intensity activity , but not st and ing , imparts beneficial postpr and ial responses that may enhance cardiometabolic health . These findings may have importance in the design of effective interventions to reduce cardiometabolic disease risk Health behaviors , including physical activity ( PA ) , of registered nurses ( RNs ) and medical assistants ( MAs ) are suboptimal but may improve with worksite programs . Using a repeated- measures crossover design , the authors explored if integrating a 6-month worksite non-exercise activity thermogenesis ( NEAT ) intervention , with and without personalized health coaching via text messaging into workflow could positively affect sedentary time , PA , and body composition of nursing staff without jeopardizing work productivity . Two ambulatory clinics were r and omly assigned to an environmental NEAT intervention plus a mobile text message coaching for either the first 3 months ( early texting group , n = 27 ) or the last 3 months ( delayed texting group , n = 13 ) , with baseline 3-month and 6-month measurements . Sedentary and PA levels , fat mass , and weight improved for both groups , significantly only for the early text group . Productivity did not decline for either group . This worksite intervention is feasible and may benefit nursing staff |
597 | 28,700,091 | There is no high- quality evidence to support or refute the use of NSAIDs alone or in combination with opioids for the three steps of the three-step WHO cancer pain ladder .
There is very low- quality evidence that some people with moderate or severe cancer pain can obtain substantial levels of benefit within one or two weeks | BACKGROUND Pain is a common symptom with cancer , and 30 % to 50 % of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life .
Non-opioid drugs are commonly used to treat cancer pain , and are recommended for this purpose in the World Health Organization ( WHO ) cancer pain treatment ladder , either alone or in combination with opioids .
A previous Cochrane review that examined the evidence for nonsteroidal anti-inflammatory drugs ( NSAIDs ) or paracetamol , alone or combined with opioids , for cancer pain was withdrawn in 2015 because it was out of date ; the date of the last search was 2005 .
This review , and another on paracetamol , up date s the evidence .
OBJECTIVES To assess the efficacy of oral NSAIDs for cancer pain in adults , and the adverse events reported during their use in clinical trials . | In a clinical double-blind study , the analgesic efficacy and the side-effects of nimesulide ( Aulin , CAS 51803 - 78 - 2 ) and naproxen administered to 68 patients affected by advanced cancer pain were compared . Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO . The dose administered was 200 mg b.i.d . ( every 12 h ) for nimesulide and 500 mg b.i.d . ( every 12 h ) for naproxen . From this study the analgesic effect and the tolerability of the two drugs appeared to be similar . Both drugs result ed to be effective with a low incidence of adverse events that may be related to their use The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel r and omized study . Ketorolac was administered intramuscularly in doses of 10 , 30 or 90 mg . Pain intensity and pain relief were assessed for 6 hours by scoring st and ard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study . Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference ( SPID ) but no difference was seen between the three ketorolac regimens . When the ketorolac groups are combined , there was a significantly better pain relief as compared to placebo . The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group . A total of 15 patients reported minor adverse events , 10 being after ketorolac doses . This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain , and are associated with a low incidence of side-effects Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size The role of non-steroidal anti-inflammatory drugs ( NSAIDs ) in cancer pain has been well established in the treatment of mild pain and in association with opioids in the treatment of moderate to severe pain . The aim of this study was to verify the effects of NSAIDs on morphine escalation in advanced cancer patients with pain followed-up at home and to assess the pharmacoeconomic implication s. A prospect i ve r and omised controlled study was carried out in 156 consecutive advanced cancer patients with pain followed-up at home in the period December 1999-December 2000 . In this group of patients , 47 were selected with pain progression after 1 week of opioid stabilisation . Patients were r and omly assigned to one of two groups : group ' O ' patients were treated with continuing opioid escalation according to their clinical needs ; group ' OK ' received ketorolac 60 mg/daily orally ( p.o . ) in three doses and then continued opioid escalation according to their clinical situation . Performance status , doses of morphine before and after starting treatment , mean weekly pain intensity ( assessed by means of a numerical scale from 0 to 10 ) , mean weekly symptoms intensity , adverse effects and pain mechanisms were recorded . Moreover , drug costs per day in both groups were calculated . Patients who received ketorolac in addition to morphine showed a better analgesia after a week in comparison to the group treated with morphine only ( P=0.005 ) . Thereafter , morphine escalation was slower and the maximum morphine dose was lower in the group treated with ketorolac . The incidence and the severity of gastric discomfort was more evident in patients treated with ketorolac , while constipation was significantly increased in patients who received morphine only . Drug costs per day were similar in both groups ; statistical differences were observed in patients who started on lower morphine doses ( < 100 mg/daily ) in the two groups ( 4.3 in the ketorolac-morphine group versus 3.4 in the morphine group ; P=0.012 ) . The use of NSAIDs reduces the need for an opioid dose escalation or allows the use of lower doses . Their use is associated with a more intense gastric discomfort , but results in less opioid-related constipation . The eventual additive cost for NSAIDs therapy is negligible , especially in patients taking high doses of morphine & NA ; A prospect i ve double‐blind r and omized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone ( 50 mg q.i.d . ) or in combination with a weak opioid ( codeine 40 mg q.i.d . ) , or with an anti‐depressant ( imipramine , 10 or 25 mg t.i.d . ) . All demographic and clinical characteristics including cancer type , presence of bone metastases , baseline pain severity , neuropathic and nociceptive pain , and depressive state , were well balanced between the three treatment groups . The main analysis of the study was on the VAS scores at visit 2 ( day 4 ) . The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac . Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy , while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events . In conclusion , in a short‐term evaluation the addition of a tricyclic anti‐depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone In a controlled double blind study of analgesics for the pain of gastrointestinal cancer , aspirin ( 650 mg ) was significantly more effective than placebo and superior to orally used codeine sulfate ( 60 mg ) . The effectiveness of aspirin was not specific for carcinoma of the pancreas , however , because the same pattern of pain relief was found in colonic carcinoma BACKGROUND Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner . This study was design ed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer , a nitric oxide donor , as coadjuvants to oral morphine in cancer pain therapy . METHODS After institutional approval and informed patient consent were obtained , 60 patients with cancer pain were r and omized to one of four groups ( n = 15 ) and studied prospect ively to evaluate analgesia and any adverse effects . A visual analog scale that consisted of a 10-cm line with 0 representing " no pain at all " and 10 representing " the worst possible pain " was introduced . All patients were regularly taking oral amitriptyline 50 mg at bedtime . The morphine regimen was adjusted individually to a maximal oral dose of 80 - 90 mg/day to keep the visual analog scale score less than 4 . When patients reported pain ( visual analog scale of 4 or more ) , despite taking 80 - 90 mg oral morphine daily , the test drug was added as follows : the control group ( CG ) received an additional 20 mg oral morphine ( 10 mg at 12-h intervals ) ; the nitroglycerin group ( NG ) received a 5-mg nitroglycerin patch daily ; the ketamine group ( KG ) received 0.5 mg/kg oral ketamine at 12-h intervals ; and the dipyrone group ( DG ) received 500 mg oral dipyrone at 6-h intervals . Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4 . RESULTS The groups were similar with respect to demographic data and visual analog scale pain scores before treatment . The visual analog scale scores after the test drug was introduced were similar among the groups . The daily consumption of oral morphine was as follows : on day 15 : CG = DG = NG ( P > 0.05 ) , CG > KG ( P = 0.036 ) ; on day 20 : CG > NG = KG ( P < 0.02 ) ( CG > KG , P < 0.005 ; CG > NG , P < 0.02 ) , DG > KG ( P < 0.05 ) ; on day 30 : CG = DG > KG = NG ( P < 0.05 ) . Patients in the CG and DG groups reported somnolence , but patients in the NG and KG groups did not . CONCLUSIONS Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics . In conjunction with their opioid tolerance-sparing function , joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management Introduction Adjunct nonopioid analgesics may improve pain control in patients with cancer needing morphine or its derivates . Dypirone is a cheap nonopioid analgesic widely used in many countries . Objective The objective of the study was to evaluate , whenever morphine was started , if associating dipyrone with it would improve pain control and if this effect was time dependent . Material s and methods This is a double-blind placebo-controlled r and omized crossover study . Thirty-four ambulatory cancer patients experiencing cancer-related pain for which oral morphine was to be started at the dose of 10 mg orally ( PO ) every 4 h were r and omized to take either dipyrone 500 mg PO every 6 h or placebo . After 48 h , patients would be switched from dipyrone to placebo and vice versa . Pain was the primary outcome and was measured using a visual analogue scale before starting medications , at 48 and 96 h. Results We r and omized 16 patients to start with placebo ( group 1 ) and 18 with dipyrone ( group 2 ) . Pain scores for groups 1 and 2 were at baseline : 7.31 ± 0.29 vs 6.88 ± 0.28 ( p = 0.3 ) , at 48 h : 7.06 ± 0.32 vs 5.5 ± 0.31 ( p = 0.001 ) , and at 96 h : 3.18 ± 0.39 vs 1.94 ± 0.37 ( p = 0.03 ) . Both groups had significant improvements in pain scores after introducing dipyrone ( p < 0.001 , for both ) . Main toxicities were nausea , vomiting , epigastric pain , and myalgias . Twenty-eight patients chose dipyrone , four placebo , and two were indifferent . Conclusions We conclude that dipyrone adds significantly to the analgesic effect of morphine and , when given at the time of starting morphine , results in better pain scores even after dipyrone is discontinued Summary The analgesic efficacy and tolerability of nimesulide and naproxen were compared in 68 patients with advanced cancer who needed to be treated with nonsteroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO . Patients received either nimesulide 200 mg or naproxen 500 mg twice daily . The analgesic efficacy and tolerability of the 2 drugs appeared to be similar . Both drugs were effective and were associated with a low incidence of adverse reactions BACKGROUND The European Pain in Cancer survey sought to increase underst and ing of cancer-related pain and treatment across Europe . PATIENTS AND METHODS Patients with all stages of cancer participated in a two-phase telephone survey conducted in 11 European countries and Israel in 2006 - 2007 . The survey screened for patients experiencing pain at least weekly , then r and omly selected adult patients with pain of at least moderate intensity occurring several times per week for the last month completed a detailed attitudinal question naire . RESULTS Of 5084 adult patients contacted , 56 % suffered moderate-to-severe pain at least monthly . Of 573 patients r and omly selected for the second survey phase , 77 % were receiving prescription-only analgesics , with 41 % taking strong opioids either alone or with other drugs for cancer-related pain . Of those prescribed analgesics , 63 % experienced breakthrough pain . In all , 69 % reported pain-related difficulties with everyday activities ; however , 50 % believed that their quality of life was not considered a priority in their overall care by their health care professional . CONCLUSIONS Across Europe and Israel , treatment of cancer pain is suboptimal . Pain and pain relief should be considered integral to the diagnosis and treatment of cancer ; management guidelines should be revised to improve pain control in patients with cancer In a double-blind , r and omised and parallel clinical trial , two oral doses of dipyrone ( 1 and 2 g ) administered every 8 h were compared with 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain . A total of 121 patients with cancer pain without gastric involvement participated in a 7-day treatment course and were allocated to receive either dipyrone 1 g ( n = 41 ) , dipyrone 2 g ( n = 38 ) or morphine ( n = 42 ) . Drug efficacy was analysed according to the degree of pain relief using a 100-mm visual analogue scale , and the number of patients who decided to increase the dose of the analgesic drug on day 4 . The analgesic effect of dipyrone , 2 g every 8 h , was similar to that of morphine . The efficacy of both schedules was significantly greater than that of dipyrone , 1 g every 8 h. Dipyrone at either 1 or 2 g doses tended to be better tolerated than morphine , although the differences were not statistically significant STUDY OBJECTIVE To compare the analgesic efficacy and safety of two single doses of ketorolac with diclofenac in acute cancer pain . DESIGN Double-blind , r and omized , clinical study . SETTING Hospital-based clinical research center . SUBJECTS One hundred eighty patients suffering acute , moderate , or severe cancer pain . INTERVENTIONS A single intramuscular injection of ketorolac 10 or 30 mg or diclofenac 75 mg . MEASUREMENTS AND MAIN RESULTS Pain intensity was assessed 30 minutes and 1 , 2 , 3 , 4 , 5 , and 6 hours after injection or until rescue drug administration . In approximately 70 % of patients all treatments provided prompt sustained pain relief throughout the 6-hour observation period . There were no statistically significant differences in any of the analyzed efficacy measures among the three groups . CONCLUSION Intramuscular ketorolac 10 mg is adequate to relieve cancer pain , and is equivalent to ketorolac 30 mg and to diclofenac 75 mg OBJECTIVE To compare the effectiveness of intravenous patient-controlled ( i.v.-PCA ) ketorolac to i.v.-PCA morphine in the treatment of postoperative pain in cancer patients . DESIGN In a double-blind , prospect i ve , r and omized trial , patients received either morphine in 1 mg/ml concentration or ketorolac 5 mg/ml for postoperative pain control . On arrival to the postanesthesia care unit ( PACU ) , the patients received 2 ml of medication every 5 min , until satisfactory analgesia was achieved . If pain persisted after 20 ml of study drug had been administered , 0.1 mg/kg morphine was given i.m . On discharge from the PACU , the patients were placed on an i.v.-PCA pump . All patients received a basal infusion of 1 ml/h with a 1-ml on-dem and bolus and a lockout interval of 10 min . Patients were offered 0.1 mg/kg morphine IM every 6 h , which they could refuse . SETTING University Cancer Center . PATIENTS Seventy patients scheduled for abdominal or truncal cancer operations . MAIN OUTCOME MEASURES Visual analog pain scores ( VAPS ) and Visual analog sedation scores ( VASS ) were used to measure the quality of pain control achieved either with ketorolac or morphine . The incidence of side effects was documented . RESULTS The VAPS were comparable between the groups . Patients in the ketorolac group requested more supplemental i.m . morphine . However , the total morphine dose and incidence of side effects was significantly higher in patients receiving i.v.-PCA morphine . CONCLUSIONS These results indicate that ketorolac supplemented with small doses of morphine is associated with a lower incidence of nausea , vomiting , and pruritus compared to morphine alone . This combination should be considered where immunosuppression from operation and administration of morphine is undesirable The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone . Diflunisal was given at the dosage of 500 mg perorally twice a day , and dipyrone was given at the dosage of 500 mg perorally three times a day . Duration of each treatment was 7 days ; after a 12-hour wash-out period , patients were given the other drug for another 7 days . A total of 50 patients were enrolled in the study . Pain intensity was assessed by 10-point visual analog scale ( VAS ) . Patients who had a VAS score higher than 5 were included . A total of 47 patients were evaluable . Initial VAS score was a mean of 8.57+/-1.33 . Diflunisal reduced the pain score by a mean of 4.65+/-3.10 , whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 ( p < 0.001 ) . Patients were also analyzed in three subgroups according to the presence of nonmetastatic , metastatic , and bone metastatic diseases . In each of these subgroups , diflunisal reduced the pain score more than dipyrone ; however , the difference was statistically significant only in patients who had bone metastasis . Adverse reactions were rare and acceptable with both drugs . Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain The analgesic effects of single oral doses of ketoprofen 100 and 300 mg , the combination of aspirin 650 mg plus codeine 60 mg , and placebo were compared under double-blind conditions in 160 hospitalized patients with cancer pain . At baseline and at 30 minutes and hourly for 6 hours after treatment , patients evaluated their pain intensity and pain relief . The 100 mg ketoprofen dose was significantly ( P less than 0.05 ) superior to placebo for all 14 derived efficacy parameters ; the 300 mg dose was significantly superior to placebo in all assessment s except derived onset of relief . Aspirin plus codeine was significantly ( P less than 0.05 ) superior to placebo for nine of the 14 assessment s. No statistically significant differences were observed among active treatments for any of the 14 derived parameters . The number of patients with a " good " response was greatest in the ketoprofen 100 mg group ( 55 % ) ; the numbers of good responders in the aspirin plus codeine ( 37.5 % ) and the ketoprofen 300 mg ( 30 % ) groups were comparable . The three active treatment groups were not significantly different from each other for patient response . The numbers of patients requiring rescue analgesic were significantly ( P less than 0.05 ) lower for both ketoprofen groups , but not for the aspirin plus codeine group , as compared with the placebo group . Twenty-three percent of the 160 patients reported adverse experiences , but there were no significant differences between the treatment groups in the number or type of experience . These results show that ketoprofen is as effective and well tolerated as aspirin plus codeine in relieving cancer pain The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established . However , the treatment of mild-to-moderate cancer pain is often limited to " as needed " dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic , which do not allow optimal titration of the individual components . This r and omized double-blind study was design ed to evaluate the efficacy of controlled-release codeine ( Codeine Contin ) in patients with cancer pain , and to estimate its dose equivalence to a st and ard combination of acetaminophen plus codeine . Twenty-four patients with at least moderate cancer pain were r and omized to Codeine Contin 100 , 200 , or 300 mg every 12 hr or acetaminophen plus codeine ( 600 mg/60 mg ) every 6 hr . On days 1 and 4 of dosing , pain intensity and pain relief were assessed hourly for 12 hr . The sum of pain intensity differences ( SPID ) from baseline and the total pain relief ( TOTPAR ) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4 , compared with day 1 . Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine ( 600 mg/60 mg ) given every 6 hr . Because a similar equivalence was also demonstrated from analysis of adverse event data , it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40 % lower dose of codeine provided by the combination . ( ABSTRACT TRUNCATED AT 250 WORDS & NA ; The analgesic efficacy and toxicity of oral diclofenac sodium 50 mg ( q.i.d . ) vs. nefopam 60 mg ( q.i.d . ) and a combination of 640 mg ASA and 40 mg codeine ( q.i.d . ) in cancer patients with moderate to severe chronic pain has been evaluated in a r and omized double‐blind study . Planned duration of treatment was 10 days . Pain intensity was evaluated by a visual analog scale . The length of patient participation in the trial , the patient 's final global evaluation and the incidence of side effects were also evaluated . Ninety‐nine patients were enrolled in the study . All treatments produced a statistically significant pain relief ( P < 0.01 ) without differences among groups but only 26 of 99 patients ( 26.3 % ) completed the planned treatment period . Mean time in the study was 4.65 days . Inefficacy and side effects were the main reasons for premature treatment interruption . Patients treated with nefopam had a significantly shorter period in the study than patients treated with the other 2 treatments . Adverse effects were slightly more frequent with the nefopam and ASA + codeine regimens . The 3 therapeutic regimens appear to be similar as to analgesic efficacy , but diclofenac presents the advantage of a slightly better safety profile than nefopam and the ASA + codeine combination It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids . 20 patients with malignant nerve pain were r and omly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week , followed by cross-over medication during the second week in a double-blind , double-dummy protocol . In the 16 evaluable patients , a significant ( P < 0.05 ) reduction of 26 % ( S.E. + /- 7.9 ) in pain intensity was reached at day 7 , compared to baseline pain . At day 7 , significant pain relief of 32 % ( P < 0.05 ) was observed in the naproxen group , but not in the morphine group ( 21 % , P = 0.14 ) . Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen . Additional pain relief could be observed in 4/9 patients with cross-over medication . These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids , and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief The efficacy and tolerability of acetylsalicylic acid , paracetamol , diclofenac , ibuprofen , indomethacin , pirprofen , sulindac , naproxen and suprofen were compared in the treatment of cancer pain . In a double-blind , within-patient r and omized study , each drug was given for 1 week to eight patients and for another week to a further eight patients . A total of 65 patients were effectively treated ; only 48 completed week 1 and 41 completed week 2 . Naproxen , diclofenac and indomethacin were highly effective in pain relief ( tested by means of a 100 mm visual analogue scale ) and were relatively well tolerated . It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind , balanced incomplete block design was adopted , in which each patient received two of the three test treatments , with an interval of 24 hours . Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug , and was superior to 1 g of the acetylsalicylic acid derivative in the patients ' assessment of the overall response . This was expressed by a visual analog scale and preferences . No adverse reaction was observed with any treatment In a r and omized single-blind study carried out simultaneously in five Departments for Pain Therapy and Palliative Care , the analgesic efficacy and side effects of oral ketorolac ( ketorolac tromethamine , Tora-Dol , CAS 74103 - 07 - 4 ) and diclofenac sodium were compared in a population of 100 advanced cancer patients suffering from somatic and /or visceral pain . The treatment was carried out in agreement with the first step of the WHO pharmacological strategy in cancer pain . The administered dosage was 10 mg every 6 h for ketorolac and 50 mg every 8 h for diclofenac sodium . The study showed the efficacy of both drugs in cancer pain . A greater number of keterolac patients could pass to the second WHO step later than diclofenac patients . As to the tolerability , both drugs turned out to be similar , except for " sleepiness " , which was four times more frequent ( p < 0.05 ) in the diclofenac group A r and omized double-blind trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug , ketorolac , in the treatment of cancer pain compared with the opioid pentazocine . A total of 40 patients with moderate to severe cancer pain were studied , 20 patients being treated with 10 mg ketorolac given orally every 6 h and 20 receiving 50 mg pentazocine given orally every 6 h for up to 7 days . A reduction in the severity of the pain was recorded in both treatment groups with no significant difference in efficacy being found between the two therapies , although withdrawals due to adverse reactions were significantly less in the ketorolac-treated group ( P < 0.005 ) . It is concluded that ketorolac may be a useful and more acceptable alternative to opioids in the treatment of cancer pain This r and omized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting , antiprostagl and in agent ibuprofen ( Motrin , Upjohn ) in 28 patients with moderate to severe cancer-related pain , who were already using a narcotic for pain relief . Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia , without concomitantly increasing side effects or euphoria Thirty subjects with chronic moderate to severe pain who were receiving oxycodone/acetaminophen ( oxy/APAP ) for analgesia were initially evaluated for at least 7 days for oxy/APAP requirements for pain control . Each subject then received , in a r and omized double‐blind fashion , either 600 mg ibuprofen or placebo for an additional 7 days while hospitalized . Oxy/APAP usage was recorded daily along with efficacy and toxicity parameters . Overall global evaluations were also recorded on completion of the study . Comparison of mean differences before and after treatment with ibuprofen or placebo indicated a marked decrease in oxy/APAP use with ibuprofen ( p < 0.01 ) and a slight increase in use in the placebo group . Reduction in oxy/APAP usage occurred within 24 hours and maximized at 5 days . Overall global scores showed a marked preference for the ibuprofen combination over placebo ( p < 0.01 ) . Daily pain intensity ( p < 0.05 ) and pain relief scores ( p < 0.05 ) also improved with the addition of ibuprofen . This study indicates that ibuprofen is efficacious in the management of chronic cancer pain , result ing in both enhanced analgesia and a reduction in concomitant narcotic use AIM To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug , ketorolac ( Toradol , Recordati spa , Milan ) 10 mg p.o . ( t.i.d . ) with diclofenac ( Voltaren , Novartis Farma , Origglo , VA ) 50 mg p.o . ( t.i.d . ) in cancer patients with moderate to severe chronic pain . METHODS AND STUDY DESIGN The study was a multicenter r and omized double-blind cross-over trial . Each treatment lasted 7 days , after which the patients crossed over to the other drug . Pain intensity was evaluated by the visual analogue scale ( VAS ) after the first dose and by the 5-point verbal rating scale ( VRS ) by the patient and by the physician following the 7-day treatment . RESULTS AND CONCLUSIONS A total of 138 advanced cancer patients were enrolled in the study . Overall 251 single-dose administrations ( 117 cross-over observations ) and 257 multiple treatments ( 127 cross-over experiments ) were assessable . After a single administration of ketorolac and diclofenac , no significant difference could be observed in analgesic activity , as indicated by the area under the pain-intensity time curve ( AUC0 - 8 ) , in the maximum efficacy , or the duration of efficacy of the two drugs . The Westlake confidence intervals of the AUC0 - 8 ratio ( ketorolac : diclofenac ) ( 1.07 ; 90 % CI , 0.94 - 1.19 ) , of the maximum efficacy ratio ( 1.03 ; 90 % CI , 0.92 - 1.14 ) , and the duration of efficacy ratio ( 1.05 ; 90 % CI , 0.97 - 1.11 ) showed the bioequivalence of the two drugs . Satisfactory pain relief was reported for multiple 7-day treatments , with no significant differences between the two therapies : according to the physician 's evaluation , in 93/128 ( 73 % ; 95 % CI , 65 - 80 % ) ketorolac treatments and 91/129 ( 71 % ; 95 % CI , 63 - 78 % ) diclofenac treatments ; according to the patient 's evaluation , in 83/128 cases ( 65 % ; 95 % CI , 57 - 73 % ) after ketorolac and in 74/129 cases ( 57 % ; 95 % CI , 49 - 66 % ) after diclofenac . Adverse symptoms were acceptable with both drugs . Interestingly , a pronounced sequence effect was found : gastric disturbances after ketorolac were observed mainly ( 10 out of 15 observed events ) when the drug was given to patients pretreated with diclofenac OBJECTIVES By removing systematic differences across treatment groups , simple r and omization is assumed to protect against bias . However , r and om differences may remain if the sample size is insufficiently large . We sought to determine the minimal sample size required to eliminate r and om differences , thereby allowing an unbiased estimation of the treatment effect . STUDY DESIGN AND SETTING We reanalyzed two published multicenter , large , and simple trials : the International Stroke Trial ( IST ) and the Coronary Artery Bypass Grafting ( CABG ) Off- or On-Pump Revascularization Study ( CORONARY ) . We reiterated 1,000 times the analysis originally reported by the investigators in r and om sample s of varying size . We measured the covariates balance across the treatment arms . We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke ( IST ) , and the effect of off-pump CABG on a composite primary outcome of death , nonfatal stroke , nonfatal myocardial infa rct ion , or new renal failure requiring dialysis at 30 days ( CORONARY ) . In addition , we conducted a series of Monte Carlo simulations of r and omized trials to supplement these analyses . RESULTS R and omization removes r and om differences between treatment groups when including at least 1,000 participants , thereby result ing in minimal bias in effects estimation . Later , substantial bias is observed . In a short review , we show such an enrollment is achieved in 41.5 % of phase 3 trials published in the highest impact medical journals . CONCLUSIONS Conclusions drawn from completely r and omized trials enrolling a few participants may not be reliable . In these circumstances , alternatives such as minimization or blocking should be considered for allocating the treatment Seventy-five patients with moderate to severe cancer pain were r and omly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally , acetaminophen 600 mg plus codeine 60 mg orally , or placebo , followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days . Patient characteristics were similar among the treatment groups . The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief . Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine , although there were no differences in mean daily ratings of overall effects for either study medication . Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine . We conclude that ketorolac has significant analgesic activity in patients with cancer pain , although its precise role in the treatment regimen of these patients remains undefined In a multicentric , interindividual , double-blind study , the analgesic action , duration of effect , tolerability and side effects of the new combination preparation , Combaren ( diclofenac-Na 50 mg+codeine phosphate 50 mg ) , were compared with those of diclofenac-Na 50 mg ( Voltaren 50 ) in 184 patients with severe tumor-related pain . The results show that Combaren is a highly effective preparation for the treatment of severe tumor pain . The combination of diclofenac-Na with codeine phosphate leads to a clear , statistically significant , augmentation of the effectiveness of additionally used analgesics on pain severity , and the general effectiveness of the combination is more positively assessed that that of monotherapy with diclofenac ( also effective ) . In the staged approach to the treatment of malignancy-related pain in which the aim is to provide continuous , preventive analgesia rather than ad hoc treatment of newly developing or worsening pain , this combination preparation will presumably find a permanent place in stage I/II of the generally accepted staged pain-treatment scheme Summary 64 patients with pain associated with advanced cancer were treated with either nimesulide or diclofenac as initial analgesia . Patients were r and omly allocated to 1 of 4 treatment groups : oral nimesulide 300 mg/day ; oral diclofenac 150 mg/day ; rectal nimesulide 400 mg/day ; and rectal diclofenac 200 mg/day . After 1 week of treatment , both drugs provided an adequate degree of pain relief and allowed an increase in sleep duration . There were no significant differences in efficacy between the drugs or routes of administration . Fewer side effects were observed with nimesulide , giving this agent a better therapeutic index than the reference compound This double-blind , placebo controlled study compared the analgesic efficacy of piroxicam with acetylsalicylic acid ( ASA ) in patients having continuous pain with advanced head and neck cancers . They were r and omly divided into two groups of 25 patients each ; 36 of these 50 patients completed the study . After four days of treatment , there was a significant reduction in a modified numerical rating scale ( NRS ) of pain in the piroxicam group as well as in the ASA group . There was a concomitant increase in the hours of sleep in the piroxicam group and in the ASA group . The decrease in NRS and the increase in sleeping hours was not statistically significantly different between the two groups . Patients receiving piroxicam had a low incidence of upper gastrointestinal side-effects compared with those receiving ASA . The results of this study suggest that piroxicam can be used as first line treatment in place of ASA in patients with head and neck cancers suffering from moderate to severe pain . The advantages are less frequent dosing , better patient compliance and few side-effects Summary The effectiveness of diclofenac 50 mg t.i.d . as additive treatment to parenteral patient-controlled administration therapy ( PCAT ) with morphine in cancer pain has been investigated in a double-blind study . In the fifteen patients who completed the study , morphine i.v . was titrated to optimal pain relief over 5 days . The mean total morphine consumption was significantly reduced during diclofenac administration ( 82.8 mg morphine per day ) compared to placebo ( 95.0 mg morphine per day ) . The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine . Pain , self-assessed according to VAS , tended to be lower during the diclofenac period , although the difference did not reach statistical significance . No adverse events were recorded among the 15 patients who completed the study .The present findings show that a non-steroidal anti-inflammatory agent , such as diclofenac , has a morphine-sparing effect in morphine-treated patients with cancer pain A double-blind study of analgesic drug combinations was conducted , involving 100 patients with pain due to cancer . The combinations of 650 mg of aspirin plus either 65 mg of codeine , 9.76 mg of oxycodone , or 25 mg of pentazocine hydrochloride each produced significantly greater pain relief than aspirin alone . Side effects for a single dose of these effective combinations were essentially equal and clinical ly tolerable . The combinations of 650 mg of aspirin plus either 65 mg of caffeine , 32 mg of pentobarbital sodium , 25 mg of promazine hydrochloride , 75 mg of ethoheptazine citrate , or 100 mg of propoxyphene napsylate did not show significant advantage in analgesic effect over aspirin alone . ( JAMA 229:55 - 59 , 1974 The analgesic efficacy of naproxen ( 500 mg / 12 h ) and aspirin ( 600 mg / 4 h ) in 28 patients with advanced malignant disease was assessed in a r and omized , double-blind , cross-over study of two weeks ’ duration . Efficacy was assessed using severity of pain ( linear analogue self- assessment ) , pain score ( McGill Pain Question naire ) , pain severity , and time of onset of pain relief . Both analgesics provided equal , highly effective relief of pain . It is concluded that naproxen is a useful addition to the analgesics available for patients with advanced malignant disease and has the advantage of 12-h rather than 4-h dosage In a single-blind r and om study , simultaneously carried out by five Pain Therapy and Palliative Care Centres , the analgesic power and side-effects of sodium naproxen ( CAS 26159 - 34 - 2 ) and sodium diclofenac ( CAS 15307 - 86 - 5 ) by mouth were compared in a group of 100 advanced cancer patients . The patients complained of somatic and /or visceral pain and were treated with non-steroid anti-inflammatories as required . The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac . The study stressed the similar analgesic effect of the two drugs -- pain intensity and duration decreased by half in the first week of treatment-- and a comparatively low morbidity rate Evaluation of the analgesic activity of indoprofen was carried out in patients with cancer pain under double‐blind conditions and compared with aspirin and placebo . A r and omized experimental design was followed . Single oral doses were given of the test drug ( 100 and 200 mg ) , aspirin ( 600 and 1,000 mg ) , and placebo . For measuring analgesia , 5‐point pain intensity and pain relief semiquantitative scales were used . Potency ratio between drugs was calculated on SPID ( sum of pain intensity differences ) and TOTPAR ( total pain relief ) and result ed in 10.3 by combination of estimates . In a group of only 24 patients , the data supported the following conclusions : indoprofen at 100 and 200 mg single doses is effective in relieving cancer pain ; it displays a dose‐related analgesic effect comparable to that of aspirin with only one‐tenth the dose |
598 | 25,011,987 | PH was consistently associated with increased mortality risk in all forms of LHD , except for aortic valve disease where findings were inconsistent .
CONCLUSIONS PH is almost invariably associated with increased mortality risk in patients with LHD . | OBJECTIVES Left heart disease ( LHD ) is the main cause of pulmonary hypertension ( PH ) , but little is known regarding the predictors of adverse outcome of PH associated with LHD ( PH-LHD ) .
We conducted a systematic review to investigate the predictors of hospitalisations for heart failure and mortality in patients with PH-LHD . | Background —Pulmonary hypertension is a clinical ly useful predictor of death in patients with heart failure . Whether pulmonary hypertension has the same prognostic value among specific underlying causes of cardiomyopathy is unknown . Using a diverse cohort of cardiomyopathy patients , we tested the hypotheses that ( 1 ) elevated mean pulmonary arterial pressure is the most important hemodynamic predictor of death and ( 2 ) the prognostic value of mean pulmonary pressure varies among different cardiomyopathies . Methods and Results — Patients ( n=1134 ) with new cardiomyopathy were prospect ively assigned a specific diagnosis on the basis of clinical evaluation and endomyocardial biopsy . All patients underwent right heart catheterization at baseline and were followed for an average of 4.4 years . In multivariate Cox models that allowed for nonlinear relations between hemodynamics and death , mean systemic pressure ( mSP ) and mean pulmonary arterial pressure ( mPA ) emerged as the most important hemodynamic predictors of death . Moreover , there was a statistically significant positive interaction between mPA and the diagnosis of myocarditis . For each 5–mm Hg increase in baseline mSP , mortality rates decreased with relative hazard ( RH ) of 0.89 ( 0.86 to 0.92 ) . For a 5–mm Hg increase in baseline mPA , mortality rates increased in patients who did not carry the diagnosis of myocarditis with RH 1.23 ( 1.17 to 1.29 ) ; among patients with myocarditis , mortality rates increased substantially with RH of 1.85 ( 1.50 to 2.29;P < 0.001 for interaction ) . Conclusions —Baseline mPA is particularly important for stratifying risk in myocarditis . These findings suggest that secondary pulmonary hypertension may have different biological features in myocarditis and that patients with pulmonary hypertension and myocarditis should be targeted for aggressive medical therapy 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 Acute heart failure ( AHF ) in sub-Saharan Africa has not been well characterized . Therefore , we sought to describe the characteristics , treatment , and outcomes of patients admitted with AHF in sub-Saharan Africa . METHODS The Sub-Saharan Africa Survey of Heart Failure ( THESUS-HF ) was a prospect i ve , multicenter , observational survey of patients with AHF admitted to 12 university hospitals in 9 countries . Among patients presenting with AHF , we determined the causes , treatment , and outcomes during 6 months of follow-up . RESULTS From July 1 , 2007 , to June 30 , 2010 , we enrolled 1006 patients presenting with AHF . Mean ( SD ) age was 52.3 ( 18.3 ) years , 511 ( 50.8 % ) were women , and the predominant race was black African ( 984 of 999 [ 98.5 % ] ) . Mean ( SD ) left ventricular ejection fraction was 39.5 % ( 16.5 % ) . Heart failure was most commonly due to hypertension ( n = 453 [ 45.4 % ] ) and rheumatic heart disease ( n = 143 [ 14.3 % ] ) . Ischemic heart disease ( n = 77 [ 7.7 % ] ) was not a common cause of AHF . Concurrent renal dysfunction ( estimated glomerular filtration rate , < 30 mL/min/173 m(2 ) ) , diabetes mellitus , anemia ( hemoglobin level , < 10 g/dL ) , and atrial fibrillation were found in 73 ( 7.7 % ) , 114 ( 11.4 % ) , 147 ( 15.2 % ) , and 184 cases ( 18.3 % ) , respectively ; 65 of 500 patients undergoing testing ( 13.0 % ) were seropositive for the human immunodeficiency virus . The median hospital stay was 7 days ( interquartile range , 5 - 10 ) , with an in-hospital mortality of 4.2 % . Estimated 180-day mortality was 17.8 % ( 95 % CI , 15.4%-20.6 % ) . Most patients were treated with renin-angiotensin system blockers but not β-blockers at discharge . Hydralazine hydrochloride and nitrates were rarely used . CONCLUSIONS In African patients , AHF has a predominantly nonischemic cause , most commonly hypertension . The condition occurs in middle-aged adults , equally in men and women , and is associated with high mortality . The outcome is similar to that observed in non-African AHF registries , suggesting that AHF has a dire prognosis globally , regardless of the cause BACKGROUND Prognostic implication s of echocardiographic assessment of pulmonary hypertension ( PH ) in non-selected patients hospitalized for acute heart failure ( AHF ) are not clearly defined . The aim of this study was to evaluate the association between echocardiography-derived PH in AHF and 1-year all-cause mortality . METHODS We prospect ively included 1210 consecutive patients admitted for AHF . Patients with significant heart valve disease were excluded . Pulmonary arterial systolic pressure ( PASP ) was estimated using transthoracic echocardiography during hospitalization ( mean time after admission 96±24h ) . Patients were categorized as follows : non-measurable , normal PASP ( PASP≤35mmHg ) , mild ( PASP 36 - 45mmHg ) , moderate ( PASP 46 - 60mmHg ) and severe PH ( PASP > 60mmHg ) . The independent association between PASP and 1-year mortality was assessed with Cox regression analysis . RESULTS At 1-year follow-up , 232 ( 19.2 % ) deaths were registered . PASP was measured in 502 ( 41.6 % ) patients with a median of 46 [ 38 - 55 ] mmHg . The distribution of population was : 708 ( 58.5 % ) , 76 ( 6.3 % ) , 147 ( 12.1 % ) , 190 ( 15.7 % ) and 89 ( 7.4 % ) for non-measurable , normal PASP , mild , moderate and severe PH , respectively . One-year mortality was lower for patients with normal PASP ( 1.32 per 10 person-years ) , intermediate for patients with non-measurable , mild and moderate PH ( 2.48 , 2.46 and 2.62 per 10 persons-year , respectively ) and higher for those with severe PH ( 4.89 per 10 person-years ) . After multivariate adjustment , only patients with PASP > 60mmHg displayed significant adjusted increase in the risk of 1-year all-cause mortality , compared to patients with normal PASP ( HR=2.56 ; CI 95 % : 1.05 - 6.22 , p=0.038 ) . CONCLUSIONS In AHF , severe pulmonary hypertension derived by echocardiography is an independent predictor of 1-year-mortality Objective To evaluate the predictors of pulmonary artery systolic pressure ( PASP ) in organic mitral regurgitation ( MR ) and its prognostic value after surgery . Design Prospect i ve observational study , conducted from 1998 to 2006 . Setting Echocardiography and cardiac surgery departments , University Hospital . Patients Echocardiography was carried out in 256 patients ( 63±12 years , 170 male ) with organic MR ( degenerative aetiology : 91 % ) referred for surgery . Main outcome measures Echocardiography predictors of PASP . Postoperative end points were overall mortality and cardiovascular mortality . Results Baseline PASP was 45±14 mmHg , ranging from 25 to 105 mmHg . PASP was ≥50 mmHg in 82 patients ( 32 % ) . Left atrial volume ( p=0.003 ) , mitral deceleration time ( p<0.0001 ) and mitral medial E/E′ ( p<0.0001 ) were independent predictors of PASP , whereas left ventricular size and systolic function were not predictors . Mitral valve repair was performed in 194 patients ( 76 % ) and mitral valve replacement in 62 ( 24 % ) . In a Cox model mitral valve repair ( HR=0.41 ( 95 % CI 0.20 to 0.85 ) , p=0.016 ) and PASP ( HR=1.43 ( 95 % CI 1.09 to 1.88 ) per 10 mmHg increment , p=0.011 ) were independent predictors of overall mortality , even after adjustment for known predictors . PASP ( HR=1.49 ( 95 % CI 1.03 to 2.16 ) per 10 mmHg increment , p=0.033 ) was also an independent predictor of cardiac mortality . Eight-year survival after surgery was 58.6 % and 86.6 % in patients with baseline PASP ≥50 mmHg or < 50 mmHg , respectively ( p<0.0001 ) . Conclusions In organic MR , mitral deceleration time , mitral E/E′ and left atrial volume correlate with PASP . Pulmonary artery systolic pressure ≥50 mmHg is an independent predictor of overall and cardiovascular mortality after surgery in organic MR BACKGROUND AND AIM OF THE STUDY The prevalence of severe pulmonary hypertension ( PH ) in patients with severe mitral stenosis ( MS ) remains unknown , and the long-term effect of mitral balloon valvotomy ( MBV ) in large numbers of these patients is not well characterized . METHODS Details from the prospect i ve MBV data base at the authors ' institution relating to 559 consecutive patients who had successful MBV were analyzed . Patients were allocated to three groups on the basis of their pulmonary artery systolic pressure ( PASP ) at cardiac catheterization immediately before MBV : group A ( n = 345 ) had PASP < 50 mmHg ; group B ( n = 183 ) had PASP 50 - 79 mmHg ; and group C ( n = 31 ) had PASP > or = 80 mmHg . Patients were evaluated clinical ly and echocardiographically at six months after MBV , and annually thereafter for up to 13 years . RESULTS No mortality was encountered after MBV . Immediately after MBV , the mean PASP was 38.5+/-6.8 mmHg in group A ( mild PH ) , 59.0+/-7.7 mmHg in group B ( moderately severe PH ) , and 97.8+/-17.0 mmHg in group C ( severe PH ) . At follow up ( ca . 4 years ) , Doppler-monitored PASP fell to normal , and was similar in groups A , B and C ( 29+/-8 , 31+/-9 , and 29+/-5 mmHg , respectively ; p = NS ) . CONCLUSION MBV was shown to be safe and effective in treating patients with MS and severe PH . The latter condition regressed to normal levels over 6 - 12 months after successful MBV OBJECTIVES The purpose of this study was to determine among community patients with heart failure ( HF ) whether pulmonary artery systolic pressure ( PASP ) assessed by Doppler echocardiography was associated with death and improved risk prediction over established factors , using the integrated discrimination improvement and net reclassification improvement . BACKGROUND Although several studies have focused on idiopathic pulmonary arterial hypertension , less is known about pulmonary hypertension among patients with HF , particularly about its prognostic value in the community . METHODS Between 2003 and 2010 , Olmsted County residents with HF prospect ively underwent assessment of ejection fraction , diastolic function , and PASP by Doppler echocardiography . RESULTS PASP was recorded in 1,049 of 1,153 patients ( mean age 76 ± 13 ; 51 % women ) . Median PASP was 48 mm Hg ( 25th to 75th percentile : 37.0 to 58.0 ) . There were 489 deaths after a follow-up of 2.7 ± 1.9 years . There was a strong positive grade d association between PASP and mortality . Increasing PASP was associated with an increased risk of death ( hazard ratio [ HR ] : 1.45 , 95 % confidence interval [ CI ] : 1.13 to 1.85 for tertile 2 ; HR : 2.07 , 95 % CI : 1.62 to 2.64 for tertile 3 vs. tertile 1 ) , independently of age , sex , comorbidities , ejection fraction , and diastolic function . Adding PASP to models including these clinical characteristics result ed in an increase in the c-statistic from 0.704 to 0.742 ( p = 0.007 ) , an integrated discrimination improvement gain of 4.2 % ( p < 0.001 ) , and a net reclassification improvement of 14.1 % ( p = 0.002 ) , indicating that PASP improved prediction of death over traditional prognostic factors . All results were similar for cardiovascular death . CONCLUSIONS Among community patients with HF , PASP strongly predicts death and provides incremental and clinical ly relevant prognostic information independently of known predictors of outcomes |
599 | 18,945,379 | RESULTS Statistically significant effect sizes were found for all working memory measures , indicating deficits in schizophrenia groups .
Meta-regression analyses showed that the working memory deficit was not simply explained by discrepancies in current IQ between schizophrenia and control groups .
CONCLUSIONS Large deficits in working memory were demonstrated in schizophrenia groups across all three working memory domains .
There were , however , no clear differences across subdomains or between particular working memory tasks . | BACKGROUND Memory impairment is being recognized increasingly as an important feature of the neuropsychology of schizophrenia .
Dysfunction of working memory , a system for the short-term storage and manipulation of information , may relate to a number of core symptoms of schizophrenia .
Many studies have examined working memory function in schizophrenia but a clear underst and ing of the nature and extent of any deficit has been elusive . | Background Prospect i ve memory ( PM ) , the act of remembering that something has to be done in the future without any explicit prompting to recall , provides a useful framework with which to examine problems in internal- source monitoring . This is because it requires distinguishing between two internally-generated processes , namely the intention to perform an action versus actual performance of the action . In habitual tasks , such as taking medicine every few hours , the same PM task is performed regularly and thus it is essential that the individual is able to distinguish thoughts ( i.e. , thinking about taking the medicine ) from actions ( i.e. , actually taking the medicine ) . Methods We assessed habitual PM in patients with schizophrenia by employing a laboratory analogue of a habitual PM task in which , concurrently with maneuvering a ball around an obstacle course ( ongoing activity ) , participants were to turn over a counter once during each trial ( PM task ) . After each trial , participants were asked whether they had remembered to turn the counter over . Results Patients with schizophrenia made a disproportionate number of errors compared to controls of reporting that a PM response had been made ( i.e. , the counter turned over ) after an omission error ( i.e. , the counter was not turned over ) . There was no group difference in terms of reporting that an omission error occurred ( i.e. , forgetting to turn over the counter ) when in fact a PM response had been made . Conclusion Patients with schizophrenia displayed a specific deficit distinguishing between two internally-generated sources , attributable to either poor source monitoring or temporal discrimination Working memory may be conceptualized as a multi-component system involving the active maintenance and manipulation of stored information in the service of planning/guiding behaviour . Impaired spatial working memory is a robust finding in schizophrenia patients which has been related to an impairment in frontostriatal connectivity . The purpose of this study was to examine the specificity of this impairment by comparing the mnemonic and executive aspects of working memory performance in schizophrenia and bipolar disorder with psychotic features , focusing particularly on the functional dynamics between task components . Twenty-four patients with schizophrenia , 14 patients with bipolar I disorder ( manic phase ) and 33 healthy control subjects were assessed using the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) : including the spatial working memory ( between search errors and strategy scores ) spatial span ( storage capacity ) and spatial planning ( Stockings of Cambridge : accuracy and latency ) tasks . Both patient groups were impaired on the spatial span task , which requires the maintenance and retrieval of stored information . In contrast , only schizophrenia patients showed a significant deficit in between search errors , which requires both maintenance and manipulation of information in working memory . That is , they exhibited both a mnemonic and an executive dysfunction . Spatial span was particularly important to accurate planning ability in bipolar patients . In contrast , in patients with schizophrenia poor spatial working memory was a significant predictor of planning impairments , consistent with failures in goal selection , evaluation and /or execution . Furthermore , initial planning time was positively correlated with the latency to complete a planning sequence . This pattern of slow cognitive processing in schizophrenia patients only , resembled that reported previously in patients with basal ganglia disorders . These findings are discussed in terms of a possible common disturbance in fronto-parietal circuitry in the two disorders together with a specific disturbance of fronto-striatal circuitry in schizophrenia , that is not present in bipolar disorder There is accumulating evidence for involvement of the prefrontal cortex ( PFC ) in the pathophysiology of schizophrenia . A primary function supported by the PFC is working memory ( WM ) . Findings from WM studies in schizophrenia can provide insight into the nature of clinical symptoms and cognitive deficits associated with this disorder , as well as begin to suggest areas of underlying neuropathology . To date , studies have not adequately investigated different WM domains ( e.g. , verbal , spatial , or object ) or processing requirements ( e.g. , maintenance , monitoring , or manipulation ) , shown to be associated with distinct patterns of neural activation , in schizophrenia patients and their well relatives . Accordingly , this study evaluated the performance of schizophrenia patients , their first-degree biological relatives , and nonpsychiatric controls on a comprehensive battery of WM tasks and investigated the association among WM deficits and schizophrenia-spectrum psychopathology . The findings indicate that schizophrenia patients are consistently impaired on WM tasks , irrespective of WM domain or processing requirements . In contrast , their unaffected relatives are only impaired on WM tasks with higher central executive processing requirements . This pattern of WM performance may further implicate DLPFC dysfunction in the liability for schizophrenia and has implication s for future cognitive , genetic , and neurodevelopmental research The purpose of this study was to investigate basal ganglia ( BG ) and medial temporal lobe ( MTL ) dependent learning in patients with schizophrenia . Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent ( if two stimuli are associated with the same response ) increases generalization between them . The learning of stimulus-response pairs is related to the BG , whereas the MTL system participates in stimulus generalization . Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated . Volunteers received the Rutgers acquired equivalence task ( face-fish task ) by [ Myers , C.E. , Shohamy , D. , Gluck , M.A. et al. , 2003 . Dissociating hippocampal versus basal ganglia contributions to learning and transfer . J. Cogn . Neurosci . 15 , 185 - 193 . ] , the California Verbal Learning Test ( CVLT ) , and the n-back working memory test . The Rutgers acquired equivalence task investigates BG-dependent processes ( stimulus-response learning ) and MTL-dependent processes ( stimulus generalization ) with a single test . Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization , whereas stimulus-response learning was spared . The stimulus generalization deficit correlated with the CVLT performance ( total scores from trials 1 - 5 and long-delay recall ) , but not with the n-back test performance . The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics . In conclusion , this is the first study to show that patients with schizophrenia exhibit deficits during MTL-dependent learning , but not during BG-dependent learning within a single task . High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-stiratal system Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents , healthy humans , and individuals with dementia of the Alzheimer 's type . In this study , patients with schizophrenia , healthy control subjects , and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin ( for " taste " ) or 23.7 mg saccharin alone , followed by cognitive testing on a complex battery . At this glucose dose , verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia ; this effect was not detected in either the psychiatric or normal controls . The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability Controls ( N = 45 ) , schizophrenics ( N = 20 ) and alcoholics ( N = 23 ) were asked to choose at r and om a number between 1 and 10 , 100 times . The correlation matrices of five different r and omization indices were used to study within group variation ; these matrices were similar for the normal and alcoholic groups , but very different for the schizophrenic group . The differences between the three groups were studied by canonical analysis and , in terms of the canonical variables , the mean performance of the normal group is clearly discriminated from that of the alcoholic and schizophrenic subjects To characterize the deficit in r and om number generation in schizophrenia with respect to control of sensory information processing , the present study employed a r and om number generation task using 10 digits ( 0 to 9 ) and compared two response modes ( oral and written ) with different amounts of sensory availability about the previous choices of the subject . Analysis indicated that the increased availability of previous information in the written response mode may exacerbate an aspect of the deficit in r and om number generation in schizophrenia reflecting the disturbance in control of sensory information processing . The comparison of performance in written and oral response modes may be useful in assessing schizophrenic psychopathology Patients with first-episode ( FE ) schizophrenia ( n=40 ) , with chronic schizophrenia ( n=40 ) and healthy controls ( n=40 ) matched for age , gender , education and parental socioeconomic status were administered a battery of st and ardized neuropsychological ( NP ) tests . Both patient groups showed generalized impairment relative to controls and the most pronounced deficits in visual-motor processing and attention ( VSM ) . Compared with FE patients , chronic schizophrenics performed worse in VSM and abstract ion/flexibility . Our findings suggest that NP deficits are fundamental manifestations of the illness , and that mainly frontally based dysfunctions are more prominent in chronic , kraepelinian patients The functioning of working memory in schizophrenic patients according to Baddeley 's model was examined in two complementary experiments . Experiment 1 comprised 27 patients and their controls , matched in age and level of education . Of this pool , 20 pairs participated also in Experiment 2 . Digit span , reading rate , and immediate serial recall assessed the functioning of the phonological loop . Corsi and pattern span tasks assessed the capacity of visuo-spatial memory . The central executive 's ability to monitor two concurrent tasks was evaluated in a dual task paradigm , and its capacity to control action in a r and om generation task . A preliminary set of analyses showed that the patients ' performances were reduced in all tasks explored , except in digit span . This initial pattern changed consistently after controlling for reading rate . While slow and fast reading patients were comparable in demographic and clinical criteria , slow reading patients showed impaired performance in all tasks , whereas fast reading patients exhibited reduced performance in visuo-spatial tasks and in the r and om generation task only . The state of functioning of working memory in schizophrenia appears , therefore , to vary consistently among the components of the model and is markedly impaired in slow reading patients . The implication s of slowness are discussed Objective : Atypical neuroleptics seem to be more beneficial than typical ones with respect to long-term neuropsychological functioning . Thus , most studies focus on the long-term effects of neuroleptics . We were interested in whether atypical neuroleptic treatment is also superior to typical drugs over relatively short periods of time . Methods : We studied 20 schizophrenic patients [ 10 males , mean age 35.5 years , mean Brief Psychiatric Rating Scale ( BPRS ) score at entry 58.9 ] admitted to our hospital with acute psychotic exacerbation . Nine of them were treated with typical and 11 with atypical neuroleptics . In addition , 14 healthy drug-free subjects ( 6 males , mean age 31.2 years ) were enrolled in the study and compared to the patients . As neuropsychological tools , a divided attention test , the Vienna reaction time test , the Benton visual retention test , digit span and a Multiple Choice Word Fluency Test ( MWT-B ) were used during the first week after admission , within the third week and before discharge ( approximately 3 months ) . Results : Patients scored significantly worse than healthy controls on nearly all tests ( except Vienna reaction time ) . Clinical ratings [ BPRS and Positive and Negative Symptom Scale for Schizophrenia ( PANSS ) ] improved markedly ( p < 0.01 ) , without a significant difference between typical and atypical medication . Clinical improvement ( PANSS total score ) correlated with less mistakes on the Benton test ( r = 0.762 , p = 0.017 ) and an improvement on the divided attention task ( r = 0.705 , p = 0.034 ) . Neuropsychological functioning ( explicit memory , p < 0.01 ; divided attention , p < 0.05 ) moderately improved for both groups under treatment but without a significant difference between atypical and typical antipsychotic drugs . Conclusions : Over short periods of time ( 3 months ) , neuropsychological disturbances in schizophrenia seem to be moderately responsive to both typical and atypical neuroleptics Twenty-six patients with schizophrenia and 12 patients with schizophrenia-like psychosis of epilepsy ( SLPE ) were compared to 38 healthy volunteers and 12 nonpsychotic patients with epilepsy to determine the contribution of psychosis to the pattern of cognition . Tests of memory and executive function were used . The schizophrenic group was more cognitively impaired than the SLPE and comparison groups . The profile of neuropsychological impairment in SLPE resembled that of schizophrenia and is unlikely to be explained solely by temporal lobe dysfunction . These results do not support the concept of SLPE as an independent nosological entity BACKGROUND The role of the inhibitory neurotransmitter gamma aminobutyric acid ( GABA ) in schizophrenia has previously been investigated using postmortem material . Recently , using single photon emission tomography ( SPET ) with the selective benzodiazepine antagonist 123I-Iomazenil as the radiolig and , we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia . The present study aim ed to build on this using the same in vivo scanning techniques , and relating findings to cognitive functioning . METHODS Ten nonpsychiatric control subjects and 15 schizophrenic patients , matched for age and h and edness , were scanned . A battery of neuropsychologic tests was also administered . RESULTS Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance , in the schizophrenic group compared to the control group . CONCLUSIONS Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning , involving memory and visual attention processes , in the schizophrenic group but not in the control group . A role for GABA in the pathophysiology of schizophrenia is suggested . Limitations of the present study and suggestions for future research are discussed The catechol-O-methyl transferase ( COMT ) gene is considered a leading schizophrenia c and i date gene . Although its role in increasing schizophrenia susceptibility has been conflicting , recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia . V158 M COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls . The effects of COMT genotype on four measures of working memory/executive functions ( Wisconsin Card Sorting , digit span backward , Trail Making and N-back tests ) and on MRI frontal brain volumes were examined . Genotype distributions were not significantly different between patients and controls . There were no significant genotype or genotype-by-group effects on any working memory/executive function measures . No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes . R and omization analyses using [15O]H2O positron emission tomography ( PET ) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task . Overall , these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function . Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified . A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period . A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points . At baseline , a generalized deficit across cognitive domains was evident for the schizophrenia sample . After 6 weeks of treatment , patients showed modest improvements in visual memory and visual perception , but a decline in verbal memory . Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period . Relatively static and generalized neuropsychological dysfunction , evident from illness onset , is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia |
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